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Sample records for co-activator pcaf regulates

  1. PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α

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    Cheng Sun

    2014-12-01

    Full Text Available PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes.

  2. The epigenetic factor PCAF regulates vascular inflammation and is essential for intimal hyperplasia development.

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    Rob C M de Jong

    Full Text Available Genetic P300/CBP-associated factor (PCAF variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia.PCAF contribution to inflammation and intimal hyperplasia was assessed in leukocytes, macrophages and vascular smooth muscle cells (vSMCs in vitro and in a mouse model for intimal hyperplasia, in which a cuff is placed around the femoral artery. PCAF deficiency downregulate CCL2, IL-6 and TNF-alpha expression, as demonstrated on cultured vSMCs, leukocytes and macrophages. PCAF KO mice showed a 71.8% reduction of vSMC-rich intimal hyperplasia, a 73.4% reduction of intima/media ratio and a 63.7% reduction of luminal stenosis after femoral artery cuff placement compared to wild type (WT mice. The association of PCAF and vascular inflammation was further investigated using the potent natural PCAF inhibitor garcinol. Garcinol treatment reduced CCL2 and TNF-alpha expression, as demonstrated on cultured vSMCs and leukocytes. To assess the effect of garcinol treatment on vascular inflammation we used hypercholesterolemic ApoE*3-Leiden mice. After cuff placement, garcinol treatment resulted in reduced arterial leukocyte and macrophage adherence and infiltration after three days compared to untreated animals.These results identify a vital role for the lysine acetyltransferase PCAF in the regulation of local inflammation after arterial injury and likely the subsequent vSMC proliferation, responsible for intimal hyperplasia.

  3. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation

    DEFF Research Database (Denmark)

    Malatesta, Martina; Steinhauer, Cornelia; Mohammad, Faizaan

    2013-01-01

    The Hedgehog (Hh) signaling pathway plays an important role in embryonic patterning and development of many tissues and organs as well as in maintaining and repairing mature tissues in adults. Uncontrolled activation of the Hh-Gli pathway has been implicated in developmental abnormalities as well...... that the histone acetyltransferase PCAF/KAT2B is an important factor of the Hh pathway. Specifically, we show that PCAF depletion impairs Hh activity and reduces expression of Hh target genes. Consequently, PCAF downregulation in medulloblastoma and glioblastoma cells leads to decreased proliferation and increased...... apoptosis. In addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh-Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh target gene promoters. Finally, we observed that PCAF silencing reduces the tumor-forming potential of neural stem cells...

  4. PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

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    Meimei Zhao

    2017-08-01

    Full Text Available The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.

  5. miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells

    International Nuclear Information System (INIS)

    Gong, Ai-Yu; Eischeid, Alex N; Xiao, Jing; Zhao, Jian; Chen, Dongqing; Wang, Zhao-Yi; Young, Charles YF; Chen, Xian-Ming

    2012-01-01

    Androgen receptor (AR) signalling is critical to the initiation and progression of prostate cancer (PCa). Transcriptional activity of AR involves chromatin recruitment of co-activators, including the p300/CBP-associated factor (PCAF). Distinct miRNA expression profiles have been identified in PCa cells during the development and progression of the disease. Whether miRNAs regulate PCAF expression in PCa cells to regulate AR transcriptional activity is still unclear. Expression of PCAF was investigated in several PCa cell lines by qRT-PCR, Western blot, and immunocytochemistry. The effects of PCAF expression on AR-regulated transcriptional activity and cell growth in PCa cells were determined by chromatin immunoprecipitation, reporter gene construct analysis, and MTS assay. Targeting of PCAF by miR-17-5p was evaluated using the luciferase reporter assay. PCAF was upregulated in several PCa cell lines. Upregulation of PCAF promoted AR transcriptional activation and cell growth in cultured PCa cells. Expression of PCAF in PCa cells was associated with the downregulation of miR-17-5p. Targeting of the 3’-untranslated region of PCAF mRNA by miR-17-5p caused translational suppression and RNA degradation, and, consequently, modulation of AR transcriptional activity in PCa cells. PCAF is upregulated in cultured PCa cells, and upregulation of PCAF is associated with the downregulation of miR-17-5p. Targeting of PCAF by miR-17-5p modulates AR transcriptional activity and cell growth in cultured PCa cells

  6. The biological knowledge discovery by PCCF measure and PCA-F projection.

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    Jia, Xingang; Zhu, Guanqun; Han, Qiuhong; Lu, Zuhong

    2017-01-01

    In the process of biological knowledge discovery, PCA is commonly used to complement the clustering analysis, but PCA typically gives the poor visualizations for most gene expression data sets. Here, we propose a PCCF measure, and use PCA-F to display clusters of PCCF, where PCCF and PCA-F are modeled from the modified cumulative probabilities of genes. From the analysis of simulated and experimental data sets, we demonstrate that PCCF is more appropriate and reliable for analyzing gene expression data compared to other commonly used distances or similarity measures, and PCA-F is a good visualization technique for identifying clusters of PCCF, where we aim at such data sets that the expression values of genes are collected at different time points.

  7. Cyclin E/Cdk2, P/CAF, and E1A regulate the transactivation of the c-myc promoter by FOXM1

    International Nuclear Information System (INIS)

    Wierstra, Inken; Alves, Juergen

    2008-01-01

    FOXM1c transactivates the c-myc promoter by binding directly to its TATA-boxes. The present study demonstrates that the transactivation of the c-myc promoter by FOXM1c is enhanced by the key proliferation signal cyclin E/Cdk2, but repressed by P/CAF and the adenoviral oncoprotein E1A. Furthermore, FOXM1c interacts with the coactivator and histone acetyltransferase P/CAF. This study shows that, on the c-myc-P1 TATA-box, FOXM1c does not function simply as normal transcription factor just binding to an unusual site. Moreover, the inhibitory N-terminus of FOXM1c does not inhibit its transrepression domain or its EDA. Others reported that a cyclin/Cdk-binding LXL-motif of the splice variant FoxM1b is required for its interaction with Cdk2, Cdk1, and p27, its phosphorylation by Cdk1 and its activation by Cdc25B. In contrast, we now demonstrate that this LXL-motif is not required for the activation of FOXM1c by cyclin D1/Cdk4, cyclin E/Cdk and cyclin A/Cdk2 or for the repression of FOXM1c by p27

  8. Inhibition of PCAF Histone Acetyltransferase, Cytotoxicity and Cell Permeability of 2-Acylamino-1-(3- or 4-Carboxy-phenylbenzamides

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    Eunsook Ma

    2012-11-01

    Full Text Available Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenylbenzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B assay against seven human cancer cell lines: HT-29 (colon, HCT-116 (colon, MDA-231 (breast, A549 (lung, Hep3B (hepatoma, HeLa (cervical and Caki (kidney and one normal cell line (HSF. Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC50: 29.17 μM, human lung cancer (A549, IC50: 32.09 μM cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC50: 35.49 μM and HCT 116, IC50: 27.56 μM, human lung cancer (A549, IC50: 30.69 μM, and human cervical cancer (HeLa, IC50: 34.41 μM cell lines. The apparent permeability coefficient (Papp, cm/s values of two compounds (16 and 17 were evaluated as 68.21 and 71.48 × 10−6 cm/s by Caco-2 cell permeability assay.

  9. Inhibition of PCAF histone acetyltransferase, cytotoxicity and cell permeability of 2-acylamino-1-(3- or 4-carboxy-phenyl)benzamides.

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    Park, Woong Jae; Ma, Eunsook

    2012-11-05

    Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC(50): 29.17 μM), human lung cancer (A549, IC₅₀: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC₅₀: 35.49 μM and HCT 116, IC₅₀: 27.56 μM), human lung cancer (A549, IC₅₀: 30.69 μM), and human cervical cancer (HeLa, IC₅₀: 34.41 μM) cell lines. The apparent permeability coefficient (P(app), cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10⁻⁶ cm/s by Caco-2 cell permeability assay.

  10. Hepatitis C virus core protein regulates p300/CBP co-activation function. Possible role in the regulation of NF-AT1 transcriptional activity

    International Nuclear Information System (INIS)

    Gomez-Gonzalo, Marta; Benedicto, Ignacio; Carretero, Marta; Lara-Pezzi, Enrique; Maldonado-Rodriguez, Alejandra; Moreno-Otero, Ricardo; Lai, Michael M.C.; Lopez-Cabrera, Manuel

    2004-01-01

    Hepatitis C virus (HCV) core is a viral structural protein; it also participates in some cellular processes, including transcriptional regulation. However, the mechanisms of core-mediated transcriptional regulation remain poorly understood. Oncogenic virus proteins often target p300/CBP, a known co-activator of a wide variety of transcription factors, to regulate the expression of cellular and viral genes. Here we demonstrate, for the first time, that HCV core protein interacts with p300/CBP and enhances both its acetyl-transferase and transcriptional activities. In addition, we demonstrate that nuclear core protein activates the NH 2 -terminal transcription activation domain (TAD) of NF-AT1 in a p300/CBP-dependent manner. We propose a model in which core protein regulates the co-activation function of p300/CBP and activates NF-AT1, and probably other p300/CBP-regulated transcription factors, by a novel mechanism involving the regulation of the acetylation state of histones and/or components of the transcriptional machinery

  11. Insulin signaling regulates fatty acid catabolism at the level of CoA activation.

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    Xiaojun Xu

    2012-01-01

    Full Text Available The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS. We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

  12. The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos.

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    Crona, Filip; Holmqvist, Per-Henrik; Tang, Min; Singla, Bhumica; Vakifahmetoglu-Norberg, Helin; Fantur, Katrin; Mannervik, Mattias

    2015-11-01

    The Brakeless protein performs many important functions during Drosophila development, but how it controls gene expression is poorly understood. We previously showed that Brakeless can function as a transcriptional co-repressor. In this work, we perform transcriptional profiling of brakeless mutant embryos. Unexpectedly, the majority of affected genes are down-regulated in brakeless mutants. We demonstrate that genomic regions in close proximity to some of these genes are occupied by Brakeless, that over-expression of Brakeless causes a reciprocal effect on expression of these genes, and that Brakeless remains an activator of the genes upon fusion to an activation domain. Together, our results show that Brakeless can both repress and activate gene expression. A yeast two-hybrid screen identified the Mediator complex subunit Med19 as interacting with an evolutionarily conserved part of Brakeless. Both down- and up-regulated Brakeless target genes are also affected in Med19-depleted embryos, but only down-regulated targets are influenced in embryos depleted of both Brakeless and Med19. Our data provide support for a Brakeless activator function that regulates transcription by interacting with Med19. We conclude that the transcriptional co-regulator Brakeless can either activate or repress transcription depending on context. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Genetic variation in PCAF, a key mediator in epigenetics, is associated with reduced vascular morbidity and mortality: evidence for a new concept from three independent prospective studies

    NARCIS (Netherlands)

    Pons, D.; Trompet, S.; Craen, A.J.M.; Thijssen, P.E.; Quax, P.H.A.; de Vries, M.R.; Wierda, R.J.; van den Elsen, P.J.; Monraats, P.S.; Ewing, M.M.; Heijmans, B.T.; Slagboom, P.E.; Zwinderman, A.H.; Doevendans, P.A.F.M.; Tio, R.A.; de Winter, R.J.; de Maat, M.P.M.; Lakoubova, O.A.; Sattar, N.; Sheperd, J.; Westendorp, R.G.J.; Jukema, J.W.

    2011-01-01

    Aims: This study was designed to investigate the counterbalancing influence of genetic variation in the promoter of the gene encoding P300/CBP associated factor (PCAF), a lysine acetyltransferase (KAT), on coronary heart disease (CHD) and mortality. Methods and results: The association of genetic

  14. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

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    Malik, Sohail; Roeder, Robert G

    2010-11-01

    The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

  15. Inhibition of p53 acetylation by INHAT subunit SET/TAF-Iβ represses p53 activity.

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    Kim, Ji-Young; Lee, Kyu-Sun; Seol, Jin-Ee; Yu, Kweon; Chakravarti, Debabrata; Seo, Sang-Beom

    2012-01-01

    The tumor suppressor p53 responds to a wide variety of cellular stress signals. Among potential regulatory pathways, post-translational modifications such as acetylation by CBP/p300 and PCAF have been suggested for modulation of p53 activity. However, exactly how p53 acetylation is modulated remains poorly understood. Here, we found that SET/TAF-Iβ inhibited p300- and PCAF-mediated p53 acetylation in an INHAT (inhibitor of histone acetyltransferase) domain-dependent manner. SET/TAF-Iβ interacted with p53 and repressed transcription of p53 target genes. Consequently, SET/TAF-Iβ blocked both p53-mediated cell cycle arrest and apoptosis in response to cellular stress. Using different apoptosis analyses, including FACS, TUNEL and BrdU incorporation assays, we also found that SET/TAF-Iβ induced cellular proliferation via inhibition of p53 acetylation. Furthermore, we observed that apoptotic Drosophila eye phenotype induced by either dp53 overexpression or UV irradiation was rescued by expression of dSet. Inhibition of dp53 acetylation by dSet was observed in both cases. Our findings provide new insights into the regulation of stress-induced p53 activation by HAT-inhibiting histone chaperone SET/TAF-Iβ.

  16. PSG gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins.

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    Soledad A Camolotto

    Full Text Available BACKGROUND: Lysine acetylation is an important post-translational modification that plays a central role in eukaryotic transcriptional activation by modifying chromatin and transcription-related factors. Human pregnancy-specific glycoproteins (PSG are the major secreted placental proteins expressed by the syncytiotrophoblast at the end of pregnancy and represent early markers of cytotrophoblast differentiation. Low PSG levels are associated with complicated pregnancies, thus highlighting the importance of studying the mechanisms that control their expression. Despite several transcription factors having been implicated as key regulators of PSG gene family expression; the role of protein acetylation has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Here, we explored the role of acetylation on PSG gene expression in the human placental-derived JEG-3 cell line. Pharmacological inhibition of histone deacetylases (HDACs up-regulated PSG protein and mRNA expression levels, and augmented the amount of acetylated histone H3 associated with PSG 5'regulatory regions. Moreover, PSG5 promoter activation mediated by Sp1 and KLF6, via the core promoter element motif (CPE, -147/-140, was markedly enhanced in the presence of the HDAC inhibitor trichostatin A (TSA. This effect correlated with an increase in Sp1 acetylation and KLF6 nuclear localization as revealed by immunoprecipitation and subcellular fractionation assays. The co-activators PCAF, p300, and CBP enhanced Sp1-dependent PSG5 promoter activation through their histone acetylase (HAT function. Instead, p300 and CBP acetyltransferase domain was dispensable for sustaining co-activation of PSG5 promoter by KLF6. CONCLUSIONS/SIGNIFICANCE: Results are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6 following an augmented Sp1 acetylation and KLF6 nuclear localization.

  17. A function-based screen for seeking RubisCO active clones from metagenomes: novel enzymes influencing RubisCO activity.

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    Böhnke, Stefanie; Perner, Mirjam

    2015-03-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) is a key enzyme of the Calvin cycle, which is responsible for most of Earth's primary production. Although research on RubisCO genes and enzymes in plants, cyanobacteria and bacteria has been ongoing for years, still little is understood about its regulation and activation in bacteria. Even more so, hardly any information exists about the function of metagenomic RubisCOs and the role of the enzymes encoded on the flanking DNA owing to the lack of available function-based screens for seeking active RubisCOs from the environment. Here we present the first solely activity-based approach for identifying RubisCO active fosmid clones from a metagenomic library. We constructed a metagenomic library from hydrothermal vent fluids and screened 1056 fosmid clones. Twelve clones exhibited RubisCO activity and the metagenomic fragments resembled genes from Thiomicrospira crunogena. One of these clones was further analyzed. It contained a 35.2 kb metagenomic insert carrying the RubisCO gene cluster and flanking DNA regions. Knockouts of twelve genes and two intergenic regions on this metagenomic fragment demonstrated that the RubisCO activity was significantly impaired and was attributed to deletions in genes encoding putative transcriptional regulators and those believed to be vital for RubisCO activation. Our new technique revealed a novel link between a poorly characterized gene and RubisCO activity. This screen opens the door to directly investigating RubisCO genes and respective enzymes from environmental samples.

  18. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

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    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  19. Regulation of gene expression by manipulating transcriptional repressor activity using a novel CoSRI technology.

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    Xu, Yue; Li, Song Feng; Parish, Roger W

    2017-07-01

    Targeted gene manipulation is a central strategy for studying gene function and identifying related biological processes. However, a methodology for manipulating the regulatory motifs of transcription factors is lacking as these factors commonly possess multiple motifs (e.g. repression and activation motifs) which collaborate with each other to regulate multiple biological processes. We describe a novel approach designated conserved sequence-guided repressor inhibition (CoSRI) that can specifically reduce or abolish the repressive activities of transcription factors in vivo. The technology was evaluated using the chimeric MYB80-EAR transcription factor and subsequently the endogenous WUS transcription factor. The technology was employed to develop a reversible male sterility system applicable to hybrid seed production. In order to determine the capacity of the technology to regulate the activity of endogenous transcription factors, the WUS repressor was chosen. The WUS repression motif could be inhibited in vivo and the transformed plants exhibited the wus-1 phenotype. Consequently, the technology can be used to manipulate the activities of transcriptional repressor motifs regulating beneficial traits in crop plants and other eukaryotic organisms. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  20. Proposing a Model of Co-Regulated Learning for Graduate Medical Education.

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    Rich, Jessica V

    2017-08-01

    Primarily grounded in Zimmerman's social cognitive model of self-regulation, graduate medical education is guided by principles that self-regulated learning takes place within social context and influence, and that the social context and physical environment reciprocally influence persons and their cognition, behavior, and development. However, contemporary perspectives on self-regulation are moving beyond Zimmerman's triadic reciprocal orientation to models that consider social transactions as the central core of regulated learning. Such co-regulated learning models emphasize shared control of learning and the role more advanced others play in scaffolding novices' metacognitive engagement.Models of co-regulated learning describe social transactions as periods of distributed regulation among individuals, which instrumentally promote or inhibit the capacity for individuals to independently self-regulate. Social transactions with other regulators, including attending physicians, more experienced residents, and allied health care professionals, are known to mediate residents' learning and to support or hamper the development of their self-regulated learning competence. Given that social transactions are at the heart of learning-oriented assessment and entrustment decisions, an appreciation for co-regulated learning is likely important for advancing medical education research and practice-especially given the momentum of new innovations such as entrustable professional activities.In this article, the author explains why graduate medical educators should consider adopting a model of co-regulated learning to complement and extend Zimmerman's models of self-regulated learning. In doing so, the author suggests a model of co-regulated learning and provides practical examples of how the model is relevant to graduate medical education research and practice.

  1. Acetylation Increases EWS-FLI1 DNA Binding and Transcriptional Activity

    International Nuclear Information System (INIS)

    Schlottmann, Silke; Erkizan, Hayriye V.; Barber-Rotenberg, Julie S.; Knights, Chad; Cheema, Amrita; Üren, Aykut; Avantaggiati, Maria L.; Toretsky, Jeffrey A.

    2012-01-01

    Ewing Sarcoma (ES) is associated with a balanced chromosomal translocation that in most cases leads to the expression of the oncogenic fusion protein and transcription factor EWS-FLI1. EWS-FLI1 has been shown to be crucial for ES cell survival and tumor growth. However, its regulation is still enigmatic. To date, no functionally significant post-translational modifications of EWS-FLI1 have been shown. Since ES are sensitive to histone deacetylase inhibitors (HDI), and these inhibitors are advancing in clinical trials, we sought to identify if EWS-FLI1 is directly acetylated. We convincingly show acetylation of the C-terminal FLI1 (FLI1-CTD) domain, which is the DNA binding domain of EWS-FLI1. In vitro acetylation studies showed that acetylated FLI1-CTD has higher DNA binding activity than the non-acetylated protein. Over-expression of PCAF or treatment with HDI increased the transcriptional activity of EWS-FLI1, when co-expressed in Cos7 cells. However, our data that evaluates the acetylation of full-length EWS-FLI1 in ES cells remains unclear, despite creating acetylation specific antibodies to four potential acetylation sites. We conclude that EWS-FLI1 may either gain access to chromatin as a result of histone acetylation or undergo regulation by direct acetylation. These data should be considered when patients are treated with HDAC inhibitors. Further investigation of this phenomenon will reveal if this potential acetylation has an impact on tumor response.

  2. Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

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    Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

    2015-01-01

    Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

  3. Co-ordinate regulation of sterol biosynthesis enzyme activity during accumulation of sterols in developing rape and tobacco seed.

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    Harker, Mark; Hellyer, Amanda; Clayton, John C; Duvoix, Annelyse; Lanot, Alexandra; Safford, Richard

    2003-02-01

    The activities of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, sterol methyl transferase 1 and sterol acyltransferase, key enzymes involved in phytosterol biosynthesis were shown to be co-ordinately regulated during oilseed rape ( Brassica napus L.) and tobacco ( Nicotiana tabacum L.) seed development. In both plants, enzyme activities were low during the initial stages of seed development, increasing towards mid-maturation where they remained stable for a time, before declining rapidly as the oilseeds reached maturity. During seed development, the level of total sterols increased 12-fold in tobacco and 9-fold in rape, primarily due to an increase in steryl ester production. In both seed tissues, stages of maximum enzyme activity coincided with periods of high rates of sterol production, indicating developmental regulation of the enzymes to be responsible for the increases in the sterol content observed during seed development. Consistent with previous studies the data presented suggest that sterol biosynthesis is regulated by two key steps, although there may be others. The first is the regulation of carbon flux into the isoprenoid pathway to cycloartenol. The second is the flux from cycloartenol to Delta(5)-end-product sterols. The implications of the results in terms of enhancing seed sterol levels by genetic modification are also discussed.

  4. Stearoyl-CoA desaturase – the lipid metabolism regulator

    Directory of Open Access Journals (Sweden)

    Mirosław Kucharski

    2014-03-01

    Full Text Available Stearoyl-CoA desaturase is an enzyme from the class of oxidoreductase, which catalyzes the formation of a fatty acid double bond between C9 and C10. It plays a key role in composition of the fatty acid profile in adipose tissue and animal products such as meat and milk. Additionally, it is an important regulator of metabolic processes in the body, and it determines the maintenance of energy homeostasis. This enzyme is encoded by an SCD gene, which, depending on the species, may exist as different isoforms. mRNA expression of stearoyl-CoA desaturase is dependent on many factors, including diet, hormones, and the activity of other genes. In previous studies, several mutations were characterized within the sequence of Δ9-desaturase, which may affect the activity of the protein in the tissues, as well as the value of breeding animals. Effects of particular mutations of the gene encoding the enzyme appears to be particularly important for diseases associated with obesity, diabetes, hypertension, heart diseases or cancer in humans. Also, it seems that using sheep as a potential animal model could be helpful in uncovering and understanding the mechanisms regulated by stearoyl-CoA desaturase.

  5. Acetyl-CoA carboxylase in Reuber hepatoma cells: variation in enzyme activity, insulin regulation, and cellular lipid content.

    Science.gov (United States)

    Bianchi, A; Evans, J L; Nordlund, A C; Watts, T D; Witters, L A

    1992-01-01

    Reuber hepatoma cells are useful cultured lines for the study of insulin action, lipid and lipoprotein metabolism, and the regulation of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis. During investigations in different clonal lines of these cells, we have uncovered marked intercellular variability in the activity, enzyme content, and insulin regulation of ACC paralleled by differences in cellular neutral lipid (triglyceride) content. Two contrasting clonal lines, Fao and H356A-1, have been studied in detail. Several features distinguish these two lines, including differences in ACC activity and enzyme kinetics, the content of the two major hepatic ACC isozymes (Mr 280,000 and 265,000 Da) and their heteroisozymic complex, the extent of ACC phosphorylation, and the ability of ACC to be activated on stimulation by insulin and insulinomimetic agonists. As studied by Nile Red staining and fluorescence-activated cell sorting, these two lines also display marked differences in neutral lipid content, which correlates with both basal levels of ACC activity and inhibition of ACC by the fatty acid analog, 5-(tetradecyloxy)-2-furoic acid (TOFA). These results emphasize the importance of characterization of any particular clonal line of Reuber cells for studies of enzyme regulation, substrate metabolism, and hormone action. With respect to ACC, studies in contrasting clonal lines of Reuber cells could provide valuable clues to understanding both the complex mechanisms of intracellular ACC regulation in the absence and presence of hormones and its regulatory role(s) in overall hepatic lipid metabolism.

  6. Intracellular long-chain acyl CoAs activate TRPV1 channels.

    Directory of Open Access Journals (Sweden)

    Yi Yu

    Full Text Available TRPV1 channels are an important class of membrane proteins that play an integral role in the regulation of intracellular cations such as calcium in many different tissue types. The anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2 is a known positive modulator of TRPV1 channels and the negatively charged phosphate groups interact with several basic amino acid residues in the proximal C-terminal TRP domain of the TRPV1 channel. We and other groups have shown that physiological sub-micromolar levels of long-chain acyl CoAs (LC-CoAs, another ubiquitous anionic lipid, can also act as positive modulators of ion channels and exchangers. Therefore, we investigated whether TRPV1 channel activity is similarly regulated by LC-CoAs. Our results show that LC-CoAs are potent activators of the TRPV1 channel and interact with the same PIP2-binding residues in TRPV1. In contrast to PIP2, LC-CoA modulation of TRPV1 is independent of Ca2+i, acting in an acyl side-chain saturation and chain-length dependent manner. Elevation of LC-CoAs in intact Jurkat T-cells leads to significant increases in agonist-induced Ca2+i levels. Our novel findings indicate that LC-CoAs represent a new fundamental mechanism for regulation of TRPV1 channel activity that may play a role in diverse cell types under physiological and pathophysiological conditions that alter fatty acid transport and metabolism such as obesity and diabetes.

  7. CO2 sensing and CO2 regulation of stomatal conductance: advances and open questions

    Science.gov (United States)

    Engineer, Cawas; Hashimoto-Sugimoto, Mimi; Negi, Juntaro; Israelsson-Nordstrom, Maria; Azoulay-Shemer, Tamar; Rappel, Wouter-Jan; Iba, Koh; Schroeder, Julian

    2015-01-01

    Guard cells form epidermal stomatal gas exchange valves in plants and regulate the aperture of stomatal pores in response to changes in the carbon dioxide (CO2) concentration in leaves. Moreover, the development of stomata is repressed by elevated CO2 in diverse plant species. Evidence suggests that plants can sense CO2 concentration changes via guard cells and via mesophyll tissues in mediating stomatal movements. We review new discoveries and open questions on mechanisms mediating CO2-regulated stomatal movements and CO2 modulation of stomatal development, which together function in CO2-regulation of stomatal conductance and gas exchange in plants. Research in this area is timely in light of the necessity of selecting and developing crop cultivars which perform better in a shifting climate. PMID:26482956

  8. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

    Science.gov (United States)

    Montgomery, David C; Sorum, Alexander W; Guasch, Laura; Nicklaus, Marc C; Meier, Jordan L

    2015-08-20

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the metabolic regulation of lysine acetyltransferase (KAT) enzymes. Using a novel chemoproteomic probe, we identify a previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes. Further analysis reveals that palmitoyl-CoA is a potent inhibitor of KAT activity and that fatty acyl-CoA precursors reduce cellular histone acetylation levels. These studies implicate fatty acyl-CoAs as endogenous regulators of histone acetylation, and suggest novel strategies for the investigation and metabolic modulation of epigenetic signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

    Directory of Open Access Journals (Sweden)

    Júlia T. Novaes

    2017-10-01

    Full Text Available Tetrahydrocurcumin (THC, curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa. Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC activity, histone acetyltransferase (HAT activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

  10. Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma

    Directory of Open Access Journals (Sweden)

    Berthold Frank

    2009-04-01

    Full Text Available Abstract Background HAND2, a key regulator for the development of the sympathetic nervous system, is located on chromosome 4q33 in a head-to-head orientation with DEIN, a recently identified novel gene with stage specific expression in primary neuroblastoma (NB. Both genes are expressed in primary NB as well as most NB cell lines and are separated by a genomic sequence of 228 bp. The similar expression profile of both genes suggests a common transcriptional regulation mediated by a bidirectional promoter. Results Northern Blot analysis of DEIN and HAND2 in 20 primary NBs indicated concurrent expression levels of the two genes, which was confirmed by microarray analysis of 236 primary NBs (Pearson's correlation coefficient r = 0.65. While DEIN expression in the latter cohort was associated with stage 4S (p = 0.02, HAND2 expression was not associated with tumor stage. In contrast, both HAND2 and DEIN transcript levels were highly associated with age at diagnosis DEIN orientation, an average 3.4 fold increase in activity was observed as compared to the promoterless vector, whereas an average 15.4 fold activation was detected in HAND2 orientation. The presence of two highly conserved putative regulatory elements, one of which was shown to enhance HAND2 expression in branchial arches previously, displayed weak repressor activity for both genes. Conclusion HAND2 and DEIN represent a gene pair that is tightly linked by a bidirectional promoter in an evolutionary highly conserved manner. Expression of both genes in NB is co-regulated by asymmetrical activity of this promoter and modulated by the activity of two cis-regulatory elements acting as weak repressors. The concurrent quantitative and tissue specific expression of HAND2 and DEIN suggests a functional link between both genes.

  11. TBLR1 regulates the expression of nuclear hormone receptor co-repressors

    Directory of Open Access Journals (Sweden)

    Brown Stuart

    2006-08-01

    Full Text Available Abstract Background Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. Results TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of

  12. Regulation of pH in human skeletal muscle: adaptations to physical activity

    DEFF Research Database (Denmark)

    Juel, C

    2008-01-01

    -transport) and describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....... resonance technique to exercise experiments including blood sampling and muscle biopsies. The present review characterizes the cellular buffering system as well as the most important membrane transport systems involved (Na(+)/H(+) exchange, Na-bicarbonate co-transport and lactate/H(+) co...

  13. Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.

    Science.gov (United States)

    Khandokar, Yogesh B; Srivastava, Parul; Cowieson, Nathan; Sarker, Subir; Aragao, David; Das, Shubagata; Smith, Kate M; Raidal, Shane R; Forwood, Jade K

    2017-12-15

    Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. Although many of these enzyme families are well-characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis Structural analysis with X-ray crystallographic diffraction data to 2.0-Å revealed that each protein subunit harbors a hot dog-fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed the greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn 24 and Asp 39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg 93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9.

    Science.gov (United States)

    Pohlers, Susann; Martin, Ronny; Krüger, Thomas; Hellwig, Daniela; Hänel, Frank; Kniemeyer, Olaf; Saluz, Hans Peter; Van Dijck, Patrick; Ernst, Joachim F; Brakhage, Axel; Mühlschlegel, Fritz A; Kurzai, Oliver

    2017-01-31

    Adaptation to alternating CO 2 concentrations is crucial for all organisms. Carbonic anhydrases-metalloenzymes that have been found in all domains of life-enable fixation of scarce CO 2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO 2 ). Expression of NCE103 is regulated in response to CO 2 availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, and in Candida albicans and Candida glabrata, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO 2 -dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the sch9Δ mutant strain showed deregulated NCE103 expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO 2 -dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata Deletion of SCH9 homologues of both species impaired CO 2 -dependent regulation of NCE103 expression, which indicates a conservation of the CO 2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO 2 adaptation to lipid signaling via Pkh1/2 in fungi. All living organisms have to cope with alternating CO 2 concentrations as CO 2 levels range from very low in the atmosphere (0.04%) to high (5% and more) in other niches, including the human body. In fungi, CO 2 is sensed via two pathways. The first regulates virulence in

  15. Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9

    Directory of Open Access Journals (Sweden)

    Susann Pohlers

    2017-01-01

    Full Text Available Adaptation to alternating CO2 concentrations is crucial for all organisms. Carbonic anhydrases—metalloenzymes that have been found in all domains of life—enable fixation of scarce CO2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO2. Expression of NCE103 is regulated in response to CO2 availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, and in Candida albicans and Candida glabrata, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO2-dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the sch9Δ mutant strain showed deregulated NCE103 expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO2-dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata. Deletion of SCH9 homologues of both species impaired CO2-dependent regulation of NCE103 expression, which indicates a conservation of the CO2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO2 adaptation to lipid signaling via Pkh1/2 in fungi.

  16. Reconstitution of CO2 Regulation of SLAC1 Anion Channel and Function of CO2-Permeable PIP2;1 Aquaporin as CARBONIC ANHYDRASE4 Interactor

    Science.gov (United States)

    Zeise, Brian; Xu, Danyun; Rappel, Wouter-Jan; Boron, Walter F.; Schroeder, Julian I.

    2016-01-01

    Dark respiration causes an increase in leaf CO2 concentration (Ci), and the continuing increases in atmospheric [CO2] further increases Ci. Elevated leaf CO2 concentration causes stomatal pores to close. Here, we demonstrate that high intracellular CO2/HCO3− enhances currents mediated by the Arabidopsis thaliana guard cell S-type anion channel SLAC1 upon coexpression of any one of the Arabidopsis protein kinases OST1, CPK6, or CPK23 in Xenopus laevis oocytes. Split-ubiquitin screening identified the PIP2;1 aquaporin as an interactor of the βCA4 carbonic anhydrase, which was confirmed in split luciferase, bimolecular fluorescence complementation, and coimmunoprecipitation experiments. PIP2;1 exhibited CO2 permeability. Mutation of PIP2;1 in planta alone was insufficient to impair CO2- and abscisic acid-induced stomatal closing, likely due to redundancy. Interestingly, coexpression of βCA4 and PIP2;1 with OST1-SLAC1 or CPK6/23-SLAC1 in oocytes enabled extracellular CO2 enhancement of SLAC1 anion channel activity. An inactive PIP2;1 point mutation was identified that abrogated water and CO2 permeability and extracellular CO2 regulation of SLAC1 activity. These findings identify the CO2-permeable PIP2;1 as key interactor of βCA4 and demonstrate functional reconstitution of extracellular CO2 signaling to ion channel regulation upon coexpression of PIP2;1, βCA4, SLAC1, and protein kinases. These data further implicate SLAC1 as a bicarbonate-responsive protein contributing to CO2 regulation of S-type anion channels. PMID:26764375

  17. Semipermeable Capsules Wrapping a Multifunctional and Self-regulated Co-culture Microenvironment for Osteogenic Differentiation

    Science.gov (United States)

    Correia, Clara R.; Pirraco, Rogério P.; Cerqueira, Mariana T.; Marques, Alexandra P.; Reis, Rui L.; Mano, João F.

    2016-02-01

    A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the “stem cell niche”, the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources.

  18. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

    Directory of Open Access Journals (Sweden)

    Allan Andrew C

    2008-07-01

    , it does provide a tool to characterise cis-regulatory sequences that are necessary for transcription activation in a complex list of co-ordinately regulated genes.

  19. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    International Nuclear Information System (INIS)

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik

    2014-01-01

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

  20. Correlation set analysis: detecting active regulators in disease populations using prior causal knowledge

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    Huang Chia-Ling

    2012-03-01

    Full Text Available Abstract Background Identification of active causal regulators is a crucial problem in understanding mechanism of diseases or finding drug targets. Methods that infer causal regulators directly from primary data have been proposed and successfully validated in some cases. These methods necessarily require very large sample sizes or a mix of different data types. Recent studies have shown that prior biological knowledge can successfully boost a method's ability to find regulators. Results We present a simple data-driven method, Correlation Set Analysis (CSA, for comprehensively detecting active regulators in disease populations by integrating co-expression analysis and a specific type of literature-derived causal relationships. Instead of investigating the co-expression level between regulators and their regulatees, we focus on coherence of regulatees of a regulator. Using simulated datasets we show that our method performs very well at recovering even weak regulatory relationships with a low false discovery rate. Using three separate real biological datasets we were able to recover well known and as yet undescribed, active regulators for each disease population. The results are represented as a rank-ordered list of regulators, and reveals both single and higher-order regulatory relationships. Conclusions CSA is an intuitive data-driven way of selecting directed perturbation experiments that are relevant to a disease population of interest and represent a starting point for further investigation. Our findings demonstrate that combining co-expression analysis on regulatee sets with a literature-derived network can successfully identify causal regulators and help develop possible hypothesis to explain disease progression.

  1. Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes

    DEFF Research Database (Denmark)

    Hu, Liping; Deeney, Jude T; Nolan, Christopher J

    2005-01-01

    -cells. The mechanisms by which lipolysis is regulated in different tissues is, therefore, of considerable interest. Here, the effects of long-chain acyl-CoA esters (LC-CoA) on lipase activity in islets and adipocytes were compared. Palmitoyl-CoA (Pal-CoA, 1-10 microM) stimulated lipase activity in islets from both....... The inhibitory effect of LC-CoA on adipocyte HSL was dependent on phosphorylation and enhanced by acyl-CoA-binding protein (ACBP). In contrast, the stimulatory effect on islet lipase activity was blocked by ACBP, presumably due to binding and sequestration of LC-CoA. These data suggest the following intertissue...

  2. Culture as Mediator: Co-Regulation, Self-Regulation, and Middle School Mathematics Achievement

    Science.gov (United States)

    Hinnant-Crawford, Brandi Nicole; Faison, Morgan Z.; Chang, Mei-Lin

    2016-01-01

    Purpose: Self-regulation is defined as strategic, metacognitive behavior, motivation and cognition aimed at a goal (Zimmmerman and Schunk, 2011). Co-regulation, arguably more aligned with norms in communal cultures, is the process of learners sharing "a common problem-solving plane" through which self-regulatory strategies are learned…

  3. Regulating forest rotation to increase CO{sub 2} sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Gong, P.; Kristroem, B.

    1999-06-01

    Previous studies have shown that the optimal forest rotation age increases considerably if the benefits of CO{sub 2} sequestration are included in rotation decisions. While these studies provide some guidelines for managing public forests, private forest owners may not choose the socially optimal rotation age. This paper discusses a regulation measure to increase CO{sub 2} sequestration in privately owned forests. The regulation problem is treated as a sequential game, where the regulator chooses a subsidy scheme and forest owners respond by changing rotation ages. A private forest owner receives a subsidy at the time of harvesting if he/she changes the rotation age towards the socially optimal one. The subsidy is proportional to the associated change in timber yield. The forest owner`s objective is to maximize the net present value of after-tax timber production profits and subsidies. The regulator`s decision problem is to find the subsidy rate that maximizes the net benefits of implementing the policy (the net of increased CO{sub 2} sequestration benefits, subsidy costs, and changes in forestry taxation income). Empirical results for Swedish examples show that the optimal subsidy rate is sensitive to the marginal benefit of CO{sub 2} sequestration, the social discount rate, and site quality. The optimal subsidy rate is found to be significantly lower than the marginal benefit of CO{sub 2} sequestration. With the proposed subsidy scheme, private forest owners will choose rotation ages longer than the Faustmann rotation, but significantly shorter than the socially optimal rotation age 21 refs, 6 tabs. Arbetsrapport 272

  4. Regulated deficit irrigation can decrease soil CO2 emissions in fruit orchards

    Science.gov (United States)

    Zornoza, Raul; Acosta, José Alberto; Martínez-Martínez, Silvia; De la Rosa, Jose M.°; Faz, Angel; Pérez-Pastor, Alejandro

    2016-04-01

    Irrigation water restrictions in the Mediterranean area have created a growing interest in water conservation. Apart from environmental and economic benefits by water savings, regulated deficit irrigation (RDI) may contribute to reduce soil CO2 emissions and enhance C sequestration in soils, by decreasing microbial and root activity in response to decreased soil moisture levels. An experiment was established in four orchards (peach, apricot, Saturn peach and grape) to investigate the effects of regulated deficit irrigation (RDI) on soil CO2 emissions. Two irrigation treatments were assayed: full irrigation (FI), and RDI, irrigated as FI except for postharvest period (peach, apricot, Saturn peach) or post-veraison period (grape) were 50% of FI was applied. The application of deficit caused a significant decrease in CO2 emission rates, with rates in average of 90 mg CO2-C m-2 h-1, 120 mg CO2-C m-2 h-1, 60 mg CO2-C m-2 h-1 and 60 mg CO2-C m-2 h-1 lower than FI during the period when deficit was applied for peach, apricot, Saturn peach and grape. This confirms the high effectiveness of the RDI strategies not only to save water consumption but also to decrease soil CO2 emissions. However, monitoring during longer periods is needed to verify that this trend is long-term maintained, and assess if soil carbon stocks are increase or most CO2 emissions derive from root respiration. Acknowledgements This work has been funded by the European Union LIFE+ project IRRIMAN (LIFE13 ENV/ES/000539).

  5. Malonyl-CoA decarboxylase (MCD) is differentially regulated in subcellular compartments by 5'AMP-activated protein kinase (AMPK). Studies using H9c2 cells overexpressing MCD and AMPK by adenoviral gene transfer technique.

    Science.gov (United States)

    Sambandam, Nandakumar; Steinmetz, Michael; Chu, Angel; Altarejos, Judith Y; Dyck, Jason R B; Lopaschuk, Gary D

    2004-07-01

    Malonyl-CoA, a potent inhibitor of carnitine pamitoyl transferase-I (CPT-I), plays a pivotal role in fuel selection in cardiac muscle. Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, removes a potent allosteric inhibition on CPT-I and thereby increases fatty acid oxidation in the heart. Although MCD has several Ser/Thr phosphorylation sites, whether it is regulated by AMP-activated protein kinase (AMPK) has been controversial. We therefore overexpressed MCD (Ad.MCD) and constitutively active AMPK (Ad.CA-AMPK) in H9c2 cells, using an adenoviral gene delivery approach in order to examine if MCD is regulated by AMPK. Cells infected with Ad.CA-AMPK demonstrated a fourfold increase in AMPK activity as compared with control cells expressing green fluorescent protein (Ad.GFP). MCD activity increased 40- to 50-fold in Ad.MCD + Ad.GFP cells when compared with Ad.GFP control. Co-expressing AMPK with MCD further augmented MCD expression and activity in Ad.MCD + Ad.CA-AMPK cells compared with the Ad.MCD + Ad.GFP control. Subcellular fractionation further revealed that 54.7 kDa isoform of MCD expression was significantly higher in cytosolic fractions of Ad.MCD + Ad.CA-AMPK cells than of the Ad.MCD +Ad.GFP control. However, the MCD activities in cytosolic fractions were not different between the two groups. Interestingly, in the mitochondrial fractions, MCD activity significantly increased in Ad.MCD + Ad.CA-AMPK cells when compared with Ad.MCD + Ad.GFP cells. Using phosphoserine and phosphothreonine antibodies, no phosphorylation of MCD by AMPK was observed. The increase in MCD activity in mitochondria-rich fractions of Ad.MCD + Ad.CA-AMPK cells was accompanied by an increase in the level of the 50.7 kDa isoform of MCD protein in the mitochondria. This differential regulation of MCD expression and activity in the mitochondria by AMPK may potentially regulate malonyl-CoA levels at sites nearby CPT-I on the mitochondria.

  6. A unified molecular mechanism for the regulation of acetyl-CoA carboxylase by phosphorylation.

    Science.gov (United States)

    Wei, Jia; Zhang, Yixiao; Yu, Tai-Yuan; Sadre-Bazzaz, Kianoush; Rudolph, Michael J; Amodeo, Gabriele A; Symington, Lorraine S; Walz, Thomas; Tong, Liang

    2016-01-01

    Acetyl-CoA carboxylases (ACCs) are crucial metabolic enzymes and attractive targets for drug discovery. Eukaryotic acetyl-CoA carboxylases are 250 kDa single-chain, multi-domain enzymes and function as dimers and higher oligomers. Their catalytic activity is tightly regulated by phosphorylation and other means. Here we show that yeast ACC is directly phosphorylated by the protein kinase SNF1 at residue Ser1157, which potently inhibits the enzyme. Crystal structure of three ACC central domains (AC3-AC5) shows that the phosphorylated Ser1157 is recognized by Arg1173, Arg1260, Tyr1113 and Ser1159. The R1173A/R1260A double mutant is insensitive to SNF1, confirming that this binding site is crucial for regulation. Electron microscopic studies reveal dramatic conformational changes in the holoenzyme upon phosphorylation, likely owing to the dissociation of the biotin carboxylase domain dimer. The observations support a unified molecular mechanism for the regulation of ACC by phosphorylation as well as by the natural product soraphen A, a potent inhibitor of eukaryotic ACC. These molecular insights enhance our understanding of acetyl-CoA carboxylase regulation and provide a basis for drug discovery.

  7. pCO2 And pH regulation of cerebral blood flow

    Directory of Open Access Journals (Sweden)

    SeongHun eYoon

    2012-09-01

    Full Text Available CO2 Serves as one of the fundamental regulators of cerebral blood flow. It is widely considered that this regulation occurs through pCO2-driven changes in pH of the cerebral spinal fluid, with elevated and lowered pH causing direct relaxation and contraction of the smooth muscle, respectively. However, some findings also suggest that pCO2 acts independently of and/or in conjunction with altered pH. This action may be due to a direct effect of cerebral spinal fluid pCO2 on the smooth muscle as well as on the endothelium, nerves, and astrocytes. Findings may also point to an action of arterial pCO2 on the endothelium to regulate smooth muscle contractility. Thus, the effects of pH and pCO2 may be influenced by the absence/presence of different cell types in the various experimental preparations. Results may also be influenced by experimental parameters including myogenic tone as well as solutions containing significantly altered HCO3- concentrations, i.e., solutions routinely employed to differentiate the effects of pH from pCO2. In sum, it appears that pCO2, independently and in conjunction with pH, may regulate cerebral blood flow.

  8. A toll-like receptor 2 pathway regulates the Ppargc1a/b metabolic co-activators in mice with Staphylococcal aureus sepsis.

    Directory of Open Access Journals (Sweden)

    Timothy E Sweeney

    Full Text Available Activation of the host antibacterial defenses by the toll-like receptors (TLR also selectively activates energy-sensing and metabolic pathways, but the mechanisms are poorly understood. This includes the metabolic and mitochondrial biogenesis master co-activators, Ppargc1a (PGC-1α and Ppargc1b (PGC-1β in Staphylococcus aureus (S. aureus sepsis. The expression of these genes in the liver is markedly attenuated inTLR2(-/- mice and markedly accentuated in TLR4(-/- mice compared with wild type (WT mice. We sought to explain this difference by using specific TLR-pathway knockout mice to test the hypothesis that these co-activator genes are directly regulated through TLR2 signaling. By comparing their responses to S. aureus with WT mice, we found that MyD88-deficient and MAL-deficient mice expressed hepatic Ppargc1a and Ppargc1b normally, but that neither gene was activated in TRAM-deficient mice. Ppargc1a/b activation did not require NF-kβ, but did require an interferon response factor (IRF, because neither gene was activated in IRF-3/7 double-knockout mice in sepsis, but both were activated normally in Unc93b1-deficient (3d mice. Nuclear IRF-7 levels in TLR2(-/- and TLR4(-/- mice decreased and increased respectively post-inoculation and IRF-7 DNA-binding at the Ppargc1a promoter was demonstrated by chromatin immunoprecipitation. Also, a TLR2-TLR4-TRAM native hepatic protein complex was detected by immunoprecipitation within 6 h of S. aureus inoculation that could support MyD88-independent signaling to Ppargc1a/b. Overall, these findings disclose a novel MyD88-independent pathway in S. aureus sepsis that links TLR2 and TLR4 signaling in innate immunity to Ppargc1a/b gene regulation in a critical metabolic organ, the liver, by means of TRAM, TRIF, and IRF-7.

  9. Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT.

    Science.gov (United States)

    van Leeuwen, Hans; Okuwaki, Mitsuru; Hong, Rui; Chakravarti, Debabrata; Nagata, Kyosuke; O'Hare, Peter

    2003-09-01

    Affinity chromatography was used to identify cellular proteins that interact with the herpes simplex virus (HSV) tegument protein VP22. Among a small set of proteins that bind specifically to VP22, we identified TAF-I (template-activating factor I), a chromatin remodelling protein and close homologue of the histone chaperone protein NAP-1. TAF-I has been shown previously to promote more ordered transfer of histones to naked DNA through a direct interaction with histones. TAF-I, as a subunit of the INHAT (inhibitor of acetyltransferases) protein complex, also binds to histones and masks them from being substrates for the acetyltransferases p300 and PCAF. Using in vitro assays for TAF-I activity in chromatin assembly, we show that VP22 inhibits nucleosome deposition on DNA by binding to TAF-I. We also observed that VP22 binds non-specifically to DNA, an activity that is abolished by TAF-I. However, the presence of VP22 does not affect the property of INHAT in inhibiting the histone acetyltransferase activity of p300 or PCAF in vitro. We speculate that this interaction could be relevant to HSV DNA organization early in infection, for example, by interfering with nucleosomal deposition on the genome. Consistent with this possibility was the observation that overexpression of TAF-I in transfected cells interferes with the progression of HSV-1 infection.

  10. SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain acyl-CoA dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Yuxun Zhang

    Full Text Available SIRT3 and SIRT5 have been shown to regulate mitochondrial fatty acid oxidation but the molecular mechanisms behind the regulation are lacking. Here, we demonstrate that SIRT3 and SIRT5 both target human very long-chain acyl-CoA dehydrogenase (VLCAD, a key fatty acid oxidation enzyme. SIRT3 deacetylates and SIRT5 desuccinylates K299 which serves to stabilize the essential FAD cofactor in the active site. Further, we show that VLCAD binds strongly to cardiolipin and isolated mitochondrial membranes via a domain near the C-terminus containing lysines K482, K492, and K507. Acetylation or succinylation of these residues eliminates binding of VLCAD to cardiolipin. SIRT3 deacetylates K507 while SIRT5 desuccinylates K482, K492, and K507. Sirtuin deacylation of recombinant VLCAD rescues membrane binding. Endogenous VLCAD from SIRT3 and SIRT5 knockout mouse liver shows reduced binding to cardiolipin. Thus, SIRT3 and SIRT5 promote fatty acid oxidation by converging upon VLCAD to promote its activity and membrane localization. Regulation of cardiolipin binding by reversible lysine acylation is a novel mechanism that is predicted to extrapolate to other metabolic proteins that localize to the inner mitochondrial membrane.

  11. Co-Transcriptional Folding and Regulation Mechanisms of Riboswitches

    Directory of Open Access Journals (Sweden)

    Sha Gong

    2017-07-01

    Full Text Available Riboswitches are genetic control elements within non-coding regions of mRNA. These self-regulatory elements have been found to sense a range of small metabolites, ions, and other physical signals to exert regulatory control of transcription, translation, and splicing. To date, more than a dozen riboswitch classes have been characterized that vary widely in size and secondary structure. Extensive experiments and theoretical studies have made great strides in understanding the general structures, genetic mechanisms, and regulatory activities of individual riboswitches. As the ligand-dependent co-transcriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolites under the transcription. This review will provide a brief summary of the studies about the regulation mechanisms of the pbuE, SMK, yitJ, and metF riboswitches based on the ligand-dependent co-transcriptional folding of the riboswitches.

  12. CO{sub 2} regulation. The case of Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Tinggaard Svendsen, G. [Faculty of Business Administration, Dept. of Economics (Denmark)

    1996-12-31

    For economic, political, and administrative reasons, a mixed design of permit market, bubble and tax is preferable for CO{sub 2} regulation in Denmark. A CO{sub 2} market should be introduced for the private manufacturing sector in Denmark and an administratively set CO{sub 2} bubble should be introduced for the public electricity sector. Permits are then to be devaluated in year 2005 by 20%. A CO{sub 2} tax should be correctly set at a US dollar 50 level in year 2005 for households, transportation sector and private firms not participating in the CO{sub 2} market. (au) 49 p.

  13. Endothelin-2/Vasoactive Intestinal Contractor: Regulation of Expression via Reactive Oxygen Species Induced by CoCl22, and Biological Activities Including Neurite Outgrowth in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2006-01-01

    Full Text Available This paper reviews the local hormone endothelin-2 (ET-2, or vasoactive intestinal contractor (VIC, a member of the vasoconstrictor ET peptide family, where ET-2 is the human orthologous peptide of the murine VIC. While ET-2/VIC gene expression has been observed in some normal tissues, ET-2 recently has been reported to act as a tumor marker and as a hypoxia-induced autocrine survival factor in tumor cells. A recently published study reported that the hypoxic mimetic agent CoCl2 at 200 µM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced intracellular reactive oxygen species (ROS increase and neurite outgrowth in neuronal model PC12 cells. The ROS was generated by addition of CoCl2 to the culture medium, and the CoCl2-induced effects were completely inhibited by the antioxidant N-acetyl cysteine. Furthermore, interleukin-6 (IL-6 gene expression was up-regulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by CoCl2-induced ROS may be associated with neuronal differentiation through the regulation of IL-6 expression. CoCl2 acts as a pro-oxidant, as do Fe(II, III and Cu(II. However, some biological activities have been reported for CoCl2 that have not been observed for other metal salts such as FeCl3, CuSO4, and NiCl2. The characteristic actions of CoCl2 may be associated with the differentiation of PC12 cells. Further elucidation of the mechanism of neurite outgrowth and regulation of ET-2/VIC expression by CoCl2 may lead to the development of treatments for neuronal disorders.

  14. miRNA-mediated functional changes through co-regulating function related genes.

    Directory of Open Access Journals (Sweden)

    Jie He

    Full Text Available BACKGROUND: MicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation. RESULTS: To explore the internal mechanism of miRNA-mediated regulation, we re-analyzed the data collected from genome-wide miRNA microarray with bioinformatics assay, and found that the transfection of miR-181b and miR-34a in Hela and HCT-116 tumor cells regulated large numbers of genes, among which, the genes related to cell growth and cell death demonstrated high Enrichment scores, suggesting that these miRNAs may be important in cell growth and cell death. MiR-181b induced changes in protein expression of most genes that were seemingly related to enhancing cell growth and decreasing cell death, while miR-34a mediated contrary changes of gene expression. Cell growth assays further confirmed this finding. In further study on miR-20b-mediated osteogenesis in hMSCs, miR-20b was found to enhance osteogenesis by activating BMPs/Runx2 signaling pathway in several stages by co-repressing of PPARγ, Bambi and Crim1. CONCLUSIONS: With its multi-target characteristics, miR-181b, miR-34a and miR-20b provoked detectable functional changes by co-regulating functionally-related gene groups or several genes in the same signaling pathway, and thus mild regulation from individual miRNA targeting genes could have contributed to an additive effect. This might also be one of the modes of miRNA-mediated gene regulation.

  15. NEA activities in safety and regulation

    International Nuclear Information System (INIS)

    Stadie, K.B.

    1983-01-01

    The NEA programme on Safety and Regulations is briefly reviewed. It encompasses four main areas - nuclear safety technology; nuclear licensing; radiation protection; and waste management - with three principal objectives: to promote exchanges of technical information in order to enlarge the data base for national decision making; to improve co-ordination of national R and D activities with emphasis on international standard problem exercises, and to promote international projects; to develop common technical, administrative and legal approaches to improve compatibility of safety and regulatory practices

  16. Characterization and regulation of the bovine stearoyl-CoA desaturase gene promoter

    International Nuclear Information System (INIS)

    Keating, Aileen F.; Kennelly, John J.; Zhao Fengqi

    2006-01-01

    The bovine stearoyl-CoA desaturase (Scd) gene plays an important role in the bovine mammary gland where substrates such as stearic and vaccenic acids are converted to oleic acid and conjugated linoleic acid (CLA), respectively. Up to 90% of the CLA in bovine milk is formed due to the action of this enzyme in the mammary gland. The areas of the bovine promoter of importance in regulating this key enzyme were examined and an area of 36 bp in length was identified as having a critical role in transcriptional activation and is designated the Scd transcriptional enhancer element (STE). Electrophoretic mobility shift assay detected three binding complexes on this area in Mac-T cell nuclear extracts. Treatment of cells with CLA caused a significant reduction in transcriptional activity, with this effect being mediated through the STE region. The bovine Scd gene promoter was up-regulated by insulin and down-regulated by oleic acid

  17. Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

    Science.gov (United States)

    Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

    2016-10-01

    Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Down-regulation of tissue N:P ratios in terrestrial plants by elevated CO2.

    Science.gov (United States)

    Deng, Qi; Hui, Dafeng; Luo, Yiqi; Elser, James; Wang, Ying-ping; Loladze, Irakli; Zhang, Quanfa; Dennis, Sam

    2015-12-01

    Increasing atmospheric CO2 concentrations generally alter element stoichiometry in plants. However, a comprehensive evaluation of the elevated CO2 impact on plant nitrogen: phosphorus (N:P) ratios and the underlying mechanism has not been conducted. We synthesized the results from 112 previously published studies using meta-analysis to evaluate the effects of elevated CO2 on the N:P ratio of terrestrial plants and to explore the underlying mechanism based on plant growth and soil P dynamics. Our results show that terrestrial plants grown under elevated CO2 had lower N:P ratios in both above- and belowground biomass across different ecosystem types. The response ratio for plant N:P was negatively correlated with the response ratio for plant growth in croplands and grasslands, and showed a stronger relationship for P than for N. In addition, the CO2-induced down-regulation of plant N:P was accompanied by 19.3% and 4.2% increases in soil phosphatase activity and labile P, respectively, and a 10.1% decrease in total soil P. Our results show that down-regulation of plant N:P under elevated CO2 corresponds with accelerated soil P cycling. These findings should be useful for better understanding of terrestrial plant stoichiometry in response to elevated CO2 and of the underlying mechanisms affecting nutrient dynamics under climate change.

  19. Wake Me Up Before You CoCo : Implications of contingent convertible capital for financial regulation

    NARCIS (Netherlands)

    Chan, S.

    2017-01-01

    Contingent convertible capital (CoCo) is designed to improve the loss absorption capacity of the issuing bank without resorting to new equity or taxpayer-funded bailouts. However attractive they might seem to the regulator, they may have undesirable and unexpected consequences. This dissertation

  20. Effect of Co crystallinity on Co/CNT catalytic activity in CO/CO{sub 2} hydrogenation and CO disproportionation

    Energy Technology Data Exchange (ETDEWEB)

    Chernyak, Sergei A., E-mail: chernyak.msu@gmail.com [Lomonosov Moscow State University, Department of Chemistry, Leninskiye Gory 1-3, Moscow 119991 (Russian Federation); Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Department of Physical Chemistry, Leninsky Avenue 31, Moscow 119991 (Russian Federation); Suslova, Evgeniya V.; Egorov, Alexander V.; Maslakov, Konstantin I. [Lomonosov Moscow State University, Department of Chemistry, Leninskiye Gory 1-3, Moscow 119991 (Russian Federation); Savilov, Serguei V.; Lunin, Valery V. [Lomonosov Moscow State University, Department of Chemistry, Leninskiye Gory 1-3, Moscow 119991 (Russian Federation); Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Department of Physical Chemistry, Leninsky Avenue 31, Moscow 119991 (Russian Federation)

    2016-05-30

    Highlights: • Amorphous and crystalline Co supported on CNTs were obtained by tuning of CNT surface. • CO and CO{sub 2} hydrogenation does not occur on amorphous Co particles. • Thermal activation of amorphous Co led to crystallization of metal. • Amorphous Co promotes CO disproportionation. • Carbon shells around the amorphous metal particles after the CO hydrogenation. - Abstract: Carbon nanotubes (CNTs) with different degree of surface oxidation were used as supports for 5 wt.% Co catalysts. CNTs and Co/CNT catalysts were analyzed by XPS, nitrogen adsorption, TEM and electron diffraction to reveal their structure. High oxidation degree of CNT surface (8.6 at.% of O) and low Co loading led to predominantly amorphous Co species. This resulted in the absence of catalytic activity in both CO and CO{sub 2} hydrogenation in opposite to the catalyst supported on less oxidized CNTs (5.4 at.% of O) where Co species were found to be crystalline. Thermal treatment of inactive catalyst in H{sub 2} and He led to the formation of Co crystal phase which was active in catalysis. Co particle size in catalyst supported on strongly oxidized CNTs was unchanged during CO hydrogenation in opposite to Co supported on less oxidized CNTs. Carbon shell formation on the surface of amorphous Co particles during CO hydrogenation was revealed, which testified CO disproportionation. Qualitative mechanism of CO hydrogenation on small Co particles was proposed.

  1. PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene expression

    OpenAIRE

    Wang, Juan; Lin, Xueqiu; Wang, Su; Wang, Chenfei; Wang, Qixuan; Duan, Xikun; Lu, Peng; Wang, Qian; Wang, Chengyang; Liu, X. Shirley; Huang, Jinyan

    2014-01-01

    Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8 are associated with X-linked mental retardation. It usually functions as a transcriptional co-activator by associating with H3K4me3 and RNA polymerase II. We found that PHF8 may associat...

  2. P53 activation, a key event of the cellular response to gamma irradiation; L'activation de la proteine p53, un evenement determinant de la reponse cellulaire aux radiations ionisantes

    Energy Technology Data Exchange (ETDEWEB)

    Drane, P.; Alvarez, S.; Meiller, A.; May, E. [CEA Fontenay-aux-Roses, Dept. de Radiobiologie et de Radiopathologie, Lab. de Cancerogenese Moleculaire, CNRS, UMR 217, 92 (France)

    2002-03-01

    The tumor suppressor gene p53 encodes a protein whose major function is to protect organisms from proliferation of potentially tumorigenic cells. In normal conditions (unstressed cells), the p53 protein is inert and maintained at low level through its association with the Mdm2 oncogene, causing its translocation from the nucleus into the cytoplasm and its degradation through ubiquitin/proteasome pathway. In response to damaged DNA or to a variety of stresses, p53 accumulates in the nucleus and is activated as a transcriptional trans-activator. Posttranslational modifications of p53 including multi-site phosphorylation and acetylation are the major mechanism of p53 regulation. After exposure to ionising radiation, p53 activation implicates ATM, ATR, Chk2 and Chk1 kinases that phosphorylate the N-terminal domain on Ser15 (ATM and/or ATR), and Ser20 (Chk2 and/or Chk1), causing the dissociation of the p53/Mdm2 complex and thereby the stabilisation of p53. The process initiated by {gamma}-irradiation exposure involves also increased interaction of the p53 N-terminal domain with CBP/p300 and P/CAF leading to acetylation of the distant C-terminal domain at Lys 320, 373 and 382. In addition, the ATM-mediated dephosphorylation of Ser376 creates a fixation site for 14-3-3 protein. Taken together, phosphorylation, acetylation and association with co factors induce the stimulation of p53 transcriptional activity resulting in the expression of a set of genes involved, notably, in cell cycle arrest and apoptosis. This stress-induced p53 pathways lead to one of two outcomes: growth arrest or apoptosis and consequently protects the organism from the genotoxic effects of ionising radiation. (author)

  3. Regulation of Coordination Number over Single Co Sites: Triggering the Efficient Electroreduction of CO2.

    Science.gov (United States)

    Wang, Xiaoqian; Chen, Zhao; Zhao, Xuyan; Yao, Tao; Chen, Wenxing; You, Rui; Zhao, Changming; Wu, Geng; Wang, Jing; Huang, Weixin; Yang, Jinlong; Hong, Xun; Wei, Shiqiang; Wu, Yuen; Li, Yadong

    2018-02-12

    The design of active, selective, and stable CO 2 reduction electrocatalysts is still challenging. A series of atomically dispersed Co catalysts with different nitrogen coordination numbers were prepared and their CO 2 electroreduction catalytic performance was explored. The best catalyst, atomically dispersed Co with two-coordinate nitrogen atoms, achieves both high selectivity and superior activity with 94 % CO formation Faradaic efficiency and a current density of 18.1 mA cm -2 at an overpotential of 520 mV. The CO formation turnover frequency reaches a record value of 18 200 h -1 , surpassing most reported metal-based catalysts under comparable conditions. Our experimental and theoretical results demonstrate that lower a coordination number facilitates activation of CO 2 to the CO 2 .- intermediate and hence enhances CO 2 electroreduction activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Self-regulation as a type of managerial activity.

    Directory of Open Access Journals (Sweden)

    Anna Algazina

    2017-01-01

    Full Text Available УДК 342.9The subject. In the context of the ongoing administrative reform in the Russian Federation the issue of self-regulation is becoming increasingly important.Introduction of Institute of self-regulation is intended to reduce the degree of state intervention in private spheres of professional activity, to eliminate excessive administrative barriers, reduce government expenditures on regulation and control in their respective areas of operation, which is especially important in the current economic conditions.However, in Russian legal science is no recognized definition of "self-regulation", but a unity of views on the question of the relationship between self-regulation and state regulation of business relations.In this regard, the author attempts to examine the concept of "self-regulation" through the prism of knowledge about public administration.The purpose of the article is to identify the essential features and to articulate the concept of self-regulation by comparing it with other varieties of regulation.Methodology. The methodological basis for the study: general scientific methods (analysis, synthesis, comparison, description; private and academic (interpretation, formal-legal.Results, scope. Based on the analysis allocated in the science of administrative law approaches to the system of public administration justifies the conclusion that the notion "regulation" is specific in relation to the generic concept of "management" and is a kind of management, consisting in the drafting of rules of conduct and sanctions for non-compliance or inadequate performance.In addition, the article highlights the problem of the genesis of self-regulation, building a system of principles of self-regulation, comparison of varieties of self-regulatory organizations among themselves.Conclusions. The comparison of self-regulation other types of regulation (such as state regulation and co-regulation highlighted the essential features of this phenomenon

  5. Plasma membrane calcium ATPase 4 (PMCA4) co-ordinates calcium and nitric oxide signaling in regulating murine sperm functional activity.

    Science.gov (United States)

    Olli, Kristine E; Li, Kun; Galileo, Deni S; Martin-DeLeon, Patricia A

    2018-01-01

    Reduced sperm motility (asthenospermia) and resulting infertility arise from deletion of the Plasma Membrane Ca 2+ -ATPase 4 (Pmca4) gene which encodes the highly conserved Ca 2+ efflux pump, PMCA4. This is the major Ca 2+ clearance protein in murine sperm. Since the mechanism underlying asthenospermia in PMCA4's absence or reduced activity is unknown, we investigated if sperm PMCA4 negatively regulates nitric oxide synthases (NOSs) and when absent NO, peroxynitrite, and oxidative stress levels are increased. Using co-immunoprecipitation (Co-IP) and Fluorescence Resonance Energy Transfer (FRET), we show an association of PMCA4 with the NOSs in elevated cytosolic [Ca 2+ ] in capacitated and Ca 2+ ionophore-treated sperm and with neuronal (nNOS) at basal [Ca 2+ ] (ucapacitated sperm). FRET efficiencies for PMCA4-eNOS were 35% and 23% in capacitated and uncapacitated sperm, significantly (p < 0.01) different, with the molecules being <10 nm apart. For PMCA4-nNOS, this interaction was seen only for capacitated sperm where FRET efficiency was 24%, significantly (p < 0.05) higher than in uncapacitated sperm (6%). PMCA4 and the NOSs were identified as interacting partners in a quaternary complex that includes Caveolin1, which co-immunoprecipitated with eNOS in a Ca 2+ -dependent manner. In Pmca4 -/- sperm NOS activity was elevated twofold in capacitated/uncapacitated sperm (vs. wild-type), accompanied by a twofold increase in peroxynitrite levels and significantly (p < 0.001) increased numbers of apoptotic germ cells. The data support a quaternary complex model in which PMCA4 co-ordinates Ca 2+ and NO signaling to maintain motility, with increased NO levels resulting in asthenospermia in Pmca4 -/- males. They suggest the involvement of PMCA4 mutations in human asthenospermia, with diagnostic relevance. © 2017 Wiley Periodicals, Inc.

  6. AN APPROACH TO SELF- AND CO-REGULATION OF ELECTRONIC COMMERCE IN BUILDING TRUST OVER THE INTERNET

    Directory of Open Access Journals (Sweden)

    R. Serbu

    2016-10-01

    Full Text Available The goal of this paper is to highlights some thoughts about regulation and self-regulation for e-commerce, to present cases and the importance of co- and self-regulation in e-commerce. There are a couple of question that rise in this area and we will try to answer with this paper: What are the benefits and disadvantages of self- and co-regulation, how can online industry be a cause and effect for self and co-regulation, should our web portal and search engines be a subject to any kind of regulation, what is the impact of the Internet and self and co-regulation on the e-commerce.

  7. Genome-wide identification of physically clustered genes suggests chromatin-level co-regulation in male reproductive development in Arabidopsis thaliana.

    Science.gov (United States)

    Reimegård, Johan; Kundu, Snehangshu; Pendle, Ali; Irish, Vivian F; Shaw, Peter; Nakayama, Naomi; Sundström, Jens F; Emanuelsson, Olof

    2017-04-07

    Co-expression of physically linked genes occurs surprisingly frequently in eukaryotes. Such chromosomal clustering may confer a selective advantage as it enables coordinated gene regulation at the chromatin level. We studied the chromosomal organization of genes involved in male reproductive development in Arabidopsis thaliana. We developed an in-silico tool to identify physical clusters of co-regulated genes from gene expression data. We identified 17 clusters (96 genes) involved in stamen development and acting downstream of the transcriptional activator MS1 (MALE STERILITY 1), which contains a PHD domain associated with chromatin re-organization. The clusters exhibited little gene homology or promoter element similarity, and largely overlapped with reported repressive histone marks. Experiments on a subset of the clusters suggested a link between expression activation and chromatin conformation: qRT-PCR and mRNA in situ hybridization showed that the clustered genes were up-regulated within 48 h after MS1 induction; out of 14 chromatin-remodeling mutants studied, expression of clustered genes was consistently down-regulated only in hta9/hta11, previously associated with metabolic cluster activation; DNA fluorescence in situ hybridization confirmed that transcriptional activation of the clustered genes was correlated with open chromatin conformation. Stamen development thus appears to involve transcriptional activation of physically clustered genes through chromatin de-condensation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Regulators of nonsulfur purple phototrophic bacteria and the interactive control of CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy generation.

    Science.gov (United States)

    Dubbs, James M; Tabita, F Robert

    2004-06-01

    For the metabolically diverse nonsulfur purple phototrophic bacteria, maintaining redox homeostasis requires balancing the activities of energy supplying and energy-utilizing pathways, often in the face of drastic changes in environmental conditions. These organisms, members of the class Alphaproteobacteria, primarily use CO2 as an electron sink to achieve redox homeostasis. After noting the consequences of inactivating the capacity for CO2 reduction through the Calvin-Benson-Bassham (CBB) pathway, it was shown that the molecular control of many additional important biological processes catalyzed by nonsulfur purple bacteria is linked to expression of the CBB genes. Several regulator proteins are involved, with the two component Reg/Prr regulatory system playing a major role in maintaining redox poise in these organisms. Reg/Prr was shown to be a global regulator involved in the coordinate control of a number of metabolic processes including CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy-generation pathways. Accumulating evidence suggests that the Reg/Prr system senses the oxidation/reduction state of the cell by monitoring a signal associated with electron transport. The response regulator RegA/PrrA activates or represses gene expression through direct interaction with target gene promoters where it often works in concert with other regulators that can be either global or specific. For the key CO2 reduction pathway, which clearly triggers whether other redox balancing mechanisms are employed, the ability to activate or inactivate the specific regulator CbbR is of paramount importance. From these studies, it is apparent that a detailed understanding of how diverse regulatory elements integrate and control metabolism will eventually be achieved.

  9. The regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase

    DEFF Research Database (Denmark)

    Shi, Xun; Li, Juan; Zou, Xiaoju

    2013-01-01

    Fatty acid desaturation regulates membrane function and fat storage in animals. To determine the contribution of stearoyl-CoA desaturase (SCD) activity on fat storage and development in the nematode Caenorhabditis elegans, we analyzed the lipid composition and lipid droplet size in the fat-6;fat-7...... desaturase mutants, independently, and in combination with mutants disrupted in conserved lipid metabolic pathways. C. elegans with impaired SCD activity displayed both reduced fat stores and decreased lipid droplet size. Mutants in the daf-2 (insulin-like growth factor receptor), rsks-1 (homolog of p70S6......-2;fat-6;fat-7 triple mutants, which had increased de novo fatty acid synthesis and wild type levels of fat stores. Notably, stearoyl-CoA desaturase activity is required for the formation of large-sized lipid droplets in all mutant backgrounds, as well as for normal ratios of phosphatidylcholine (PC...

  10. A general model for CO2 regulation: the case of Denmark

    DEFF Research Database (Denmark)

    Svendsen, Gert Tinggaard

    1998-01-01

    For both economic, political, and administrative reasons, a mixed design of permit market, bubble and tax may be preferable for CO2 regulation. In the case of Denmark, a CO2 market should be introduced for the private manufacturing sector and an administratively set CO2 bubble should be introduced...

  11. Kinetic and Thermodynamic Analysis of Acetyl-CoA Activation of Staphylococcus aureus Pyruvate Carboxylase.

    Science.gov (United States)

    Westerhold, Lauren E; Bridges, Lance C; Shaikh, Saame Raza; Zeczycki, Tonya N

    2017-07-11

    Allosteric regulation of pyruvate carboxylase (PC) activity is pivotal to maintaining metabolic homeostasis. In contrast, dysregulated PC activity contributes to the pathogenesis of numerous diseases, rendering PC a possible target for allosteric therapeutic development. Recent research efforts have focused on demarcating the role of acetyl-CoA, one of the most potent activators of PC, in coordinating catalytic events within the multifunctional enzyme. Herein, we report a kinetic and thermodynamic analysis of acetyl-CoA activation of the Staphylococcus aureus PC (SaPC)-catalyzed carboxylation of pyruvate to identify novel means by which acetyl-CoA synchronizes catalytic events within the PC tetramer. Kinetic and linked-function analysis, or thermodynamic linkage analysis, indicates that the substrates of the biotin carboxylase and carboxyl transferase domain are energetically coupled in the presence of acetyl-CoA. In contrast, both kinetic and energetic coupling between the two domains is lost in the absence of acetyl-CoA, suggesting a functional role for acetyl-CoA in facilitating the long-range transmission of substrate-induced conformational changes within the PC tetramer. Interestingly, thermodynamic activation parameters for the SaPC-catalyzed carboxylation of pyruvate are largely independent of acetyl-CoA. Our results also reveal the possibility that global conformational changes give rise to observed species-specific thermodynamic activation parameters. Taken together, our kinetic and thermodynamic results provide a possible allosteric mechanism by which acetyl-CoA coordinates catalysis within the PC tetramer.

  12. Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters.

    Science.gov (United States)

    Toneff, Thomas; Funkelstein, Lydiane; Mosier, Charles; Abagyan, Armen; Ziegler, Michael; Hook, Vivian

    2013-08-01

    Beta-amyloid (Aβ) peptides are secreted from neurons, resulting in extracellular accumulation of Aβ and neurodegeneration of Alzheimer's disease. Because neuronal secretion is fundamental for the release of neurotransmitters, this study assessed the hypothesis that Aβ undergoes co-release with neurotransmitters. Model neuronal-like chromaffin cells were investigated, and results illustrate regulated, co-secretion of Aβ(1-40) and Aβ(1-42) with peptide neurotransmitters (galanin, enkephalin, and NPY) and catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). Regulated secretion from chromaffin cells was stimulated by KCl depolarization and nicotine. Forskolin, stimulating cAMP, also induced co-secretion of Aβ peptides with peptide and catecholamine neurotransmitters. These data suggested the co-localization of Aβ with neurotransmitters in dense core secretory vesicles (DCSV) that store and secrete such chemical messengers. Indeed, Aβ was demonstrated to be present in DCSV with neuropeptide and catecholamine transmitters. Furthermore, the DCSV organelle contains APP and its processing proteases, β- and γ-secretases, that are necessary for production of Aβ. Thus, Aβ can be generated in neurotransmitter-containing DCSV. Human IMR32 neuroblastoma cells also displayed regulated secretion of Aβ(1-40) and Aβ(1-42) with the galanin neurotransmitter. These findings illustrate that Aβ peptides are present in neurotransmitter-containing DCSV, and undergo co-secretion with neuropeptide and catecholamine neurotransmitters that regulate brain functions. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. CCoAOMT Down-Regulation Activates Anthocyanin Biosynthesis in Petunia.

    Science.gov (United States)

    Shaipulah, Nur Fariza M; Muhlemann, Joëlle K; Woodworth, Benjamin D; Van Moerkercke, Alex; Verdonk, Julian C; Ramirez, Aldana A; Haring, Michel A; Dudareva, Natalia; Schuurink, Robert C

    2016-02-01

    Anthocyanins and volatile phenylpropenes (isoeugenol and eugenol) in petunia (Petunia hybrida) flowers have the precursor 4-coumaryl coenzyme A (CoA) in common. These phenolics are produced at different stages during flower development. Anthocyanins are synthesized during early stages of flower development and sequestered in vacuoles during the lifespan of the flowers. The production of isoeugenol and eugenol starts when flowers open and peaks after anthesis. To elucidate additional biochemical steps toward (iso)eugenol production, we cloned and characterized a caffeoyl-coenzyme A O-methyltransferase (PhCCoAOMT1) from the petals of the fragrant petunia 'Mitchell'. Recombinant PhCCoAOMT1 indeed catalyzed the methylation of caffeoyl-CoA to produce feruloyl CoA. Silencing of PhCCoAOMT1 resulted in a reduction of eugenol production but not of isoeugenol. Unexpectedly, the transgenic plants had purple-colored leaves and pink flowers, despite the fact that cv Mitchell lacks the functional R2R3-MYB master regulator ANTHOCYANIN2 and has normally white flowers. Our results indicate that down-regulation of PhCCoAOMT1 activated the anthocyanin pathway through the R2R3-MYBs PURPLE HAZE (PHZ) and DEEP PURPLE, with predominantly petunidin accumulating. Feeding cv Mitchell flowers with caffeic acid induced PHZ expression, suggesting that the metabolic perturbation of the phenylpropanoid pathway underlies the activation of the anthocyanin pathway. Our results demonstrate a role for PhCCoAOMT1 in phenylpropene production and reveal a link between PhCCoAOMT1 and anthocyanin production. © 2016 American Society of Plant Biologists. All Rights Reserved.

  14. The AMP-activated protein kinase is involved in the regulation of ketone body production by astrocytes.

    Science.gov (United States)

    Blázquez, C; Woods, A; de Ceballos, M L; Carling, D; Guzmán, M

    1999-10-01

    The possible role of the AMP-activated protein kinase (AMPK), a highly conserved stress-activated kinase, in the regulation of ketone body production by astrocytes was studied. AMPK activity in rat cortical astrocytes was three times higher than in rat cortical neurons. AMPK in astrocytes was shown to be functionally active. Thus, incubation of astrocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMPK, stimulated both ketogenesis from palmitate and carnitine palmitoyltransferase I. This was concomitant to a decrease of intracellular malonyl-CoA levels and an inhibition of acetyl-CoA carboxylase/fatty acid synthesis and 3-hydroxy-3-methylglutaryl-CoA reductase/cholesterol synthesis. Moreover, in microdialysis experiments AICAR was shown to stimulate brain ketogenesis markedly. The effect of chemical hypoxia on AMPK and the ketogenic pathway was studied subsequently. Incubation of astrocytes with azide led to a remarkable drop of fatty acid beta-oxidation. However, activation of AMPK during hypoxia compensated the depression of beta-oxidation, thereby sustaining ketone body production. This effect seemed to rely on the cascade hypoxia --> increase of the AMP/ATP ratio --> AMPK stimulation --> acetyl-CoA carboxylase inhibition --> decrease of malonyl-CoA concentration --> carnitine palmitoyltransferase I deinhibition --> enhanced ketogenesis. Furthermore, incubation of neurons with azide blunted lactate oxidation, but not 3-hydroxybutyrate oxidation. Results show that (a) AMPK plays an active role in the regulation of ketone body production by astrocytes, and (b) ketone bodies produced by astrocytes during hypoxia might be a substrate for neuronal oxidative metabolism.

  15. Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression.

    Science.gov (United States)

    Bajaj, V; Lucas, R L; Hwang, C; Lee, C A

    1996-11-01

    During infection of their hosts, salmonellae enter intestinal epithelial cells. It has been proposed that when Salmonella typhimurium is present in the intestinal lumen, several environmental and regulatory conditions modulate the expression of invasion factors required for bacterial entry into host cells. We report here that the expression of six different S. typhimurium invasion genes encoded on SPI1 (Salmonella pathogenicity island 1) is co-ordinately regulated by oxygen, osmolarity, pH, PhoPQ, and HilA. HilA is a transcriptional activator of the OmpR/ToxR family that is also encoded on SPI1. We have found that HilA plays a central role in the co-ordinated regulation of invasion genes by environmental and regulatory conditions. HilA can activate the expression of two invasion gene-lacZY fusions on reporter plasmids in Escherichia coll, suggesting that HilA acts directly at invasion-gene promoters in S. typhimurium. We have found that the regulation of invasion genes by oxygen, osmolarity, pH, and PhoPQ is indirect and is mediated by regulation of hilA expression by these environmental and regulatory factors. We hypothesize that the complex and co-ordinate regulation of Invasion genes by HilA is an important feature of salmonella pathogenesis and allows salmonellae to enter intestinal epithelial cells.

  16. An approach to self- and co-regulation of electronic Commerce in building trust over the Internet

    OpenAIRE

    SERBU R.

    2016-01-01

    The goal of this paper is to highlights some thoughts about regulation and self-regulation for e-commerce, to present cases and the importance of co- and self-regulation in e-commerce. There are a couple of question that rise in this area and we will try to answer with this paper: What are the benefits and disadvantages of self- and co-regulation, how can online industry be a cause and effect for self and co-regulation, should our web portal and search engines be a subject to any kind of regu...

  17. Layers of Self- and Co-Regulation: Teachers Working Collaboratively to Support Adolescents' Self-Regulated Learning through Reading

    Directory of Open Access Journals (Sweden)

    Deborah L. Butler

    2013-01-01

    Full Text Available This paper reports findings from a longitudinal project in which secondary teachers were working collaboratively to support adolescents' self-regulated learning through reading (LTR in subject-area classrooms. We build from prior research to “connect the dots” between teachers' engagement in self- and co-regulated inquiry, associated shifts in classroom practice, and student self-regulation. More specifically, we investigated whether and how teachers working within a community of inquiry were mobilizing research to shape classroom practice and advance student learning. Drawing on evidence from 18 teachers and their respective classrooms, we describe findings related to the following research questions: (1 While engaged in self- and co-regulated inquiry, what types of practices did teachers enact to support LTR in their subject-area classrooms? (2 How did teachers draw on research-based resources to inform practice development? (3 What kinds of practices could be associated with gains in students' self-regulated LTR? In our discussion, we highlight contributions to understanding how teachers can be supported to situate research in authentic classroom environments and about qualities of practices supportive of students' self-regulated LTR. We also identify limitations of this work and important future directions.

  18. Co-ordinate regulation of genes involved in storage lipid mobilization in Arabidopsis thaliana.

    Science.gov (United States)

    Rylott, E L; Hooks, M A; Graham, I A

    2001-05-01

    Molecular genetic approaches in the model plant Arabidopsis thaliana (Col0) are shedding new light on the role and control of the pathways associated with the mobilization of lipid reserves during oilseed germination and post-germinative growth. Numerous independent studies have reported on the expression of individual genes encoding enzymes from the three major pathways: beta-oxidation, the glyoxylate cycle and gluconeogenesis. However, a single comprehensive study of representative genes and enzymes from the different pathways in a single plant species has not been done. Here we present results from Arabidopsis that demonstrate the co-ordinate regulation of gene expression and enzyme activities for the acyl-CoA oxidase- and 3-ketoacyl-CoA thiolase-mediated steps of beta-oxidation, the isocitrate lyase and malate synthase steps of the glyoxylate cycle and the phosphoenolpyruvate carboxykinase step of gluconeogenesis. The mRNA abundance and enzyme activities increase to a peak at stage 2, 48 h after the onset of seed germination, and decline thereafter either to undetectable levels (for malate synthase and isocitrate lyase) or low basal levels (for the genes of beta-oxidation and gluconeogenesis). The co-ordinate induction of all these genes at the onset of germination raises the possibility that a global regulatory mechanism operates to induce the expression of genes associated with the mobilization of storage reserves during the heterotrophic growth period.

  19. The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters.

    Science.gov (United States)

    Salinero, Alicia C; Knoll, Elisabeth R; Zhu, Z Iris; Landsman, David; Curcio, M Joan; Morse, Randall H

    2018-02-01

    The Ty1 retrotransposons present in the genome of Saccharomyces cerevisiae belong to the large class of mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. The retromobility of Ty1 is regulated by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. In spite of its known function in the nucleus, previous studies have implicated Mediator in the regulation of post-translational steps in Ty1 retromobility. To resolve this paradox, we systematically examined the effects of deleting non-essential Mediator subunits on the frequency of Ty1 retromobility and levels of retromobility intermediates. Our findings reveal that loss of distinct Mediator subunits alters Ty1 retromobility positively or negatively over a >10,000-fold range by regulating the ratio of an internal transcript, Ty1i, to the genomic Ty1 transcript. Ty1i RNA encodes a dominant negative inhibitor of Ty1 retromobility that blocks virus-like particle maturation and cDNA synthesis. These results resolve the conundrum of Mediator exerting sweeping control of Ty1 retromobility with only minor effects on the levels of Ty1 genomic RNA and the capsid protein, Gag. Since the majority of characterized intrinsic and extrinsic regulators of Ty1 retromobility do not appear to effect genomic Ty1 RNA levels, Mediator could play a central role in integrating signals that influence Ty1i expression to modulate retromobility.

  20. Validated analytical modeling of diesel engine regulated exhaust CO emission rate

    Directory of Open Access Journals (Sweden)

    Waleed F Faris

    2016-06-01

    Full Text Available Albeit vehicle analytical models are often favorable for explainable mathematical trends, no analytical model has been developed of the regulated diesel exhaust CO emission rate for trucks yet. This research unprecedentedly develops and validates for trucks a model of the steady speed regulated diesel exhaust CO emission rate analytically. It has been found that the steady speed–based CO exhaust emission rate is based on (1 CO2 dissociation, (2 the water–gas shift reaction, and (3 the incomplete combustion of hydrocarbon. It has been found as well that the steady speed–based CO exhaust emission rate based on CO2 dissociation is considerably less than the rate that is based on the water–gas shift reaction. It has also been found that the steady speed–based CO exhaust emission rate based on the water–gas shift reaction is the dominant source of CO exhaust emission. The study shows that the average percentage of deviation of the steady speed–based simulated results from the corresponding field data is 1.7% for all freeway cycles with 99% coefficient of determination at the confidence level of 95%. This deviation of the simulated results from field data outperforms its counterpart of widely recognized models such as the comprehensive modal emissions model and VT-Micro for all freeway cycles.

  1. Muscle Co-activation: Definitions, Mechanisms, and Functions.

    Science.gov (United States)

    Latash, Mark L

    2018-03-28

    The phenomenon of agonist-antagonist muscle co-activation is discussed with respect to its consequences for movement mechanics (such as increasing joint apparent stiffness, facilitating faster movements, and effects on action stability), implication for movement optimization, and involvement of different neurophysiological structures. Effects of co-activation on movement stability are ambiguous and depend on the effector representing a kinematic chain with a fixed origin or free origin. Further, co-activation is discussed within the framework of the equilibrium-point hypothesis and the idea of hierarchical control with spatial referent coordinates. Relations of muscle co-activation to changes in one of the basic commands, the c-command, are discussed and illustrated. A hypothesis is suggested that agonist-antagonist co-activation reflects a deliberate neural control strategy to preserve effector-level control and avoid making it degenerate and facing the necessity to control at the level of signals to individual muscles. This strategy, in particular, allows stabilizing motor actions by co-varied adjustments in spaces of control variables. This hypothesis is able to account for higher levels of co-activation in young healthy persons performing challenging tasks and across various populations with movement impairments.

  2. CCoAOMT Down-Regulation Activates Anthocyanin Biosynthesis in Petunia1

    Science.gov (United States)

    Shaipulah, Nur Fariza M.; Muhlemann, Joëlle K.; Woodworth, Benjamin D.; Van Moerkercke, Alex; Ramirez, Aldana A.; Haring, Michel A.; Schuurink, Robert C.

    2016-01-01

    Anthocyanins and volatile phenylpropenes (isoeugenol and eugenol) in petunia (Petunia hybrida) flowers have the precursor 4-coumaryl coenzyme A (CoA) in common. These phenolics are produced at different stages during flower development. Anthocyanins are synthesized during early stages of flower development and sequestered in vacuoles during the lifespan of the flowers. The production of isoeugenol and eugenol starts when flowers open and peaks after anthesis. To elucidate additional biochemical steps toward (iso)eugenol production, we cloned and characterized a caffeoyl-coenzyme A O-methyltransferase (PhCCoAOMT1) from the petals of the fragrant petunia ‘Mitchell’. Recombinant PhCCoAOMT1 indeed catalyzed the methylation of caffeoyl-CoA to produce feruloyl CoA. Silencing of PhCCoAOMT1 resulted in a reduction of eugenol production but not of isoeugenol. Unexpectedly, the transgenic plants had purple-colored leaves and pink flowers, despite the fact that cv Mitchell lacks the functional R2R3-MYB master regulator ANTHOCYANIN2 and has normally white flowers. Our results indicate that down-regulation of PhCCoAOMT1 activated the anthocyanin pathway through the R2R3-MYBs PURPLE HAZE (PHZ) and DEEP PURPLE, with predominantly petunidin accumulating. Feeding cv Mitchell flowers with caffeic acid induced PHZ expression, suggesting that the metabolic perturbation of the phenylpropanoid pathway underlies the activation of the anthocyanin pathway. Our results demonstrate a role for PhCCoAOMT1 in phenylpropene production and reveal a link between PhCCoAOMT1 and anthocyanin production. PMID:26620524

  3. Solid state synthesis of stoichiometric LiCoO2 from mechanically activated Co-Li2CO3 mixtures

    International Nuclear Information System (INIS)

    Berbenni, Vittorio; Milanese, Chiara; Bruni, Giovanna; Marini, Amedeo

    2006-01-01

    Stoichiometric lithium cobalt oxide (LiCoO 2 ) has been synthesized by solid state reaction of mixtures of the system Co-0.5Li 2 CO 3 after mechanical activation by high energy milling. The differences in the reaction mechanism and in product stoichiometry with respect to what happens when starting from the non activated (physical) system have been brought into evidence by TG analysis. Furthermore it has been shown that stoichiometric LiCoO 2 is obtained by a 200 h annealing of the activated mixture at temperatures as low as 400 deg. C. Finally, it has been revealed that longer activation times (150 h) result in Co oxidation to Co 3 O 4 that, in turn, hampers the formation of stoichiometric LiCoO 2

  4. Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity

    OpenAIRE

    Hammerstrom, Troy G.; Horton, Lori B.; Swick, Michelle C.; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M.

    2014-01-01

    The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthesis operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity, and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-bin...

  5. Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    He Weiming

    2010-07-01

    Full Text Available Abstract Background Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions. Results Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways. Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods. Conclusions Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.

  6. Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

    2017-05-19

    Malonyl-CoA is a precursor of a variety of compounds such as polyketides and flavonoids. In Saccharomyces cerevisiae, malonyl-CoA concentration is tightly regulated and therefore maintained at a very low level, limiting the production of malonyl-CoA-derived chemicals. Here we manipulated the phospholipid synthesis transcriptional regulators to control the malonyl-CoA levels and increase the downstream product. Through manipulating different regulators including Ino2p, Ino4p, Opi1p, and a series of synthetic Ino2p variants, combining with studying the inositol and choline effect, the engineered strain achieved a 9-fold increase of the titer of malonyl-CoA-derived product 3-hydroxypropionic acid, which is among the highest improvement relative to previously reported strategies. Our study provides a new strategy to regulate malonyl-CoA availability and will contribute to the production of other highly valued malonyl-CoA-derived chemicals.

  7. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation

    OpenAIRE

    Malik, Sohail; Roeder, Robert G.

    2010-01-01

    The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action ...

  8. Commission for Energy regulation (CRE) - Activity report june 2008

    International Nuclear Information System (INIS)

    2008-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

  9. Conservation of gene co-regulation in prokaryotes and eukaryotes.

    NARCIS (Netherlands)

    Snel, B.; Bork, P.; Huynen, M.A.

    2002-01-01

    We raise some issues in detecting the conservation (or absence thereof) of co-regulation using gene order; how we think the variations in the cellular network in various species can be studied; and how to determine and interpret the higher order structure in networks of functional relations.

  10. Downstream signaling mechanism of the C-terminal activation domain of transcriptional coactivator CoCoA

    OpenAIRE

    Kim, Jeong Hoon; Yang, Catherine K.; Stallcup, Michael R.

    2006-01-01

    The coiled-coil coactivator (CoCoA) is a transcriptional coactivator for nuclear receptors and enhances nuclear receptor function by the interaction with the bHLH-PAS domain (AD3) of p160 coactivators. The C-terminal activation domain (AD) of CoCoA possesses strong transactivation activity and is required for the coactivator function of CoCoA with nuclear receptors. To understand how CoCoA AD transmits its activating signal to the transcription machinery, we defined specific subregions, amino...

  11. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.

    Science.gov (United States)

    Yahagi, Naoya; Shimano, Hitoshi; Hasegawa, Kiyoshi; Ohashi, Kenichi; Matsuzaka, Takashi; Najima, Yuho; Sekiya, Motohiro; Tomita, Sachiko; Okazaki, Hiroaki; Tamura, Yoshiaki; Iizuka, Yoko; Ohashi, Ken; Nagai, Ryozo; Ishibashi, Shun; Kadowaki, Takashi; Makuuchi, Masatoshi; Ohnishi, Shin; Osuga, Jun-ichi; Yamada, Nobuhiro

    2005-06-01

    Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.

  12. Activities and co-operations in 1990

    International Nuclear Information System (INIS)

    Cai Dunjiu

    1991-01-01

    The items of activities and co-operations in 1990 are listed. It includes the meetings held by CNDC at home, the international meetings held in China, the international meetings, workshop or training course attended by chinese scientists and other activities and co-operations related to CNDC

  13. Model rules and regulations for a global CO2 emissions credit market

    International Nuclear Information System (INIS)

    Sandor, R.L.; Cole, J.B.; Kelly, M.E.

    1994-01-01

    On 21 April 1993, on the occasion of Earth Day, the United States affirmed its commitment to reducing emissions of greenhouse gases to their 1990 levels by the year 2000. In doing so, the United States joined the European Union (EU), Japan, and approximately 141 other countries that had either committed themselves to this international objective or subscribed to the general principles contained in the United Nations Framework Convention on Climate Change, signed at UNCED, Rio de Janeiro, June 1992. The commitment of these three trading groups provides the basis for recommending that a market for tradeable carbon dioxide (CO 2 ) emission entitlements among these groups be implemented as soon as an initial set of rules and regulations can be drafted. The goal of a tradeable CO 2 entitlement or credit market is to lower the cost of limiting emissions. The Costs of CO 2 emission abatement are lowered because the market encourages more emission reductions to be produced by the most efficient resources. The ability easily to selI CO 2 credits created through large emission cuts allows cost recovery by, and incentives for, the most efficient sources of emission reductions. The purpose of this paper is to stimulate debate by providing model rules and regulations for a tradeable CO 2 emission credit market. The trading rules and regulations proposed here are meant to initiate a process whereby participants will iterate toward a final set of rules and regulations. Therefore, our proposal should create a point of departure for further adjustments and transformation to the initial set of recommendations. A specific proposal will be advanced at this point in order to provide a basis for the conceptualization of this global market. Moreover, this specific proposal will help focus dialogue and may provide insight into the general recommendations presented in the balance of this paper

  14. The effects of environmental regulation and technical progress on CO2 Kuznets curve: An evidence from China

    International Nuclear Information System (INIS)

    Yin, Jianhua; Zheng, Mingzheng; Chen, Jian

    2015-01-01

    Based on environmental Kuznets curve theory, a panel data model which takes environmental regulation and technical progress as its moderating factors was developed to analyse the institutional and technical factors that affect the path of low-carbon economic development. The results indicated that there was a CO 2 emission Kuznets curve seen in China. Environmental regulation had a significant moderating effect on the curve, and the inflection of CO 2 emissions could come substantially earlier under stricter environmental regulation. Meanwhile, the impact of technical progress on the low-carbon economic development path had a longer hysteresis effect but restrained CO 2 emission during its increasing stage and accelerated its downward trend during the decreasing stage which was conducive to emission reduction. Strict environmental regulation could force the high-carbon emitting industries to transfer from the eastern regions to the central or the western regions of China, which would make the CO 2 Kuznets curve higher in its increasing stage and lower in its decreasing stage than that under looser regulation. Furthermore, energy efficiency, energy structure, and industrial structure exerted a significant direct impact on CO 2 emissions; we should consider the above factors as essential in the quest for low-carbon economic development. - Highlights: • Estimate moderating effect of environmental regulation and technical progress on EKC. • There was a CO 2 emission Kuznets curve in effect in China. • Environmental regulation presents significant moderating effect on EKC. • Technical progress moderates the relationship between income and CO 2 emissions

  15. Cell cycle regulation of the BRCA1/acetyl-CoA-carboxylase complex.

    Science.gov (United States)

    Ray, H; Suau, F; Vincent, A; Dalla Venezia, N

    2009-01-16

    Germ-line alterations in BRCA1 are associated with an increased susceptibility to breast and ovarian cancer. The BRCA1 protein has been implicated in multiple cellular functions. We have recently demonstrated that BRCA1 reduces acetyl-CoA-carboxylase alpha (ACCA) activity through its phospho-dependent binding to ACCA, and further established that the phosphorylation of the Ser1263 of ACCA is required for this interaction. Here, to gain more insight into the cellular conditions that trigger the BRCA1/ACCA interaction, we designed an anti-pSer1263 antibody and demonstrated that the Ser1263 of ACCA is phosphorylated in vivo, in a cell cycle-dependent manner. We further showed that the interaction between BRCA1 and ACCA is regulated during cell cycle progression. Taken together, our findings reveal a novel mechanism of regulation of ACCA distinct from the previously described phosphorylation of Ser79, and provide new insights into the control of lipogenesis through the cell cycle.

  16. The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation.

    Directory of Open Access Journals (Sweden)

    Claudio Scafoglio

    Full Text Available Checkpoint kinase 2 (Chk2 is a major regulator of DNA damage response and can induce alternative cellular responses: cell cycle arrest and DNA repair or programmed cell death. Here, we report the identification of a new role of Chk2 in transcriptional regulation that also contributes to modulating the balance between survival and apoptosis following DNA damage. We found that Chk2 interacts with members of the NCoR/SMRT transcriptional co-regulator complexes and serves as a functional component of the repressor complex, being required for recruitment of SMRT on the promoter of pro-apoptotic genes upon DNA damage. Thus, the co-repressor SMRT exerts a critical protective action against genotoxic stress-induced caspase activation, repressing a functionally important cohort of pro-apoptotic genes. Amongst them, SMRT is responsible for basal repression of Wip1, a phosphatase that de-phosphorylates and inactivates Chk2, thus affecting a feedback loop responsible for licensing the correct timing of Chk2 activation and the proper execution of the DNA repair process.

  17. Trends in CO2 Emissions from China-Oriented International Marine Transportation Activities and Policy Implications

    Directory of Open Access Journals (Sweden)

    Hualong Yang

    2017-07-01

    Full Text Available The demand for marine transportation and its associated CO2 emissions are growing rapidly as a result of increasing international trade and economic growth. An activity-based approach is developed for forecasting CO2 emissions from the China-oriented international seaborne trade sector. To accurately estimate the aggregated emissions, CO2 emissions are calculated individually for five categories of vessels: crude oil tanker, product tanker, chemical tanker, bulk carrier, and container. A business-as-usual (BAU scenario was developed to describe the current situation without additional mitigation policies, whilst three alternative scenarios were developed to describe scenarios with various accelerated improvements of the key factors. The aggregated CO2 emissions are predicted to reach 419.97 Mt under the BAU scenario, and 258.47 Mt under the optimal case, AD3. These predictions are 4.5 times and 2.8 times that of the aggregated emissions in 2007. Our analysis suggests that regulations for monitoring, reporting, and verifying the activities of vessels should be proposed, in order to quantify the CO2 emissions of marine transportation activities in Chinese territorial waters. In the long-term future, mitigation policies should be employed to reduce CO2 emissions from the marine trade sector and to address the climatic impact of shipping.

  18. A Sensorimotor Signature of the Transition to Conscious Social Perception: Co-regulation of Active and Passive Touch

    Directory of Open Access Journals (Sweden)

    Hiroki Kojima

    2017-10-01

    Full Text Available It is not yet well understood how we become conscious of the presence of other people as being other subjects in their own right. Developmental and phenomenological approaches are converging on a relational hypothesis: my perception of a “you” is primarily constituted by another subject’s attention being directed toward “me.” This is particularly the case when my body is being physically explored in an intentional manner. We set out to characterize the sensorimotor signature of the transition to being aware of the other by re-analyzing time series of embodied interactions between pairs of adults (recorded during a “perceptual crossing” experiment. Measures of turn-taking and movement synchrony were used to quantify social coordination, and transfer entropy was used to quantify direction of influence. We found that the transition leading to one’s conscious perception of the other’s presence was indeed characterized by a significant increase in one’s passive reception of the other’s tactile stimulations. Unexpectedly, one’s clear experience of such passive touch was consistently followed by a switch to active touching of the other, while the other correspondingly became more passive, which suggests that this intersubjective experience was reciprocally co-regulated by both participants.

  19. Transcriptional activity of Pax3 is co-activated by TAZ

    International Nuclear Information System (INIS)

    Murakami, Masao; Tominaga, Junji; Makita, Ryosuke; Uchijima, Yasunobu; Kurihara, Yukiko; Nakagawa, Osamu; Asano, Tomoichiro; Kurihara, Hiroki

    2006-01-01

    Pax3 is a transcription factor which functions in embryonic development and human diseases. In a yeast two-hybrid screen with full-length Pax3 as bait, we isolated a clone encoding transcriptional co-activator with PDZ-binding motif (TAZ) from an E10.5 mouse embryo cDNA library. Co-immunoprecipitation and nuclear co-localization of TAZ with Pax3 suggest that their association is functionally relevant. In situ hybridization revealed TAZ and Pax3 expression to partially overlap in the paraxial mesoderm, limb buds, and the neural tube. In C2C12 myoblast cells and NIH3T3 cells, TAZ enhanced the transcriptional activity of Pax3 on artificial and microphthalmia-associated transcription factor promoter-luciferase constructs, suggesting that TAZ can function as a co-activator of Pax3. Functional interaction between Pax3 and TAZ may provide a clue to clarifying the mechanism by which Pax3 serves as a transcriptional activator during embryogenesis

  20. The CO2nnect activities

    Science.gov (United States)

    Eugenia, Marcu

    2014-05-01

    Climate change is one of the biggest challenges we face today. A first step is the understanding the problem, more exactly what is the challenge and the differences people can make. Pupils need a wide competencies to meet the challenges of sustainable development - including climate change. The CO2nnect activities are designed to support learning which can provide pupils the abilities, skills, attitudes and awareness as well as knowledge and understanding of the issues. The project "Together for a clean and healthy world" is part of "The Global Educational Campaign CO2nnect- CO2 on the way to school" and it was held in our school in the period between February and October 2009. It contained a variety of curricular and extra-curricular activities, adapted to students aged from 11 to 15. These activities aimed to develop in students the necessary skills to understanding man's active role in improving the quality of the environment, putting an end to its degrading process and to reducing the effects of climate changes caused by the human intervention in nature, including transport- a source of CO2 pollution. The activity which I propose can be easily adapted to a wide range of age groups and linked to the curricula of many subjects: - Investigate CO2 emissions from travel to school -Share the findings using an international database -Compare and discuss CO2 emissions -Submit questions to a climate- and transport expert -Partner with other schools -Meet with people in your community to discuss emissions from transport Intended learning outcomes for pupils who participate in the CO2nnect campaign are: Understanding of the interconnected mobility- and climate change issue climate change, its causes and consequences greenhouse-gas emissions from transport and mobility the interlinking of social, environmental, cultural and economic aspects of the local transport system how individual choices and participation can contribute to creating a more sustainable development

  1. Support for the revision of regulation on CO2 emissions from light commercial vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Smokers, R.; Fraga, F.; Verbeek, M.; Willems, F.; Massink, R.; Spreen, J. [TNO, Delft (Netherlands); Norris, J.; Martinez, C. [AEA Technology plc, London (United Kingdom); Kampman, B.; Brinke, L.; Van Essen, H. [CE Delft, Delft (Netherlands); Schilling, S.; Gruhlke, A.; Sander, K. [Institut fuer Oekologie und Politik Oekopol, Hamburg (Netherlands); Breemersch, T.; De Ceuster, G.; Vanherle, K.; Heyndrickx, C. [Transport and Mobility Leuven TML, Leuven (Belgium); Wrigley, S.; O' Brien, S.; Johnson, A. [Ricardo UK, Shoreham-by-Sea, West Sussex (United Kingdom); Buttigieg, D.; Sima, L.; Pagnac, J.; Dhaene, G. [IHS Global Insight, Nijmegen (Netherlands)

    2012-04-15

    Road vehicles make a major contribution to transport sector CO2 emissions and the European Union has several policies in place to reduce their emissions. One of these is the regulation to reduce the CO2 emissions of light commercial vehicles (LCVs or vans), Regulation (EU) 510/2011, often referred to as the vans regulation. This contains a number of review clauses, which require the European Commission to carry out an impact assessment on the 2020 target of 147 gCO2/km, and to assess a number of further issues. The ensuing study addresses a wide range of topics relating to this regulation, and includes the development of cost curves for different LCV segments, the evaluation of different utility parameters, a comparison with the effort needed to reduce the CO2 emissions of passenger cars, an assessment of the impact of electric vehicle penetration and calculation of the effects on the total cost of ownership and the societal abatement costs associated with the 2020 target. CE Delft contributed to this study by developing scenarios for the market uptake of electric vehicles in this vehicle segment, and by providing support to the Commission regarding the economic aspects of the Impact Analysis.

  2. CISH is induced during DC development and regulates DC-mediated CTL activation.

    Science.gov (United States)

    Miah, Mohammad Alam; Yoon, Cheol-Hee; Kim, Joonoh; Jang, Jinah; Seong, Young-Rim; Bae, Yong-Soo

    2012-01-01

    The cytokine inducible SH2-domain protein (CISH) is a well-known STAT5 target gene, but its role in the immune system remains uncertain. In this study, we found that CISH is predominantly induced during dendritic cell (DC) development from mouse bone marrow (BM) cells and plays a crucial role in type 1 DC development and DC-mediated CTL activation. CISH knockdown reduced the expression of MHC class I, co-stimulatory molecules and pro-inflammatory cytokines in BMDCs. Meanwhile, the DC yield was markedly enhanced by CISH knockdown via cell-cycle activation and reduction of cell apoptosis. Down-regulation of cell proliferation at the later stage of DC development was found to be associated with CISH-mediated negative feedback regulation of STAT5 activation. In T-cell immunity, OT-1 T-cell proliferation was significantly reduced by CISH knockdown in DCs, whereas OT-2 T-cell proliferation was not affected by CISH knockdown. CTLs generated by DC vaccination were also markedly reduced by CISH knockdown, followed by significant impairment of DC-based tumor immunotherapy. Taken together, our data suggest that CISH expression at the later stage of DC development triggers the shutdown of DC progenitor cell proliferation and facilitates DC differentiation into a potent stimulator of CTLs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

    DEFF Research Database (Denmark)

    Ferreira, Natalia Santos; Engelsby, Hanne; Neess, Ditte

    2017-01-01

    and cardiovascular diseases, as well as neurological disorders. Here we show that acyl-coenzyme A-binding protein (ACBP) potently facilitates very-long acyl chain ceramide synthesis. ACBP increases the activity of ceramide synthase 2 (CerS2) by more than 2-fold and CerS3 activity by 7-fold. ACBP binds very......-long-chain acyl-CoA esters, which is required for its ability to stimulate CerS activity. We also show that high-speed liver cytosol from wild-type mice activates CerS3 activity, whereas cytosol from ACBP knock-out mice does not. Consistently, CerS2 and CerS3 activities are significantly reduced in the testes...... of ACBP(-/-) mice, concomitant with a significant reduction in long- and very-long-chain ceramide levels. Importantly, we show that ACBP interacts with CerS2 and CerS3. Our data uncover a novel mode of regulation of very-long acyl chain ceramide synthesis by ACBP, which we anticipate is of crucial...

  4. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

    Science.gov (United States)

    Lin, Jiandie; Wu, Hai; Tarr, Paul T; Zhang, Chen-Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F; Puigserver, Pere; Isotani, Eiji; Olson, Eric N; Lowell, Bradford B; Bassel-Duby, Rhonda; Spiegelman, Bruce M

    2002-08-15

    The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination.

  5. Regulators of Slc4 bicarbonate transporter activity

    Directory of Open Access Journals (Sweden)

    Ian M. Thornell

    2015-06-01

    Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

  6. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

    Science.gov (United States)

    Nautiyal, Jaya; Steel, Jennifer H; Mane, Meritxell Rosell; Oduwole, Olayiwola; Poliandri, Ariel; Alexi, Xanthippi; Wood, Nicholas; Poutanen, Matti; Zwart, Wilbert; Stingl, John; Parker, Malcolm G

    2013-03-01

    Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

  7. LCGbase: A Comprehensive Database for Lineage-Based Co-regulated Genes.

    Science.gov (United States)

    Wang, Dapeng; Zhang, Yubin; Fan, Zhonghua; Liu, Guiming; Yu, Jun

    2012-01-01

    Animal genes of different lineages, such as vertebrates and arthropods, are well-organized and blended into dynamic chromosomal structures that represent a primary regulatory mechanism for body development and cellular differentiation. The majority of genes in a genome are actually clustered, which are evolutionarily stable to different extents and biologically meaningful when evaluated among genomes within and across lineages. Until now, many questions concerning gene organization, such as what is the minimal number of genes in a cluster and what is the driving force leading to gene co-regulation, remain to be addressed. Here, we provide a user-friendly database-LCGbase (a comprehensive database for lineage-based co-regulated genes)-hosting information on evolutionary dynamics of gene clustering and ordering within animal kingdoms in two different lineages: vertebrates and arthropods. The database is constructed on a web-based Linux-Apache-MySQL-PHP framework and effective interactive user-inquiry service. Compared to other gene annotation databases with similar purposes, our database has three comprehensible advantages. First, our database is inclusive, including all high-quality genome assemblies of vertebrates and representative arthropod species. Second, it is human-centric since we map all gene clusters from other genomes in an order of lineage-ranks (such as primates, mammals, warm-blooded, and reptiles) onto human genome and start the database from well-defined gene pairs (a minimal cluster where the two adjacent genes are oriented as co-directional, convergent, and divergent pairs) to large gene clusters. Furthermore, users can search for any adjacent genes and their detailed annotations. Third, the database provides flexible parameter definitions, such as the distance of transcription start sites between two adjacent genes, which is extendable to genes that flanking the cluster across species. We also provide useful tools for sequence alignment, gene

  8. Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity

    International Nuclear Information System (INIS)

    Jian Yongzhi; Yan Jun; Wang Hanzhou; Chen Chen; Sun Maoyun; Jiang Jianhai; Lu Jieqiong; Yang Yanzhong; Gu Jianxin

    2005-01-01

    D-type cyclins are essential for the progression through the G1 phase of the cell cycle. Besides serving as cell cycle regulators, D-type cyclins were recently reported to have transcription regulation functions. Here, we report that cyclin D3 is a new interacting partner of vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the fat-soluble vitamins A and D. The interaction was confirmed with methods of yeast two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation. Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal microscopy analysis showed that ligand-activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These findings provide us a new clue to understand the transcription regulation functions of D-type cyclins

  9. Carbon dioxide-dependent regulation of NF-κB family members RelB and p100 gives molecular insight into CO2-dependent immune regulation.

    Science.gov (United States)

    Keogh, Ciara E; Scholz, Carsten C; Rodriguez, Javier; Selfridge, Andrew C; von Kriegsheim, Alexander; Cummins, Eoin P

    2017-07-07

    CO 2 is a physiological gas normally produced in the body during aerobic respiration. Hypercapnia (elevated blood pCO 2 >≈50 mm Hg) is a feature of several lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is associated with increased susceptibility to bacterial infections and suppression of inflammatory signaling. The NF-κB pathway has been implicated in these effects; however, the molecular mechanisms underpinning cellular sensitivity of the NF-κB pathway to CO 2 are not fully elucidated. Here, we identify several novel CO 2 -dependent changes in the NF-κB pathway. NF-κB family members p100 and RelB translocate to the nucleus in response to CO 2 A cohort of RelB protein-protein interactions ( e.g. with Raf-1 and IκBα) are altered by CO 2 exposure, although others are maintained ( e.g. with p100). RelB is processed by CO 2 in a manner dependent on a key C-terminal domain located in its transactivation domain. Loss of the RelB transactivation domain alters NF-κB-dependent transcriptional activity, and loss of p100 alters sensitivity of RelB to CO 2 Thus, we provide molecular insight into the CO 2 sensitivity of the NF-κB pathway and implicate altered RelB/p100-dependent signaling in the CO 2 -dependent regulation of inflammatory signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Translational co-regulation of a ligand and inhibitor by a conserved RNA element

    DEFF Research Database (Denmark)

    Zaucker, Andreas; Nagorska, Agnieszka; Kumari, Pooja

    2018-01-01

    In many organisms, transcriptional and post-transcriptional regulation of components of pathways or processes has been reported. However, to date, there are few reports of translational co-regulation of multiple components of a developmental signaling pathway. Here, we show that an RNA element wh...

  11. Co-regulation of metabolic genes is better explained by flux coupling than by network distance.

    Directory of Open Access Journals (Sweden)

    Richard A Notebaart

    2008-01-01

    Full Text Available To what extent can modes of gene regulation be explained by systems-level properties of metabolic networks? Prior studies on co-regulation of metabolic genes have mainly focused on graph-theoretical features of metabolic networks and demonstrated a decreasing level of co-expression with increasing network distance, a naïve, but widely used, topological index. Others have suggested that static graph representations can poorly capture dynamic functional associations, e.g., in the form of dependence of metabolic fluxes across genes in the network. Here, we systematically tested the relative importance of metabolic flux coupling and network position on gene co-regulation, using a genome-scale metabolic model of Escherichia coli. After validating the computational method with empirical data on flux correlations, we confirm that genes coupled by their enzymatic fluxes not only show similar expression patterns, but also share transcriptional regulators and frequently reside in the same operon. In contrast, we demonstrate that network distance per se has relatively minor influence on gene co-regulation. Moreover, the type of flux coupling can explain refined properties of the regulatory network that are ignored by simple graph-theoretical indices. Our results underline the importance of studying functional states of cellular networks to define physiologically relevant associations between genes and should stimulate future developments of novel functional genomic tools.

  12. Commission de regulation de l'energie. Activity Report 2009

    International Nuclear Information System (INIS)

    2010-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2009 activity report of CRE. Content: A - How the CRE works and the activity of the CoRDiS; B - Implementation of the third energy package will strengthen regulation in this sector; C - The regulator contributes to the correct operation of the infrastructures, the interconnection of European grids and security of supplies; D - Regulation: serving investment and quality; E - Renewable energy, advanced metering systems and the grids of the future are all priority means of delivering sustainable development; F - The CRE is contributing to the smooth operation of electricity and gas markets to the benefit of consumers; G - Appendices: 1. Summary of the principal deliberations of the CRE; 2. European and international calendar for 2009; 3. Council of European Energy Regulators (CEER); 4. Glossary; 5. Acronyms; 6. Units and conversions; 7. Index; 8. List of boxes, figures and tables

  13. AMPK activation represses the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase: Role of nuclear respiratory factor-1

    Energy Technology Data Exchange (ETDEWEB)

    Adam, Tasneem; Opie, Lionel H. [Hatter Cardiovascular Research Institute, Faculty of Health Sciences, University of Cape Town, Observatory 7925 (South Africa); Essop, M. Faadiel, E-mail: mfessop@sun.ac.za [Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7600 (South Africa)

    2010-07-30

    Research highlights: {yields} AMPK inhibits acetyl-CoA carboxylase beta gene promoter activity. {yields} Nuclear respiratory factor-1 inhibits acetyl-CoA carboxylase beta promoter activity. {yields} AMPK regulates acetyl-CoA carboxylase beta at transcriptional level. -- Abstract: The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC{beta}) produces malonyl-CoA, a potent inhibitor of carnitine palmitoyltransferase-1. AMPK inhibits ACC{beta} activity, lowering malonyl-CoA levels and promoting mitochondrial fatty acid {beta}-oxidation. Previously, AMPK increased promoter binding of nuclear respiratory factor-1 (NRF-1), a pivotal transcriptional modulator controlling gene expression of mitochondrial proteins. We therefore hypothesized that NRF-1 inhibits myocardial ACC{beta} promoter activity via AMPK activation. A human ACC{beta} promoter-luciferase construct was transiently transfected into neonatal cardiomyocytes {+-} a NRF-1 expression construct. NRF-1 overexpression decreased ACC{beta} gene promoter activity by 71 {+-} 4.6% (p < 0.001 vs. control). Transfections with 5'-end serial promoter deletions revealed that NRF-1-mediated repression of ACC{beta} was abolished with a pPII{beta}-18/+65-Luc deletion construct. AMPK activation dose-dependently reduced ACC{beta} promoter activity, while NRF-1 addition did not further decrease it. We also investigated NRF-1 inhibition in the presence of upstream stimulatory factor 1 (USF1), a known transactivator of the human ACC{beta} gene promoter. Here NRF-1 blunted USF1-dependent induction of ACC{beta} promoter activity by 58 {+-} 7.5% (p < 0.001 vs. control), reversed with a dominant negative NRF-1 construct. NRF-1 also suppressed endogenous USF1 transcriptional activity by 55 {+-} 6.2% (p < 0.001 vs. control). This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACC{beta} gene promoter in the mammalian heart. Our data extends AMPK regulation of ACC{beta} to the transcriptional level.

  14. A complex interplay between PGC-1 co-activators and mTORC1 regulates hematopoietic recovery following 5-fluorouracil treatment

    Directory of Open Access Journals (Sweden)

    Sunanda Basu

    2014-01-01

    Full Text Available In vitro stimulation of HSCs with growth factors generally leads to their depletion. Understanding the molecular mechanisms underlying expansion of HSCs in vivo following myeloablation could lead to successful expansion of HSCs ex vivo for therapeutic purposes. Current findings show that mTORC1 is activated in HSPCs following 5-fluorouracil treatment and that mTORC1 activation is dependent on mitochondrial ETC capacity of HSPCs. Moreover, expression of PGC-1 family members, proteins that regulate mitochondrial biogenesis, in HSPCs following 5-fluorouracil treatment changes; also, these proteins play a stage specific role in hematopoietic recovery. While PRC regulates HSCs' expansion during early recovery phase, PGC-1α regulates progenitor cell proliferation and recovery of hematopoiesis during later phase. During early recovery phase, PRC expression, mitochondrial activity and mTORC1 activation are relatively higher in PGC-1α−/− HSCs compared to WT HSCs, and PGC-1α−/− HSCs show greater expansion. Administration of rapamycin, but not NAC, during early recovery phase improves WT HSC numbers but decreases PGC-1α−/− HSC numbers. The current findings demonstrate that mTOR activation can increase HSC numbers provided that the energy demand created by mTOR activation is successfully met. Thus, critical tuning between mTORC1 activation and mitochondrial ETC capacity is crucial for HSC maintenance/expansion in response to mitogenic stimulation.

  15. Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

    Science.gov (United States)

    Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

    2004-07-01

    Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to

  16. Carbonic anhydrases are upstream regulators of CO2-controlled stomatal movements in guard cells

    KAUST Repository

    Hu, Honghong

    2009-12-13

    The continuing rise in atmospheric CO2 causes stomatal pores in leaves to close and thus globally affects CO2 influx into plants, water use efficiency and leaf heat stress. However, the CO2-binding proteins that control this response remain unknown. Moreover, which cell type responds to CO2, mesophyll or guard cells, and whether photosynthesis mediates this response are matters of debate. We demonstrate that Arabidopsis thaliana double-mutant plants in the beta-carbonic anhydrases betaCA1 and betaCA4 show impaired CO2-regulation of stomatal movements and increased stomatal density, but retain functional abscisic-acid and blue-light responses. betaCA-mediated CO2-triggered stomatal movements are not, in first-order, linked to whole leaf photosynthesis and can function in guard cells. Furthermore, guard cell betaca-overexpressing plants exhibit instantaneous enhanced water use efficiency. Guard cell expression of mammalian alphaCAII complements the reduced sensitivity of ca1 ca4 plants, showing that carbonic anhydrase-mediated catalysis is an important mechanism for betaCA-mediated CO2-induced stomatal closure and patch clamp analyses indicate that CO2/HCO3- transfers the signal to anion channel regulation. These findings, together with ht1-2 (ref. 9) epistasis analysis demonstrate that carbonic anhydrases function early in the CO2 signalling pathway, which controls gas-exchange between plants and the atmosphere.

  17. Activation measurements for thermal neutrons. Part A. Cobalt (60Co) activation

    International Nuclear Information System (INIS)

    Kerr, George D.; Shizuma, Kiyoshi; Endo, Satoru; Maruyama, Takashi; Cullings, Harry M.; Komura, Kazuhisa; Okumura, Yutaka; Egbert, Stephen D.

    2005-01-01

    The 60 Co measurements at Hiroshima and Nagasaki were reviewed and compared with the results of the new DS02 calculations for the two cities. Some corrections were made to previously published data from the 1965 measurements of JNIRS, ground ranges of all of the 60 Co measurements were reviewed and new ground ranges were determined when possible by transforming sample coordinates to the new city maps for Hiroshima and Nagasaki, and transmission factors were investigated for a number of samples used in the 60 Co measurements. Transmission factors were not calculated for all samples used in the 60 Co measurements but some general rules were given for estimating transmission factors for these samples. Experimental measurements of the background 60 Co activity from environmental neutrons were also reviewed, and it was found that the 60 Co background from environmental neutrons was not an important factor in the 60 Co measurements of bomb-induced activity at either city. (J.P.N.)

  18. Effect of dietary and hormonal alterations on the activity of 3-methylcrotonyl-CoA carboylase in rat liver

    International Nuclear Information System (INIS)

    Paul, H.S.; Gleditsch, C.E.; Adibi, S.A.

    1986-01-01

    Previous studies have established that activities of leucine transaminase and branched-chain keto acid dehydrogenase (BCKDH) are under metabolic control. In the present experiment, the authors have investigated whether activity of 3-methylcrotonyl-CoA carboxylase (MCase), an enzyme distal to BCKDH in pathways of leucine oxidation, is also subjected to metabolic regulation. Initially, they developed optimal conditions to assay the activity of this enzyme. The assay was based on the incorporation of 14 CO 2 into 3-methylcrotonyl-CoA (MC-CoA) by liver mitochondria and required the presence of ATP and biotin. Subsequently, the authors determined the activity (nmol 14 CO 2 incorporated/mg protein/min, mean +/- SE, 6 rats) of MCase under normal (2.80 +/- 0.09) and altered conditions. The activity of MCase was not affected either by starvation (2.88 +/- 0.13), diabetes (2.95 +/- 0.11), low-protein (2.35 +/- 0.05), or high-protein diet (3.06 +/- 0.06). To further substantiate these results, they measured accumulation of MC-CoA by incubating liver mitochondria with α-ketoisocaproate (KIC). Of the KIC fraction that underwent flux through BCKDH (2.15 +/- 0.14 nmol/mg protein/min), only 0.26% accumulated as MC-CoA. Even if diabetes, when the flux through BCKDH was significantly increased (3.62 +/- 0.36), the accumulation of MC-CoA was negligible (0.33%). The authors conclude that a) MCase activity does not change in response to dietary and hormonal alterations, and b) MCase is not a rate-limiting reaction in pathways of leucine oxidation

  19. Effect of dietary and hormonal alterations on the activity of 3-methylcrotonyl-CoA carboylase in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Paul, H.S.; Gleditsch, C.E.; Adibi, S.A.

    1986-05-01

    Previous studies have established that activities of leucine transaminase and branched-chain keto acid dehydrogenase (BCKDH) are under metabolic control. In the present experiment, the authors have investigated whether activity of 3-methylcrotonyl-CoA carboxylase (MCase), an enzyme distal to BCKDH in pathways of leucine oxidation, is also subjected to metabolic regulation. Initially, they developed optimal conditions to assay the activity of this enzyme. The assay was based on the incorporation of /sup 14/CO/sub 2/ into 3-methylcrotonyl-CoA (MC-CoA) by liver mitochondria and required the presence of ATP and biotin. Subsequently, the authors determined the activity (nmol /sup 14/CO/sub 2/ incorporated/mg protein/min, mean +/- SE, 6 rats) of MCase under normal (2.80 +/- 0.09) and altered conditions. The activity of MCase was not affected either by starvation (2.88 +/- 0.13), diabetes (2.95 +/- 0.11), low-protein (2.35 +/- 0.05), or high-protein diet (3.06 +/- 0.06). To further substantiate these results, they measured accumulation of MC-CoA by incubating liver mitochondria with ..cap alpha..-ketoisocaproate (KIC). Of the KIC fraction that underwent flux through BCKDH (2.15 +/- 0.14 nmol/mg protein/min), only 0.26% accumulated as MC-CoA. Even if diabetes, when the flux through BCKDH was significantly increased (3.62 +/- 0.36), the accumulation of MC-CoA was negligible (0.33%). The authors conclude that a) MCase activity does not change in response to dietary and hormonal alterations, and b) MCase is not a rate-limiting reaction in pathways of leucine oxidation.

  20. The Co-regulation Data Harvester: Automating gene annotation starting from a transcriptome database

    Science.gov (United States)

    Tsypin, Lev M.; Turkewitz, Aaron P.

    Identifying co-regulated genes provides a useful approach for defining pathway-specific machinery in an organism. To be efficient, this approach relies on thorough genome annotation, a process much slower than genome sequencing per se. Tetrahymena thermophila, a unicellular eukaryote, has been a useful model organism and has a fully sequenced but sparsely annotated genome. One important resource for studying this organism has been an online transcriptomic database. We have developed an automated approach to gene annotation in the context of transcriptome data in T. thermophila, called the Co-regulation Data Harvester (CDH). Beginning with a gene of interest, the CDH identifies co-regulated genes by accessing the Tetrahymena transcriptome database. It then identifies their closely related genes (orthologs) in other organisms by using reciprocal BLAST searches. Finally, it collates the annotations of those orthologs' functions, which provides the user with information to help predict the cellular role of the initial query. The CDH, which is freely available, represents a powerful new tool for analyzing cell biological pathways in Tetrahymena. Moreover, to the extent that genes and pathways are conserved between organisms, the inferences obtained via the CDH should be relevant, and can be explored, in many other systems.

  1. Dynamic regulation of Drosophila nuclear receptor activity in vivo.

    Science.gov (United States)

    Palanker, Laura; Necakov, Aleksandar S; Sampson, Heidi M; Ni, Ruoyu; Hu, Chun; Thummel, Carl S; Krause, Henry M

    2006-09-01

    Nuclear receptors are a large family of transcription factors that play major roles in development, metamorphosis, metabolism and disease. To determine how, where and when nuclear receptors are regulated by small chemical ligands and/or protein partners, we have used a 'ligand sensor' system to visualize spatial activity patterns for each of the 18 Drosophila nuclear receptors in live developing animals. Transgenic lines were established that express the ligand binding domain of each nuclear receptor fused to the DNA-binding domain of yeast GAL4. When combined with a GAL4-responsive reporter gene, the fusion proteins show tissue- and stage-specific patterns of activation. We show that these responses accurately reflect the presence of endogenous and exogenously added hormone, and that they can be modulated by nuclear receptor partner proteins. The amnioserosa, yolk, midgut and fat body, which play major roles in lipid storage, metabolism and developmental timing, were identified as frequent sites of nuclear receptor activity. We also see dynamic changes in activation that are indicative of sweeping changes in ligand and/or co-factor production. The screening of a small compound library using this system identified the angular psoralen angelicin and the insect growth regulator fenoxycarb as activators of the Ultraspiracle (USP) ligand-binding domain. These results demonstrate the utility of this system for the functional dissection of nuclear receptor pathways and for the development of new receptor agonists and antagonists that can be used to modulate metabolism and disease and to develop more effective means of insect control.

  2. Theory of gastric CO2 ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO2 retention.

    Science.gov (United States)

    Dean, Jay B

    2011-02-15

    The theory of gastric CO(2) ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO(2) during respiratory acidosis. Neurons in the cSC, which is a site of CO(2) chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO(2) from blood. CO(2) is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO(2) in the stomach lumen from the reaction between H(+) and HCO(3)(-). Respiratory acidosis and gastric CO(2) distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO(2) upwards by bulk flow along an abdominal-to-esophageal (=intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO(2) is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO(2) ventilation provides explanations for (1) the postprandial increase in expired CO(2) and (2) the negative P(blood - expired)CO₂difference that occurs with increased inspired CO(2). Furthermore, it is postulated that gastric CO(2) ventilation and alveolar CO(2) ventilation are coordinated under dual control by CO(2) chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO(2) chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO(2) elimination. A distributed CO(2

  3. A Carbonic Anhydrase Serves as an Important Acid-Base Regulator in Pacific Oyster Crassostrea gigas Exposed to Elevated CO2: Implication for Physiological Responses of Mollusk to Ocean Acidification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Qiu, Limei; Wang, Lingling; Zhang, Anguo; Song, Linsheng

    2017-02-01

    Carbonic anhydrases (CAs) have been demonstrated to play an important role in acid-base regulation in vertebrates. However, the classification and modulatory function of CAs in marine invertebrates, especially their responses to ocean acidification remain largely unknown. Here, a cytosolic α-CA (designated as CgCAII-1) was characterized from Pacific oyster Crassostrea gigas and its molecular activities against CO 2 exposure were investigated. CgCAII-1 possessed a conserved CA catalytic domain, with high similarity to invertebrate cytoplasmic or mitochondrial α-CAs. Recombinant CgCAII-1 could convert CO 2 to HCO 3 - with calculated activity as 0.54 × 10 3  U/mg, which could be inhibited by acetazolamide (AZ). The mRNA transcripts of CgCAII-1 in muscle, mantle, hepatopancreas, gill, and hemocytes increased significantly after exposure to elevated CO 2 . CgCAII-1 could interact with the hemocyte membrane proteins and the distribution of CgCAII-1 protein became more concentrated and dense in gill and mantle under CO 2 exposure. The intracellular pH (pHi) of hemocytes under CO 2 exposure increased significantly (p ocean acidification and participate in acid-base regulation. Such cytoplasmic CA-based physiological regulation mechanism might explain other physiological responses of marine organisms to OA.

  4. CO2 activation on bimetallic CuNi nanoparticles

    Directory of Open Access Journals (Sweden)

    Natalie Austin

    2016-10-01

    Full Text Available Density functional theory calculations have been performed to investigate the structural, electronic, and CO2 adsorption properties of 55-atom bimetallic CuNi nanoparticles (NPs in core-shell and decorated architectures, as well as of their monometallic counterparts. Our results revealed that with respect to the monometallic Cu55 and Ni55 parents, the formation of decorated Cu12Ni43 and core-shell Cu42Ni13 are energetically favorable. We found that CO2 chemisorbs on monometallic Ni55, core-shell Cu13Ni42, and decorated Cu12Ni43 and Cu43Ni12, whereas, it physisorbs on monometallic Cu55 and core-shell Cu42Ni13. The presence of surface Ni on the NPs is key in strongly adsorbing and activating the CO2 molecule (linear to bent transition and elongation of C˭O bonds. This activation occurs through a charge transfer from the NPs to the CO2 molecule, where the local metal d-orbital density localization on surface Ni plays a pivotal role. This work identifies insightful structure-property relationships for CO2 activation and highlights the importance of keeping a balance between NP stability and CO2 adsorption behavior in designing catalytic bimetallic NPs that activate CO2.

  5. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Xinwei Li

    Full Text Available The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid and BML-275 (an AMPKα inhibitor. Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

  6. Regulation of ROCK Activity in Cancer

    DEFF Research Database (Denmark)

    Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

    2013-01-01

    , these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

  7. CO2 reuse. State of the art and expert opinion. Case of waste treatment activities. Extended abstract

    International Nuclear Information System (INIS)

    Dumergues, L.; Favier, B.; Alvaro Claver, R.

    2014-09-01

    CO 2 emitted from anthropic activities, is perceived as a weakness (e.g. taxes, environmental regulations, impact on global warming... ). However, in a perspective of circular economy, to re-use CO 2 appears to be obvious. Currently, more than about 150 millions of tons of CO 2 are used by industry worldwide. In France, estimates of CO 2 emissions related to the activity 'waste treatment' are up to several tens of millions of tons according to emission inventories. The CO 2 can be used in many ways. The direct use without transformation is undoubtedly one of the most currently applied by the industry and the oil activities for many years. However, the potential development is limited. The chemical conversion of CO 2 used as a 'chemical reactive' is achievable by different techniques: mineralization, organic synthesis, hydrogenation, dry reforming, electrolysis, thermolysis... The products obtained have applications such as energy products, chemicals, building materials,... The developments of some of these techniques are particularly followed by the scientific and industrial community. This is the case of 'methanation' or 'power to gas' allowing potentially use the CO 2 directly out of landfill sites and convert it in 'renewable' methane. The biological use of CO 2 as a nutrient to organisms that perform photosynthesis (eg algae), has several advantages including the possibility to use directly the 'poor CO 2 quality' from the incinerator exhaust. (authors)

  8. Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity.

    Science.gov (United States)

    Hammerstrom, Troy G; Horton, Lori B; Swick, Michelle C; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M

    2015-02-01

    The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO(2)/bicarbonate, and there is a positive correlation between the CO(2)/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His→Asp) and phosphoablative (His→Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism. © 2014 John Wiley & Sons Ltd.

  9. NMR characterization of altered lignins extracted from tobacco plants down-regulated for lignification enzymes cinnamylalcohol dehydrogenase and cinnamoyl-CoA reductase

    OpenAIRE

    Ralph, John; Hatfield, Ronald D.; Piquemal, Joël; Yahiaoui, Nabila; Pean, Michel; Lapierre, Catherine; Boudet, Alain M.

    1998-01-01

    Homologous antisense constructs were used to down-regulate tobacco cinnamyl-alcohol dehydrogenase (CAD; EC 1.1.1.195) and cinnamoyl-CoA reductase (CCR; EC 1.2.1.44) activities in the lignin monomer biosynthetic pathway. CCR converts activated cinnamic acids (hydroxycinnamoyl–SCoAs) to cinnamaldehydes; cinnamaldehydes are then reduced to cinnamyl alcohols by CAD. The transformations caused the incorporation of nontraditional components into the extractable tobacco lignins, as evidenced by NMR....

  10. Role of the N-terminal activation domain of coactivator CoCoA in mediating transcriptional activation by β-catenin*

    OpenAIRE

    Yang, Catherine K.; Kim, Jeong Hoon; Stallcup, Michael R.

    2006-01-01

    The coiled-coil coactivator (CoCoA) is involved in transcriptional activation of target genes by nuclear receptors and the xenobiotic aryl hydrocarbon receptor, as well as target genes of the Wnt signaling pathway, which is mediated by the lymphocyte enhancer factor (LEF)/T cell factor transcription factors and the coactivator β-catenin. The recruitment of CoCoA by nuclear receptors is accomplished by the interaction of the central coiled-coiled domain of CoCoA with p160 coactivators; the C-t...

  11. Lack of Csk-mediated negative regulation in a unicellular SRC kinase.

    Science.gov (United States)

    Schultheiss, Kira P; Suga, Hiroshi; Ruiz-Trillo, Iñaki; Miller, W Todd

    2012-10-16

    Phosphotyrosine-based signaling plays a vital role in cellular communication in multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest phylogenetic group to metazoans) possess numbers of tyrosine kinases that are comparable to those in complex metazoans. Here, we have characterized tyrosine kinases from the filasterean Capsaspora owczarzaki, a unicellular protist representing the sister group to choanoflagellates and metazoans. Two Src-like tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both of which have the arrangement of SH3, SH2, and catalytic domains seen in mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to punctate structures in filopodia that may represent primordial focal adhesions. We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are active tyrosine kinases. Mammalian Src kinases are normally regulated in a reciprocal fashion by autophosphorylation in the activation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (which inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We cloned, expressed, and purified CoCsk and found that it has no measurable tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src family kinases appears to have arisen with the emergence of metazoans.

  12. Central functions of bicarbonate in S-type anion channel activation and OST1 protein kinase in CO 2 signal transduction in guard cell

    KAUST Repository

    Xue, Shaowu; Hu, Honghong; Ries, Amber; Merilo, Ebe; Kollist, Hannes; Schroeder, Julian I

    2011-01-01

    Plants respond to elevated CO(2) via carbonic anhydrases that mediate stomatal closing, but little is known about the early signalling mechanisms following the initial CO(2) response. It remains unclear whether CO(2), HCO(3)(-) or a combination activates downstream signalling. Here, we demonstrate that bicarbonate functions as a small-molecule activator of SLAC1 anion channels in guard cells. Elevated intracellular [HCO(3)(-)](i) with low [CO(2)] and [H(+)] activated S-type anion currents, whereas low [HCO(3)(-)](i) at high [CO(2)] and [H(+)] did not. Bicarbonate enhanced the intracellular Ca(2+) sensitivity of S-type anion channel activation in wild-type and ht1-2 kinase mutant guard cells. ht1-2 mutant guard cells exhibited enhanced bicarbonate sensitivity of S-type anion channel activation. The OST1 protein kinase has been reported not to affect CO(2) signalling. Unexpectedly, OST1 loss-of-function alleles showed strongly impaired CO(2)-induced stomatal closing and HCO(3)(-) activation of anion channels. Moreover, PYR/RCAR abscisic acid (ABA) receptor mutants slowed but did not abolish CO(2)/HCO(3)(-) signalling, redefining the convergence point of CO(2) and ABA signalling. A new working model of the sequence of CO(2) signalling events in gas exchange regulation is presented.

  13. Central functions of bicarbonate in S-type anion channel activation and OST1 protein kinase in CO 2 signal transduction in guard cell

    KAUST Repository

    Xue, Shaowu

    2011-03-18

    Plants respond to elevated CO(2) via carbonic anhydrases that mediate stomatal closing, but little is known about the early signalling mechanisms following the initial CO(2) response. It remains unclear whether CO(2), HCO(3)(-) or a combination activates downstream signalling. Here, we demonstrate that bicarbonate functions as a small-molecule activator of SLAC1 anion channels in guard cells. Elevated intracellular [HCO(3)(-)](i) with low [CO(2)] and [H(+)] activated S-type anion currents, whereas low [HCO(3)(-)](i) at high [CO(2)] and [H(+)] did not. Bicarbonate enhanced the intracellular Ca(2+) sensitivity of S-type anion channel activation in wild-type and ht1-2 kinase mutant guard cells. ht1-2 mutant guard cells exhibited enhanced bicarbonate sensitivity of S-type anion channel activation. The OST1 protein kinase has been reported not to affect CO(2) signalling. Unexpectedly, OST1 loss-of-function alleles showed strongly impaired CO(2)-induced stomatal closing and HCO(3)(-) activation of anion channels. Moreover, PYR/RCAR abscisic acid (ABA) receptor mutants slowed but did not abolish CO(2)/HCO(3)(-) signalling, redefining the convergence point of CO(2) and ABA signalling. A new working model of the sequence of CO(2) signalling events in gas exchange regulation is presented.

  14. Incentive-based regulation of CO2 emissions from international aviation

    International Nuclear Information System (INIS)

    Carlsson, F.; Hammar, H.

    2002-01-01

    We explore the possibilities of using incentive-based environmental regulations of CO 2 emissions from international civil aviation. In theory incentive-based instruments such as an emission charge or a tradable emission permit system are better regulations than so-called command-and-control regulations such as emission limits or technology standards. However, the implementation of these instruments is a complex issue. We therefore describe and discuss how an emission charge and a tradable emission permit system for international aviation should be designed in order to improve efficiency. We also compare these two types of regulations. In brief, we find that an emission charge and a tradable emission permit system in which the permits are auctioned have more or less the same characteristics. The main advantage of a tradable emission permit system is that the effect, in terms of emission reductions, is known. On the other hand, we show that under uncertainty an emission charge is preferred. The choice of regulation is a political decision and it does not seem likely that an environmental charge or a tradable emission permit system would be implemented without consideration of the costs of the regulation. Revenue-neutral charges or gratis distribution of permits would, for this reason, be realistic choices of regulations. However, such actions are likely to result in less stringent regulations and other negative welfare effects.(author)

  15. Co-activation: its association with weakness and specific neurological pathology

    Directory of Open Access Journals (Sweden)

    Wiles Charles M

    2006-11-01

    Full Text Available Abstract Background Net agonist muscle strength is in part determined by the degree of antagonist co-activation. The level of co-activation might vary in different neurological disorders causing weakness or might vary with agonist strength. Aim This study investigated whether antagonist co-activation changed a with the degree of muscle weakness and b with the nature of the neurological lesion causing weakness. Methods Measures of isometric quadriceps and hamstrings strength were obtained. Antagonist (hamstring co-activation during knee extension was calculated as a ratio of hamstrings over quadriceps activity both during an isometric and during a functional sit to stand (STS task (using kinematics in groups of patients with extrapyramidal (n = 15, upper motor neuron (UMN (n = 12, lower motor neuron (LMN with (n = 18 or without (n = 12 sensory loss, primary muscle or neuromuscular junction disorder (n = 17 and in healthy matched controls (n = 32. Independent t-tests or Mann Witney U tests were used to compare between the groups. Correlations between variables were also investigated. Results In healthy subjects mean (SD co-activation of hamstrings during isometric knee extension was 11.8 (6.2% and during STS was 20.5 (12.9%. In patients, co-activation ranged from 7 to 17% during isometric knee extension and 15 to 25% during STS. Only the extrapyramidal group had lower co-activation levels than healthy matched controls (p Conclusion It is concluded that antagonist co-activation does not systematically vary with the site of neurological pathology when compared to healthy matched controls or, in most patient groups, with strength. The lower co-activation levels found in the extrapyramidal group require confirmation and further investigation. Co-activation may be relevant to individuals with muscle weakness. Within patient serial studies in the presence of changing muscle strength may help to understand these relationships more clearly.

  16. Inhibition of Ku70 acetylation by INHAT subunit SET/TAF-Iβ regulates Ku70-mediated DNA damage response.

    Science.gov (United States)

    Kim, Kee-Beom; Kim, Dong-Wook; Park, Jin Woo; Jeon, Young-Joo; Kim, Daehwan; Rhee, Sangmyung; Chae, Jung-Il; Seo, Sang-Beom

    2014-07-01

    DNA double-strand breaks (DSBs) can cause either cell death or genomic instability. The Ku heterodimer Ku70/80 is required for the NHEJ (non-homologous end-joining) DNA DSB repair pathway. The INHAT (inhibitor of histone acetyltransferases) complex subunit, SET/TAF-Iβ, can inhibit p300- and PCAF-mediated acetylation of both histone and p53, thereby repressing general transcription and that of p53 target genes. Here, we show that SET/TAF-Iβ interacts with Ku70/80, and that this interaction inhibits CBP- and PCAF-mediated Ku70 acetylation in an INHAT domain-dependent manner. Notably, DNA damage by UV disrupted the interaction between SET/TAF-Iβ and Ku70. Furthermore, we demonstrate that overexpressed SET/TAF-Iβ inhibits recruitment of Ku70/80 to DNA damage sites. We propose that dysregulation of SET/TAF-Iβ expression prevents repair of damaged DNA and also contributes to cellular proliferation. All together, our findings indicate that SET/TAF-Iβ interacts with Ku70/80 in the nucleus and inhibits Ku70 acetylation. Upon DNA damage, SET/TAF-Iβ dissociates from the Ku complex and releases Ku70/Ku80, which are then recruited to DNA DSB sites via the NHEJ DNA repair pathway.

  17. Modern aspects of tax regulation of investment activity

    Directory of Open Access Journals (Sweden)

    E.S. Podakov

    2016-03-01

    Full Text Available The article investigates the tax regulation of investment activity in modern conditions. Scientists studied different views about the impact of tax regulations on the investment activity in the country. The author determines that the tax regulation of investment activity involves the use of state mechanisms taxation of certain measures to improve investment conditions. The subject is the state tax regulations, and the object is the investment activity of individual and institutional investors of any form of ownership including organizational and legal forms. Such regulation is performed by using complex special tools. The possible methods of tax stimulation of investment processes are described. The article deals with the current results of tax reform in Ukraine and predicts its possible consequences for agricultural producers. The rating positions of Ukraine according to international organizations are showed. The systematic analysis has been carried out and the impact of differential tax rates, tax exemption for a specified period, reducing the tax base, elimination of double taxation on investment activity in certain areas have been researched. The special instruments of investment activity tax regulation are considered. The options for improving investment activity by introducing effective tax regulation are determined.

  18. Two modes of regulation of the fatty acid elongase ELOVL6 by the 3-ketoacyl-CoA reductase KAR in the fatty acid elongation cycle.

    Directory of Open Access Journals (Sweden)

    Tatsuro Naganuma

    Full Text Available Fatty acids (FAs are diverse molecules, and such diversity is important for lipids to exert their functions under several environmental conditions. FA elongation occurs at the endoplasmic reticulum and produces a variety of FA species; the FA elongation cycle consists of four distinct enzyme reactions. For this cycle to be driven efficiently, there must exist coordinated regulation of protein components of the FA elongation machinery. However, such regulation is poorly understood. In the present study, we performed biochemical analyses using the FA elongase ELOVL6 and the 3-ketoacyl-CoA reductase KAR, which catalyze the first and second steps of the FA elongation cycle, respectively. In vitro FA elongation assays using membrane fractions demonstrated that ELOVL6 activity was enhanced ∼10-fold in the presence of NADPH, although ELOVL6 itself did not require NADPH for its catalysis. On the other hand, KAR does use NADPH as a reductant in its enzyme reaction. Activity of purified ELOVL6 was enhanced by ∼3-fold in the presence of KAR. This effect was KAR enzyme activity-independent, since it was observed in the absence of NADPH and in the KAR mutant. However, ELOVL6 enzyme activity was further enhanced in a KAR enzyme activity-dependent manner. Therefore, KAR regulates ELOVL6 via two modes. In the first mode, KAR may induce conformational changes in ELOVL6 to become structure that can undergo catalysis. In the second mode, conversion of 3-ketoacyl-CoA to 3-hydroxyacyl-CoA by KAR may facilitate release of the product from the presumed ELOVL6-KAR complex.

  19. Regulation by carbohydrate and clofibric acid of palmitoyl-CoA chain elongation in the liver of rats.

    Science.gov (United States)

    Kudo, Naomi; Toyama, Tomoaki; Mitsumoto, Atsushi; Kawashima, Yoichi

    2003-05-01

    Regulation of palmitoyl-CoA chain elongation (PCE) and its contribution to oleic acid formation were investigated in rat liver in comparison with stearoyl-CoA desaturase (SCD). Hepatic PCE activity was induced by the administration of 20% wt/vol glucose or fructose in the drinking water of normal rats. In streptozotocin-induced diabetic rats, the activities of both PCE and SCD were suppressed, and fructose, but not glucose, feeding caused an increase in the activities of both enzymes. Treatment of normal rats with clofibric acid in combination with carbohydrate further increased PCE, but not SCD, activity. FA analysis of hepatic lipids revealed that the proportion of oleic acid (18:1 n-9) increased upon administration of carbohydrate or clofibric acid. The treatment of rats with clofibric acid in combination with carbohydrate greatly increased the proportion of 18:1 n-9. A significant correlation was observed between PCE activity and the hepatic proportion of 18:1 n-9 (r2 = 0.874, P 0.05). Taken together, these results suggest that carbohydrate induces PCE as well as SCD activity to increase the hepatic 18:1 content in rat liver, and the increased PCE activity seems to be responsible for the further increase in 18:1 n-9 when carbohydrate is administered in combination with clofibric acid.

  20. Regulation of p21ras activity

    DEFF Research Database (Denmark)

    Lowy, D R; Zhang, K; DeClue, J E

    1992-01-01

    The ras genes encode GTP/GDP-binding proteins that participate in mediating mitogenic signals from membrane tyrosine kinases to downstream targets. The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative control...... mechanisms. GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Other cellular factors can positively regulate p21ras by stimulating GDP/GTP exchange....

  1. Regulation of ROCK Activity in Cancer

    Science.gov (United States)

    Morgan-Fisher, Marie; Wewer, Ulla M.

    2013-01-01

    Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

  2. Student profiling on university co-curricular activities using cluster analysis

    Science.gov (United States)

    Rajenthran, Hemabegai A./P.; Shaharanee, Izwan Nizal Mohd; Jamil, Jastini Mohd.

    2017-11-01

    In higher learning institutions, the co-curricular programs are needed for the graduation besides the standard academic programs. By actively participating in co-curricular, students can attain many of soft skills and proficiencies besides learning and adopting campus environment, community and traditions. Co-curricular activities are implemented by universities mainly for the refinement of the academic achievement along with the social development. This studies aimed to analyse the academic profile of the co-curricular students among uniform units. The main objective of study is to develop a profile of student co-curricular activities in uniform units. Additionally, several variables has been selected to serve as the characteristics for student co-curricular profile. The findings of this study demonstrate the practicality of clustering technique to investigate student's profiles and allow for a better understanding of student's behavior and co-curriculum activities.

  3. Blowing loop in the EL-4 reactor: CO{sub 2} flow control analogue study; Boucle de soufflage de la centrale EL-4 - regulation du debit CO{sub 2} - etude analogique

    Energy Technology Data Exchange (ETDEWEB)

    Chazal, G; Merle, J P; Guillemard, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Leroy, C; Robin, L; Jacquin, J C; Cornudet, A [Societe INDATOM, France (France)

    1966-07-01

    This report describes one study which contributed to the construction of the Monts d'Arree nuclear power station: EL-4. The reactor is cooled by a CO{sub 2} current provided by 3 turbo-blower groups. The priming vapour for the turbines is taken at the exit of the main CO{sub 2} - H{sub 2}O exchangers. The operation of EL 4 is based on a high degree of centralization of the controls which attributes an important role to the general regulation circuits. This general regulation includes in particular an internal blowing loop which controls the CO{sub 2} flow. The study of the control of this CO{sub 2} flow is made up of 3 parts: - analogue representation of the reactors cooling circuit and of the turbo blower unit. - first test campaign using the analogue computer describing the natural behaviour of the system in the absence of control. theoretical determination of the regulation factors; definition of the regulation using an analogue computer and second test campaign for recording the performances of the blowing loop. The 4. part of the report deals with the analogue study: analogue equations - development. (authors) [French] Ce rapport prend place parmi les etudes de realisation de la Centrale des Monts d'Arree EL-4. Le reacteur est refroidi par une circulation de CO{sub 2} assuree par 3 groupes turbosoufflantes. La vapeur d'entrainement des turbines est prelevee a la sortie des echangeurs principaux CO{sub 2} - H{sub 2}O. L'exploitation de EL-4 repose sur une centralisation poussee des moyens de controle-commande qui attribue un role essentiel aux circuits de regulation generale. Cette regulation generale comporte en particulier une boucle interne de soufflage qui realise un asservissement du debit de CO{sub 2}. L'etude de cette regulation du debit CO{sub 2} comprend 3 parties: - representation analogique du circuit de refroidissement du reacteur et de l'ensemble turbine-soufflante. - premiere campagne d'essais sur calculateur analogique decrivant le comportement

  4. Expert Voices in Learning Improvisation: Shaping Regulation Processes through Experiential Influence

    Science.gov (United States)

    de Bruin, Leon R.

    2017-01-01

    Interpersonal and collaborative activity plays an important role in the social aspects of self-regulated learning (SRL) development. Peer, teacher and group interactions facilitate support for self-regulation, co-regulation and socially shared regulatory processes. Situated and experiential interplay facilitates personal, co-constructed and…

  5. Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

    2014-10-02

    Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

  6. Integration of the tricarboxylic acid (TCA) cycle with cAMP signaling and Sfl2 pathways in the regulation of CO2 sensing and hyphal development in Candida albicans.

    Science.gov (United States)

    Tao, Li; Zhang, Yulong; Fan, Shuru; Nobile, Clarissa J; Guan, Guobo; Huang, Guanghua

    2017-08-01

    Morphological transitions and metabolic regulation are critical for the human fungal pathogen Candida albicans to adapt to the changing host environment. In this study, we generated a library of central metabolic pathway mutants in the tricarboxylic acid (TCA) cycle, and investigated the functional consequences of these gene deletions on C. albicans biology. Inactivation of the TCA cycle impairs the ability of C. albicans to utilize non-fermentable carbon sources and dramatically attenuates cell growth rates under several culture conditions. By integrating the Ras1-cAMP signaling pathway and the heat shock factor-type transcription regulator Sfl2, we found that the TCA cycle plays fundamental roles in the regulation of CO2 sensing and hyphal development. The TCA cycle and cAMP signaling pathways coordinately regulate hyphal growth through the molecular linkers ATP and CO2. Inactivation of the TCA cycle leads to lowered intracellular ATP and cAMP levels and thus affects the activation of the Ras1-regulated cAMP signaling pathway. In turn, the Ras1-cAMP signaling pathway controls the TCA cycle through both Efg1- and Sfl2-mediated transcriptional regulation in response to elevated CO2 levels. The protein kinase A (PKA) catalytic subunit Tpk1, but not Tpk2, may play a major role in this regulation. Sfl2 specifically binds to several TCA cycle and hypha-associated genes under high CO2 conditions. Global transcriptional profiling experiments indicate that Sfl2 is indeed required for the gene expression changes occurring in response to these elevated CO2 levels. Our study reveals the regulatory role of the TCA cycle in CO2 sensing and hyphal development and establishes a novel link between the TCA cycle and Ras1-cAMP signaling pathways.

  7. Integration of the tricarboxylic acid (TCA cycle with cAMP signaling and Sfl2 pathways in the regulation of CO2 sensing and hyphal development in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Li Tao

    2017-08-01

    Full Text Available Morphological transitions and metabolic regulation are critical for the human fungal pathogen Candida albicans to adapt to the changing host environment. In this study, we generated a library of central metabolic pathway mutants in the tricarboxylic acid (TCA cycle, and investigated the functional consequences of these gene deletions on C. albicans biology. Inactivation of the TCA cycle impairs the ability of C. albicans to utilize non-fermentable carbon sources and dramatically attenuates cell growth rates under several culture conditions. By integrating the Ras1-cAMP signaling pathway and the heat shock factor-type transcription regulator Sfl2, we found that the TCA cycle plays fundamental roles in the regulation of CO2 sensing and hyphal development. The TCA cycle and cAMP signaling pathways coordinately regulate hyphal growth through the molecular linkers ATP and CO2. Inactivation of the TCA cycle leads to lowered intracellular ATP and cAMP levels and thus affects the activation of the Ras1-regulated cAMP signaling pathway. In turn, the Ras1-cAMP signaling pathway controls the TCA cycle through both Efg1- and Sfl2-mediated transcriptional regulation in response to elevated CO2 levels. The protein kinase A (PKA catalytic subunit Tpk1, but not Tpk2, may play a major role in this regulation. Sfl2 specifically binds to several TCA cycle and hypha-associated genes under high CO2 conditions. Global transcriptional profiling experiments indicate that Sfl2 is indeed required for the gene expression changes occurring in response to these elevated CO2 levels. Our study reveals the regulatory role of the TCA cycle in CO2 sensing and hyphal development and establishes a novel link between the TCA cycle and Ras1-cAMP signaling pathways.

  8. CD28 co-stimulation down regulates Th17 development.

    Directory of Open Access Journals (Sweden)

    Salim Bouguermouh

    Full Text Available Th17 cells are implicated in host defence and autoimmune diseases. CD28/B7 co-stimulation is involved in the induction and progression of autoimmune diseases, but its role in controlling murine Th17 cell fate remains to be clarified. We here report that soluble anti-CD28 mAb suppressed the differentiation of anti-CD3-stimulated naïve CD4(+ T cells into IL-17-producing cells. CD28 co-stimulation reduced the frequency of proliferating cells that produce IL-17. We provide evidence for an IL-2 and IFN-gamma-dependent mechanism of CD28-mediated IL-17 suppression. CD28 blockade of Th17 development was correlated with a decrease rather than an increase in the percentage of Foxp3(+ T cells. In APC/T cell co-cultures, mature dendritic cells (DC were less efficient than immature DC in their ability to support Th17 cell differentiation, while CTLA4-Ig, an agent blocking CD28/B7 and CTLA4/B7 interactions, facilitated both murine and human Th17 differentiation. This study identifies the importance of B7 co-stimulatory molecules in the negative regulation of Th17 development. These unexpected results caution targeting the CD28/B7 pathways in the treatment of human autoimmune diseases.

  9. ITER co-ordinated technical activities

    International Nuclear Information System (INIS)

    2001-01-01

    As agreed upon between the ITER Engineering Design Activities (EDA) Parties 'Co-ordinated Technical Activities' (CTA) means technical activities which are deemed necessary to maintain the integrity of the international project, so as to prepare for the ITER joint implementation. The scope of these activities includes design adaptation to the specific site conditions, safety analysis and licensing preparation that are based on specific site offers, evaluation of cost and construction schedule, preparation of procurement documents and other issues raised by the Parties collectively, whilst assuring the coherence of the ITER project including design control

  10. Soil and water warming accelerates phenology and down-regulation of leaf photosynthesis of rice plants grown under free-air CO2 enrichment (FACE).

    Science.gov (United States)

    Adachi, Minaco; Hasegawa, Toshihiro; Fukayama, Hiroshi; Tokida, Takeshi; Sakai, Hidemitsu; Matsunami, Toshinori; Nakamura, Hirofumi; Sameshima, Ryoji; Okada, Masumi

    2014-02-01

    To enable prediction of future rice production in a changing climate, we need to understand the interactive effects of temperature and elevated [CO2] (E[CO2]). We therefore examined if the effect of E[CO2] on the light-saturated leaf photosynthetic rate (Asat) was affected by soil and water temperature (NT, normal; ET, elevated) under open-field conditions at the rice free-air CO2 enrichment (FACE) facility in Shizukuishi, Japan, in 2007 and 2008. Season-long E[CO2] (+200 µmol mol(-1)) increased Asat by 26%, when averaged over two years, temperature regimes and growth stages. The effect of ET (+2°C) on Asat was not significant at active tillering and heading, but became negative and significant at mid-grain filling; Asat in E[CO2]-ET was higher than in ambient [CO2] (A[CO2])-NT by only 4%. Photosynthetic down-regulation at E[CO2] also became apparent at mid-grain filling; Asat compared at the same [CO2] in the leaf cuvette was significantly lower in plants grown in E[CO2] than in those grown in A[CO2]. The additive effects of E[CO2] and ET decreased Asat by 23% compared with that of A[CO2]-NT plants. Although total crop nitrogen (N) uptake was increased by ET, N allocation to the leaves and to Rubisco was reduced under ET and E[CO2] at mid-grain filling, which resulted in a significant decrease (32%) in the maximum rate of ribulose-1,5-bisphosphate carboxylation on a leaf area basis. Because the change in N allocation was associated with the accelerated phenology in E[CO2]-ET plants, we conclude that soil and water warming accelerates photosynthetic down-regulation at E[CO2].

  11. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    International Nuclear Information System (INIS)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun; Nishina, Hiroshi

    2014-01-01

    Highlights: •Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. •The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. •Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription

  12. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    Energy Technology Data Exchange (ETDEWEB)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun, E-mail: hirayama.dbio@mri.tmd.ac.jp; Nishina, Hiroshi, E-mail: nishina.dbio@mri.tmd.ac.jp

    2014-01-17

    Highlights: •Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. •The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. •Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.

  13. Dual roles for CoAA and its counterbalancing isoform CoAM in human kidney cell tumorigenesis

    Science.gov (United States)

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y.; Tsai, Ming-Jer; W. O’Malley, Bert

    2008-01-01

    Co-Activator Activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein we show that CoAA is a dual-function coregulator that inhibits G1/S transition in human kidney cells and suppresses anchorage independent growth and xenograft tumor formation. Suppression occurs in part by downregulating c-myc and its downstream effectors ccnd1 and skp2, and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene, c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, Coactivator Modulator (CoAM), antagonizes CoAA-induced G1/S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma as compared to normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice-isoform. This is so far the only example of a nuclear receptor coregulator involved in suppression of kidney cancer, and suggests potentially significant new roles for coregulators in renal cancer biology. PMID:18829545

  14. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    Science.gov (United States)

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Three-dimensional collagen I promotes gemcitabine resistance in vitro in pancreatic cancer cells through HMGA2-dependent histone acetyltransferase expression.

    Directory of Open Access Journals (Sweden)

    Surabhi Dangi-Garimella

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells are resistant to gemcitabine chemotherapy in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2. We have now found that human PDAC tumors display higher levels of histone H3K9 and H3K27 acetylation in fibrotic regions. We show that relative to cells grown on tissue culture plastic, PDAC cells grown in three-dimensional collagen gels demonstrate increased histone H3K9 and H3K27 acetylation, along with increased expression of p300, PCAF and GCN5 histone acetyltransferases (HATs. Knocking down HMGA2 attenuates the effect of collagen on histone H3K9 and H3K27 acetylation and on collagen-induced p300, PCAF and GCN5 expression. We also show that human PDAC tumors with HMGA2 demonstrate increased histone H3K9 and H3K27 acetylation. Additionally, we show that cells in three-dimensional collagen gels demonstrate increased protection against gemcitabine. Significantly, down-regulation of HMGA2 or p300, PCAF and GCN5 HATs sensitizes the cells to gemcitabine in three-dimensional collagen. Overall, our results increase our understanding of how the collagen microenvironment contributes to chemo-resistance in vitro and identify HATs as potential therapeutic targets against this deadly cancer.

  16. Large-scale analysis of Arabidopsis transcription reveals a basal co-regulation network

    Directory of Open Access Journals (Sweden)

    Chamovitz Daniel A

    2009-09-01

    Full Text Available Abstract Background Analyses of gene expression data from microarray experiments has become a central tool for identifying co-regulated, functional gene modules. A crucial aspect of such analysis is the integration of data from different experiments and different laboratories. How to weigh the contribution of different experiments is an important point influencing the final outcomes. We have developed a novel method for this integration, and applied it to genome-wide data from multiple Arabidopsis microarray experiments performed under a variety of experimental conditions. The goal of this study is to identify functional globally co-regulated gene modules in the Arabidopsis genome. Results Following the analysis of 21,000 Arabidopsis genes in 43 datasets and about 2 × 108 gene pairs, we identified a globally co-expressed gene network. We found clusters of globally co-expressed Arabidopsis genes that are enriched for known Gene Ontology annotations. Two types of modules were identified in the regulatory network that differed in their sensitivity to the node-scoring parameter; we further showed these two pertain to general and specialized modules. Some of these modules were further investigated using the Genevestigator compendium of microarray experiments. Analyses of smaller subsets of data lead to the identification of condition-specific modules. Conclusion Our method for identification of gene clusters allows the integration of diverse microarray experiments from many sources. The analysis reveals that part of the Arabidopsis transcriptome is globally co-expressed, and can be further divided into known as well as novel functional gene modules. Our methodology is general enough to apply to any set of microarray experiments, using any scoring function.

  17. Effective Peroxidase-Like Activity of Co-Aminoclay [CoAC] and Its Application for Glucose Detection

    Directory of Open Access Journals (Sweden)

    Han Pill Song

    2018-02-01

    Full Text Available In this study, we describe a novel peroxidase-like activity of Co-aminoclay [CoAC] present at pH ~5.0 and its application to fluorescent biosensor for the determination of H2O2 and glucose. It is synthesized with aminoclays (ACs entrapping cationic metals such as Fe, Cu, Al, Co., Ce, Ni, Mn, and Zn to find enzyme mimicking ACs by sol–gel ambient conditions. Through the screening of catalytic activities by the typical colorimetric reaction employing 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic aciddiammonium salt (ABTS as a substrate with or without H2O2, Fe, Cu, and CoACs are found to exhibit peroxidase-like activity, as well as oxidase-like activity was observed from Ce and MnACs. Among them, CoAC shows exceptionally high peroxidase-like activity, presumably due to its ability to induce electron transfer between substrates and H2O2. CoAC is then used to catalyze the oxidation of Amplex® UltraRed (AUR into a fluorescent end product, which enables a sensitive fluorescent detection of H2O2. Moreover, a highly sensitive and selective glucose biosensing strategy is developed, based on enzyme cascade reaction between glucose oxidase (GOx and CoAC. Using this strategy, a highly linear fluorescence enhancement is verified when the concentration of glucose is increased in a wide range from 10 μM to 1 mM with a lower detection limit of 5 μM. The practical diagnostic capability of the assay system is also verified by its use to detect glucose in human blood serum. Based on these results, it is anticipated that CoAC can serve as potent peroxidase mimetics for the detection of clinically important target molecules.

  18. Crystal structure of B acillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity: AtxA multimerization, phosphorylation and activity

    Energy Technology Data Exchange (ETDEWEB)

    Hammerstrom, Troy G.; Lori, Horton B.; Swick, Michelle C.; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M.

    2014-12-30

    The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (HisAsp) and phosphoablative (HisAla) amino acid changes for activity in B.anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.

  19. Interfacial-Bonding-Regulated CO Oxidation over Pt Atoms Immobilized on Gas-Exfoliated Hexagonal Boron Nitride

    KAUST Repository

    Liu, Xin

    2017-10-12

    We compared the electronic structure and CO oxidation mechanisms over Pt atoms immobilized by both B-vacancies and N-vacancies on gas-exfoliated hexagonal boron nitride. We showed that chemical bonds are formed between the B atoms associated with dangling bonds around the vacancies and Pt atoms. These bonds not only alter the thermodynamics and kinetics for the aggregation and effectively immobilize Pt atoms, but also significantly change the composition and energetic distribution of the electronic states of the composites to circumvent CO poisoning and to favour coadsorption of CO and O2, which further regulates the reactions to proceed through a Langmuir-Hinshelwood mechanism. The CO oxidation over Pt atoms immobilized at N-vacancies involves formation of an intermediate with –C(O)-O−O- bonded to Pt, the generation of CO2 by peroxo O−O bond scission and the reduction of the remnant oxygen, and the calculated energy barriers are 0.49, 0.23 and 0.18 eV, respectively. Such small energy barriers are comparable to those over Pt atoms trapped at B-vacancies, showing the effectiveness of Pt/hexagonal boron nitride atomic composites as catalysts for CO oxidation. These findings also suggest the feasibility of regulating the reaction pathways over single atom catalysts via interfacial engineering.

  20. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

  1. Enhanced down regulation of cortical ±-propranolol sensitive [3H]-DHA binding sites by co-administration of DMI and 5-HT1A partial agonist gepirone

    International Nuclear Information System (INIS)

    Geissler, M.A.; Yocca, F.D.

    1990-01-01

    The putative interrelationship between the noradrenergic and serotonergic systems has been supported by numerous studies. Recently, Dudley et al. (1989) demonstrated significant down regulation of cortical β-adrenergic receptors by co-administration of desipramine (DMI), a norepinephrine uptake inhibitor, and the full 5-HT 1A agonist 8-OH-DPAT. To this end, the effects of acute and chronic (4 and 14 day) administration of DMI, gepirone, a selective 5-HT 1A post-synaptic partial agonist, as well as a combination of the two, on cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites were examined in rats. Down regulation was apparent after 4 and 14 day treatment with DMI. However, this was not the case with gepirone. Of particular importance is the demonstration of a greater magnitude of down regulation with co-administration of a greater magnitude of down regulation with co-administration of DMI and gepirone. These results suggests that alteration in rat cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites by noradrenergic uptake inhibitors can be further modulated by selective partial agonist activity at central 5-HT 1A postsynaptic receptors. Further data on the co-administration of DMI and BMY 7378 (7,9-dioxo-8-[2-(4-o-methoxyphenylpiperazinyl)ethyl]-8-azaspiro[4,5]decane dihydrochloride), a weak partial agonist at postsynaptic 5-HT 1A receptors, are also presented

  2. Acyl-CoA metabolism and partitioning

    DEFF Research Database (Denmark)

    Grevengoed, Trisha J; Klett, Eric L; Coleman, Rosalind A

    2014-01-01

    Long-chain fatty acyl-coenzyme As (CoAs) are critical regulatory molecules and metabolic intermediates. The initial step in their synthesis is the activation of fatty acids by one of 13 long-chain acyl-CoA synthetase isoforms. These isoforms are regulated independently and have different tissue...

  3. Interactive effects of hypoxia and PCB co-exposure on expression of CYP1A and its potential regulators in Atlantic croaker liver.

    Science.gov (United States)

    Rahman, Md Saydur; Thomas, Peter

    2018-04-01

    Although marine and coastal environments which are contaminated with xenobiotic organic compounds often become hypoxic during the summer, the interactive effects of hypoxia and xenobiotic exposure on marine species such as teleost fishes remain poorly understood. The expression and activity of monooxygenase enzyme cytochrome P450-1A (CYP1A) in fishes are upregulated by exposure to polychlorinated biphenyls (PCBs), whereas they are down-regulated during hypoxia exposure. We investigated the interactive effects of hypoxia and PCB co-exposure on hepatic CYP1A expression in Atlantic croaker and on potential regulators of CYP1A. Croaker were exposed to hypoxia (1.7 mg/L dissolved oxygen), 3,3',4,4'-tetrachlorobiphenyl (PCB 77, dose: 2 and 8 µg/g body weight), and Aroclor 1254 (a common PCB mixture, dose: 0.5 and 1 µg/g body weight), alone and in combination for 4 weeks. PCB 77 exposure markedly increased hepatic CYP1A mRNA and protein expression, and ethoxyresorufin-O-deethylase (EROD, an indicator of CYP1A enzyme) activity and increased endothelial nitric oxide synthase (eNOS) protein expression. PCB 77 treatment also increased interleukin-1β (IL-1β, a cytokine) mRNA levels and protein carbonyl (PC, an indicator of reactive oxygen species, ROS) contents. These marked PCB 77- and Aroclor 1254-induced increases in CYP1A mRNA levels and EROD activity were significantly attenuated by co-exposure to hypoxia, whereas the increases in hepatic eNOS protein and IL-1β mRNA expression, and PC contents were augmented by hypoxia co-exposure. The results suggest that biotransformation of organic xenobiotics by CYP1A is reduced in fish during co-exposure to hypoxia and is accompanied by alterations in eNOS, ROS, and IL-1β levels. © 2018 Wiley Periodicals, Inc.

  4. Regulation of higher-activity NARM wastes by EPA

    International Nuclear Information System (INIS)

    Bandrowski, M.S.

    1988-01-01

    The US Environmental Protection Agency (EPA) is currently developing standards for the disposal of low-level radioactive waste (LLW). As part of this Standard, EPA is including regulations for the disposal of naturally occurring and accelerator-produced radioactive material (NARM) wastes not covered under the Atomic Energy Act (AEA). The regulations will cover only higher-activity NARM wastes, defined as NARM waste with specific activity exceeding two nanocuries per gram. The proposed regulations will specify that NARM wastes exceeding the above limits, except for specific exempted items, must be disposed of in regulated radioactive waste disposal facilities. The proposed EPA regulations for NARM wastes will be discussed, as well as the costs and benefits of the regulation, how it will be implemented by EPA, and the rationale for covering only higher-activity NARM wastes exceeding two nanocuries per gram

  5. DAX1 suppresses FXR transactivity as a novel co-repressor

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); Ning, Guang, E-mail: guangning@gmail.com.cn [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); The Key Laboratory of Endocrine Tumors and The Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025 (China); Li, Xiaoying, E-mail: lixy@sibs.ac.cn [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); The Key Laboratory of Endocrine Tumors and The Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025 (China)

    2011-09-09

    Highlights: {yields} DAX1 is co-localized with FXR and interacts with FXR. {yields} DAX1 acts as a negative regulator of FXR. {yields} Three LXXLL motifs in the N-terminus of DAX1 were required. {yields} DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1{alpha}. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

  6. DAX1 suppresses FXR transactivity as a novel co-repressor

    International Nuclear Information System (INIS)

    Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng; Ning, Guang; Li, Xiaoying

    2011-01-01

    Highlights: → DAX1 is co-localized with FXR and interacts with FXR. → DAX1 acts as a negative regulator of FXR. → Three LXXLL motifs in the N-terminus of DAX1 were required. → DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1α. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

  7. Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-{gamma}2

    Energy Technology Data Exchange (ETDEWEB)

    Mitterberger, Maria C. [Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, 6020 Innsbruck (Austria); Kim, Geumsoo [Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012 (United States); Rostek, Ursula [Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, 6020 Innsbruck (Austria); Levine, Rodney L. [Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012 (United States); Zwerschke, Werner, E-mail: werner.zwerschke@oeaw.ac.at [Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, 6020 Innsbruck (Austria)

    2012-05-01

    Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO{sub 2} have been proposed. CAIII expression is highly induced in adipogenesis and CAIII is the most abundant protein in adipose tissues. The function of CAIII in both preadipocytes and adipocytes is however unknown. In the present study we demonstrate that adipogenesis is greatly increased in mouse embryonic fibroblasts (MEFs) from CAIII knockout (KO) mice, as demonstrated by a greater than 10-fold increase in the induction of fatty acid-binding protein-4 (FABP4) and increased triglyceride formation in CAIII{sup -/-} MEFs compared with CAIII{sup +/+} cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-{gamma}2 (PPAR{gamma}2) and CCAAT/enhancer binding protein-{alpha}. We found a considerable (approximately 1000-fold) increase in the PPAR{gamma}2 expression in the CAIII{sup -/-} MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPAR{gamma}2 and FABP4. When both CAIII and PPAR{gamma}2 were knocked down, FABP4 was not induced. We conclude that down-regulation of CAIII in preadipocytes enhances adipogenesis and that CAIII is a regulator of adipogenic differentiation which acts at the level of PPAR{gamma}2 gene expression. -- Highlights: Black-Right-Pointing-Pointer We discover a novel function of Carbonic anhydrase III (CAIII). Black-Right-Pointing-Pointer We show that CAIII is a regulator of adipogenesis. Black-Right-Pointing-Pointer We demonstrate that CAIII acts at the level of PPAR{gamma}2 gene expression. Black-Right-Pointing-Pointer Our data contribute to a better understanding of the role of CAIII in fat tissue.

  8. cGMP and NHR signaling co-regulate expression of insulin-like peptides and developmental activation of infective larvae in Strongyloides stercoralis.

    Directory of Open Access Journals (Sweden)

    Jonathan D Stoltzfus

    2014-07-01

    Full Text Available The infectious form of the parasitic nematode Strongyloides stercoralis is a developmentally arrested third-stage larva (L3i, which is morphologically similar to the developmentally arrested dauer larva in the free-living nematode Caenorhabditis elegans. We hypothesize that the molecular pathways regulating C. elegans dauer development also control L3i arrest and activation in S. stercoralis. This study aimed to determine the factors that regulate L3i activation, with a focus on G protein-coupled receptor-mediated regulation of cyclic guanosine monophosphate (cGMP pathway signaling, including its modulation of the insulin/IGF-1-like signaling (IIS pathway. We found that application of the membrane-permeable cGMP analog 8-bromo-cGMP potently activated development of S. stercoralis L3i, as measured by resumption of feeding, with 85.1 ± 2.2% of L3i feeding in 200 µM 8-bromo-cGMP in comparison to 0.6 ± 0.3% in the buffer diluent. Utilizing RNAseq, we examined L3i stimulated with DMEM, 8-bromo-cGMP, or the DAF-12 nuclear hormone receptor (NHR ligand Δ7-dafachronic acid (DA--a signaling pathway downstream of IIS in C. elegans. L3i stimulated with 8-bromo-cGMP up-regulated transcripts of the putative agonistic insulin-like peptide (ILP -encoding genes Ss-ilp-1 (20-fold and Ss-ilp-6 (11-fold in comparison to controls without stimulation. Surprisingly, we found that Δ7-DA similarly modulated transcript levels of ILP-encoding genes. Using the phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitor LY294002, we demonstrated that 400 nM Δ7-DA-mediated activation (93.3 ± 1.1% L3i feeding can be blocked using this IIS inhibitor at 100 µM (7.6 ± 1.6% L3i feeding. To determine the tissues where promoters of ILP-encoding genes are active, we expressed promoter::egfp reporter constructs in transgenic S. stercoralis post-free-living larvae. Ss-ilp-1 and Ss-ilp-6 promoters are active in the hypodermis and neurons and the Ss-ilp-7 promoter is active in the

  9. Effect of co-free valve on activity reduction in PWR

    International Nuclear Information System (INIS)

    Bahn, C.B.; Han, B.C.; Bum, J.S.; Hwang, I.S.; Lee, C.B.

    2002-01-01

    Radioactive nuclei, such as 68 Co and 60 Co, deposited on out-of-core surfaces in a pressurized water reactor (PWR) primary coolant system, are major sources of occupational radiation exposure to plant maintenance personnel and act as costly impediment to prompt and effective repairs. Valve hardfacing alloys exposed to primary coolant are considered as one of the main Co sources. To evaluate the Co-free valve, such as NOREM 02 and Deloro 50, the candidates for the alternative to Stellite 6, in a simulated PWR primary condition, SNU corrosion test loop (SCOTL) was constructed. For gate valves hard-faced with made of NOREM 02 and Deloro 50 hot cycling tests were conducted for up to 2,000 on-off cycles with cold leak tests at 1,000 cycle interval. It was observed that the leak rate of NOREM 02 (Fe-base) did not satisfy the nuclear grade valve leak criteria. After 1000 cycles test, while there was no leakage in case of Deloro 50 (Ni-base). Also, Deloro 50 showed no leakage after 2000 cycles. To estimate the activity reduction effect, we modified CRUDSIM-MIT which modeled the effects of coolant chemistry on the crud transport and activity buildup in the primary system of PWR. In the new code, crud evaluation and assessment (CREAT), 60 Co activity buildup prediction includes 1) Co-base valve replacement effect, 2) Co-base valve maintenance effect, and 3) control rod drive mechanism (CRDM) and main coolant pump (MCP) shaft contribution. CREAT predicted that the main contributor of Co activity buildup was the corrosion-induced release of Co from the steam generator (SG) tubing. With new SG's tubed with alloy 690, Korean Next Generation Reactor (APR-1400) is expected to have about 64% lower Co activity on SG surface. The use of all Co-free valves is expected to cut additional 8% of activity which is only marginal. (authors)

  10. Changes in the physiological activity of soybean (Glycine max L. Merr. under the influence of exogenous growth regulators

    Directory of Open Access Journals (Sweden)

    Anna Nowak

    2015-07-01

    Full Text Available In a two-year pot experiment (2008–2009 conducted at the Vegetation Hall, West Pomeranian University of Technology in Szczecin, we investigated the influence of exogenous growth regulators, i.e. indole-3-butyric acid (IBA and 6-benzylaminopurine (BAP and their mixture, on the activity of gas exchange and selected physiological features of soybeans (Glycine max L. Merr.. The experimental factors included the following Polish soybean cultivars: ‘Aldana’, ‘Progres’ and ‘Jutro’. During plant growth, CO2 assimilation (A, transpiration rate (E, stomatal conductance (gs, and substomatal CO2 concentration (ci were determined. Two soybean cultivars, i.e. ‘Jutro’ and ‘Progres’, showed a significant increase in the intensity of assimilation and transpiration after using all kinds of growth regulators as compared with the control plants. It was found that the ‘Jutro’ cultivar, after using a mixture of growth regulators (IBA + BAP, was characterized by the significantly highest CO2 assimilation (A and transpiration (E as well as the highest stomatal conductance (gs. The ‘Aldana’ cultivar, on the other hand, responded by a significant reduction in the transpiration rate, stomatal conductance and subsomatal CO2 concentration. The spraying of the plants with exogenous growth regulators had a significant influence on the increase in the number of stomata and stomatal pore length, mostly on the lower epidermis of the lamina. It was also found that plants from the ‘Jutro’ and ‘Aldana’ cultivars sprayed with IBA and IBA + BAP were characterized by the highest yield, as compared with the control plants. In the case of the ‘Jutro’ cultivar, after using the growth regulators, a positive correlation was observed between the assimilation and transpiration rates and the length of stomata, which in consequence produced increased yields.

  11. Active sites of ligand-protected Au25 nanoparticle catalysts for CO2 electroreduction to CO

    Science.gov (United States)

    Alfonso, Dominic R.; Kauffman, Douglas; Matranga, Christopher

    2016-05-01

    Recent experimental studies have reported the electrochemical reduction of carbon dioxide (CO2) into CO at atomically precise negatively charged Au25- nanoclusters. The studies showed CO2 conversion at remarkably low overpotentials, but the exact mechanisms and nature of the active sites remain unclear. We used first-principles density functional theory and continuum solvation models to examine the role of the cluster during electrochemical CO2 reduction and analyze the free energies of proposed intermediate species. Contrary to previous assumptions, our results show that the fully ligand protected cluster is not an active CO2 reduction catalyst because formation of the crucial carboxyl intermediate required very high electrochemical potentials. Instead, our calculations suggest that the reduction process likely occurs on a dethiolated gold site, and adsorbed carboxyl intermediate formation was significantly stabilized at dethiolated gold sites. These findings point to the crucial role of exposed metal sites during electrochemical CO2 reduction at gold nanocluster catalysts.

  12. The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease.

    Science.gov (United States)

    Fries, Gabriel R; Gassen, Nils C; Rein, Theo

    2017-12-05

    Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The development leading to the focus on FKBP51 is outlined. Further, a survey of the vast literature on the mechanism and function of FKBP51 is provided. This includes its structure and biochemical function, its regulation on different levels-transcription, post-transcription, and post-translation-and its function in signaling pathways. The evidence portraying FKBP51 as a scaffolding protein organizing protein complexes rather than a chaperone contributing to the folding of individual proteins is collated. Finally, FKBP51's involvement in physiology and disease is outlined, and the promising efforts in developing drugs targeting FKBP51 are discussed.

  13. Synergism in regulation of nuclear and radiological activities

    International Nuclear Information System (INIS)

    Buzdugan, A.

    2009-01-01

    In 2006 the reform of nuclear activity regulation in Moldova was initiated. On May 11, 2006, the Parliament of the Republic of Moldova passed the law Nr 111-XVI 'About Safe Accomplishment of Nuclear and Radiological Activity'. On the 23rd of March, 2007 the National Agency for Regulation of Nuclear and Radiological Activities (NARNRA) was founded due to the decree of the Government under the Ministry of Ecology and Natural Resources. Its first objective was elaboration of necessary regulation documents in this field

  14. Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts

    International Nuclear Information System (INIS)

    Dudas, Jozsef; Fullar, Alexandra; Bitsche, Mario; Schartinger, Volker; Kovalszky, Ilona; Sprinzl, Georg Mathias; Riechelmann, Herbert

    2011-01-01

    Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1β (IL1-β) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-β expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-β processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-β. IL1-β signaling was investigated by western blot and immunocytochemistry. IL1-β-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-β, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NFκBα. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-β reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-β-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-β in the tumor cells leads to IL1-β-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-β. PDL fibroblasts possess receptor for IL1-β, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-β receptor expression in

  15. Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: Mario.Bitsche@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: Volker.Schartinger@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: Herbert.Riechelmann@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

    2011-09-10

    Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the

  16. Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation.

    Science.gov (United States)

    Bjørn, S F; Hastrup, N; Lund, L R; Danø, K; Larsen, J F; Pyke, C

    1997-08-01

    The spatial expression of mRNA for matrix metalloproteinase 2 (MMP-2), its putative activator, the membrane-type 1 matrix metalloproteinase (MT1-MMP), and the MMP-2 substrate type IV collagen was investigated in human placentas of both normal and tubal ectopic pregnancies and in cyclic endometrium using in-situ hybridization. Cytokeratin staining applied to adjacent sections was used to identify epithelial and trophoblast cells. In both normal and tubal pregnancies MT1-MMP, MMP-2 and type IV collagen mRNA were highly expressed and co-localized in the extravillous cytotrophoblasts of anchoring villi, in cytotrophoblasts that had penatrated into the placental bed and in cytotrophoblastic cell islands. In addition, the decidual cells of normal pregnancies in some areas co-expressed MT1-MMP and MMP-2 mRNA, with moderate signals for both components. Fibroblast-like stromal cells in tubal pregnancies were positive for MMP-2 mRNA but generally negative for MT1-MMP mRNA. The consistent co-localization of MT1-MMP with MMP-2 and type IV collagen in the same subset of cytotrophoblasts strongly suggests that all three components co-operate in the tightly regulated fetal invasion process. The co-expression of MT1-MMP and MMP-2 mRNA in some of the decidual cells indicates that these cells are also actively involved in the placentation process.

  17. The Agency's technical co-operation activities in 1992

    International Nuclear Information System (INIS)

    1993-08-01

    This report on the International Atomic Energy Agency's Technical Co-operation Activities in 1992 contains an overview of the general issues involved, including both in-house and external developments, resources and delivery, and evaluation of programs; an overview by field of activity and by division within the Agency; an overview by geographic area, distinguishing (i) Africa, (ii) Asia and the Pacific, (iii) Latin America, (iv) and the Middle East and Europe; an overview by component (i.e., experts, equipment, fellowships, training courses, sub-contracts and miscellaneous); and an overview by fund technical assistance and co-operation fund, extrabudgetary resources, United Nations Development Program (UNDP), assistance in kind. It also contains a profile on technical co-operation activities in Latin America. Projects concluded during 1992 are listed together with a description of their achievements. It concludes with implementation summaries. 10 figs, 9 tabs

  18. RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation.

    Science.gov (United States)

    Wu, Xiangbing; Walker, Chandler L; Lu, Qingbo; Wu, Wei; Eddelman, Daniel B; Parish, Jonathan M; Xu, Xiao-Ming

    2017-11-01

    Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A 2 (cPLA 2 ), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level. We found that co-administration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA 2 . Inhibition of RhoA, Rho kinase and cPLA 2 significantly reduced TNF-α/glutamate-induced cell death by 33, 52 and 43 %, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly downregulated cPLA 2 activation by 66 and 60 %, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA 2 . The immunofluorescence staining showed that ROCK 1 or ROCK 2 , two isoforms of Rho kinase, was co-localized with cPLA 2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK 1 or ROCK 2 bonded directly with cPLA 2 and phospho-cPLA 2 . When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA 2 activation and expression and reduced injury-induced apoptosis at and close to the lesion site. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA 2 activation.

  19. Commission de regulation de l'energie. activity report 2011

    International Nuclear Information System (INIS)

    2012-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2011 activity report of CRE. Contents: 1 - Board of Commissioners' Message; 2 - The operation of the CRE and the activity of CoRDiS (Standing Committee for disputes and sanctions); 3 - Overview of the electricity and gas retail markets; 4 - Third energy package and certification; 5 - Europe of Energy; 6 - Renewable energy; 7 - Nome law (law on the reorganisation of the electricity market); 8 - Gas tariff; 9 - Linky smart meter; 10 - Gas distribution tariff and smart meter; 11 - Appendix: Summary of the CRE's main decisions in 2011

  20. Student profiling on university co-curriculum activities using data visualization tools

    Science.gov (United States)

    Jamil, Jastini Mohd.; Shaharanee, Izwan Nizal Mohd

    2017-11-01

    Co-curricular activities are playing a vital role in the development of a holistic student. Co-curriculum can be described as an extension of the formal learning experiences in a course or academic program. There are many co-curriculum activities such as students' participation in sports, volunteerism, leadership, entrepreneurship, uniform body, student council, and other social events. The number of student involves in co-curriculum activities are large, thus creating an enormous volume of data including their demographic facts, academic performance and co-curriculum types. The task for discovering and analyzing these information becomes increasingly difficult and hard to comprehend. Data visualization offer a better ways in handling with large volume of information. The need for an understanding of these various co-curriculum activities and their effect towards student performance are essential. Visualizing these information can help related stakeholders to become aware of hidden and interesting information from large amount of data drowning in their student data. The main objective of this study is to provide a clearer understanding of the different trends hidden in the student co-curriculum activities data with related to their activities and academic performances. The data visualization software was used to help visualize the data extracted from the database.

  1. Gene co-regulation is highly conserved in the evolution of eukaryotes and prokaryotes.

    NARCIS (Netherlands)

    Snel, B.; Noort, V. van; Huynen, M.A.

    2004-01-01

    Differences between species have been suggested to largely reside in the network of connections among the genes. Nevertheless, the rate at which these connections evolve has not been properly quantified. Here, we measure the extent to which co-regulation between pairs of genes is conserved over

  2. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate

  3. Hessian-regularized co-training for social activity recognition.

    Science.gov (United States)

    Liu, Weifeng; Li, Yang; Lin, Xu; Tao, Dacheng; Wang, Yanjiang

    2014-01-01

    Co-training is a major multi-view learning paradigm that alternately trains two classifiers on two distinct views and maximizes the mutual agreement on the two-view unlabeled data. Traditional co-training algorithms usually train a learner on each view separately and then force the learners to be consistent across views. Although many co-trainings have been developed, it is quite possible that a learner will receive erroneous labels for unlabeled data when the other learner has only mediocre accuracy. This usually happens in the first rounds of co-training, when there are only a few labeled examples. As a result, co-training algorithms often have unstable performance. In this paper, Hessian-regularized co-training is proposed to overcome these limitations. Specifically, each Hessian is obtained from a particular view of examples; Hessian regularization is then integrated into the learner training process of each view by penalizing the regression function along the potential manifold. Hessian can properly exploit the local structure of the underlying data manifold. Hessian regularization significantly boosts the generalizability of a classifier, especially when there are a small number of labeled examples and a large number of unlabeled examples. To evaluate the proposed method, extensive experiments were conducted on the unstructured social activity attribute (USAA) dataset for social activity recognition. Our results demonstrate that the proposed method outperforms baseline methods, including the traditional co-training and LapCo algorithms.

  4. Hessian-regularized co-training for social activity recognition.

    Directory of Open Access Journals (Sweden)

    Weifeng Liu

    Full Text Available Co-training is a major multi-view learning paradigm that alternately trains two classifiers on two distinct views and maximizes the mutual agreement on the two-view unlabeled data. Traditional co-training algorithms usually train a learner on each view separately and then force the learners to be consistent across views. Although many co-trainings have been developed, it is quite possible that a learner will receive erroneous labels for unlabeled data when the other learner has only mediocre accuracy. This usually happens in the first rounds of co-training, when there are only a few labeled examples. As a result, co-training algorithms often have unstable performance. In this paper, Hessian-regularized co-training is proposed to overcome these limitations. Specifically, each Hessian is obtained from a particular view of examples; Hessian regularization is then integrated into the learner training process of each view by penalizing the regression function along the potential manifold. Hessian can properly exploit the local structure of the underlying data manifold. Hessian regularization significantly boosts the generalizability of a classifier, especially when there are a small number of labeled examples and a large number of unlabeled examples. To evaluate the proposed method, extensive experiments were conducted on the unstructured social activity attribute (USAA dataset for social activity recognition. Our results demonstrate that the proposed method outperforms baseline methods, including the traditional co-training and LapCo algorithms.

  5. Reversible inactivation of CO dehydrogenase with thiol compounds

    Energy Technology Data Exchange (ETDEWEB)

    Kreß, Oliver [Department of Microbiology, University of Bayreuth, 95440 Bayreuth (Germany); Gnida, Manuel [Department of Chemistry, University of Paderborn, 33098 Paderborn (Germany); Pelzmann, Astrid M. [Department of Microbiology, University of Bayreuth, 95440 Bayreuth (Germany); Marx, Christian [Institute of Biochemistry and Biophysics, Friedrich-Schiller-University of Jena, 07745 Jena (Germany); Meyer-Klaucke, Wolfram [Department of Chemistry, University of Paderborn, 33098 Paderborn (Germany); Meyer, Ortwin, E-mail: Ortwin.Meyer@uni-bayreuth.de [Department of Microbiology, University of Bayreuth, 95440 Bayreuth (Germany)

    2014-05-09

    Highlights: • Rather large thiols (e.g. coenzyme A) can reach the active site of CO dehydrogenase. • CO- and H{sub 2}-oxidizing activity of CO dehydrogenase is inhibited by thiols. • Inhibition by thiols was reversed by CO or upon lowering the thiol concentration. • Thiols coordinate the Cu ion in the [CuSMo(=O)OH] active site as a third ligand. - Abstract: Carbon monoxide dehydrogenase (CO dehydrogenase) from Oligotropha carboxidovorans is a structurally characterized member of the molybdenum hydroxylase enzyme family. It catalyzes the oxidation of CO (CO + H{sub 2}O → CO{sub 2} + 2e{sup −} + 2H{sup +}) which proceeds at a unique [CuSMo(=O)OH] metal cluster. Because of changing activities of CO dehydrogenase, particularly in subcellular fractions, we speculated whether the enzyme would be subject to regulation by thiols (RSH). Here we establish inhibition of CO dehydrogenase by thiols and report the corresponding K{sub i}-values (mM): L-cysteine (5.2), D-cysteine (9.7), N-acetyl-L-cysteine (8.2), D,L-homocysteine (25.8), L-cysteine–glycine (2.0), dithiothreitol (4.1), coenzyme A (8.3), and 2-mercaptoethanol (9.3). Inhibition of the enzyme was reversed by CO or upon lowering the thiol concentration. Electron paramagnetic resonance spectroscopy (EPR) and X-ray absorption spectroscopy (XAS) of thiol-inhibited CO dehydrogenase revealed a bimetallic site in which the RSH coordinates to the Cu-ion as a third ligand ([Mo{sup VI}(=O)OH{sub (2)}SCu{sup I}(SR)S-Cys]) leaving the redox state of the Cu(I) and the Mo(VI) unchanged. Collectively, our findings establish a regulation of CO dehydrogenase activity by thiols in vitro. They also corroborate the hypothesis that CO interacts with the Cu-ion first. The result that thiol compounds much larger than CO can freely travel through the substrate channel leading to the bimetallic cluster challenges previous concepts involving chaperone function and is of importance for an understanding how the sulfuration step in

  6. Supercritical CO2 Compressor with Active Magnetic Bearing

    International Nuclear Information System (INIS)

    Cha, Jae Eun; Cho, Seong Kuk; Lee, JeKyoung; Lee, Jeong Ik

    2016-01-01

    For the stable operation of the sCO 2 integral test facility SCIEL, KAERI prepared Active Magnetic Bearing sCO 2 compressor for the 70,000RPM operation. Power generation test with AMB compressor will be finished within first half year of 2016 under supercritical state. The principal advantages of the sCO 2 Cycle are high efficiency at moderate temperature range, compact components size, simple cycle configuration, and compatibility with various heat sources. The Supercritical CO 2 Brayton Cycle Integral Experiment Loop (SCIEL) has been installed in Korea Atomic Energy Research Institute (KAERI) to develop the base technologies for the sCO 2 cycle power generation system. The operation of the SCIEL has mainly focused on sCO 2 compressor development and establishing sCO 2 system control logic

  7. Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

    International Nuclear Information System (INIS)

    Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

    2006-01-01

    Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

  8. The E1A proteins of all six human adenovirus subgroups target the p300/CBP acetyltransferases and the SAGA transcriptional regulatory complex

    International Nuclear Information System (INIS)

    Shuen, Michael; Avvakumov, Nikita; Torchia, Joe; Mymryk, Joe S.

    2003-01-01

    The N-terminal/conserved region 1 (CR1) portion of the human adenovirus (Ad) 5 E1A protein was previously shown to inhibit growth in the simple eukaryote Saccharomyces cerevisiae. We now demonstrate that the corresponding regions of the E1A proteins of Ad3,-4,-9,-12, and -40, which represent the remaining five Ad subgroups, also inhibit yeast growth. These results suggest that the E1A proteins of all six human Ad subgroups share a common cellular target(s) conserved in yeast. Growth inhibition induced by either full-length or the N-terminal/CR1 portion of Ad5 E1A was relieved by coexpression of the E1A binding portions of the mammalian p300, CBP, and pCAF acetyltransferases. Similarly, growth inhibition by the N-terminal/CR1 portions of the other Ad E1A proteins was suppressed by expression of the same regions of CBP or pCAF known to bind Ad5 E1A. The physical interaction of each of the different Ad E1A proteins with CBP, p300, and pCAF was confirmed in vitro. Furthermore, deletion of the gene encoding yGcn5, the yeast homolog of pCAF and a subunit of the SAGA transcriptional regulatory complex, restored growth in yeast expressing each of the different Ad E1A proteins. This indicates that the SAGA complex is a conserved target of all Ad E1A proteins. Our results demonstrate for the first time that the p300, CBP, and pCAF acetyltransferases are common targets for the E1A proteins of all six human Ad subgroups, highlighting the importance of these interactions for E1A function

  9. Identification of HMG-CoA Reductase Inhibitor Active Compound in Medicinal Forest Plants

    Directory of Open Access Journals (Sweden)

    Shelly Rahmania

    2017-08-01

    Full Text Available Cardiovascular disease is a leading cause of death worldwide, hypercholesterolemia is one of the causes. Three medicinal forest plants are potential natural resources to be developed as cholesterol-reducing herbal product, but scientific informations on their mechanism is still limited. The objective of this research is to explore the potency of the leaf of Jati Belanda (Guazuma ulmifolia, Jabon (Antocephalus macrophyllus, and Mindi (Melia azedarach as inhibitor of HMG-CoA reductase (HMGR, a key enzyme in the regulation of cholesterol biosynthesis. Samples were macerated in ethanol 96% and the filtrate was partitioned using n-hexane and chloroform to obtain the ethanolic flavonoid extract. The effect of each extracts on the HMG-CoA reductase activity were analyzed using HMGR assay kit. At concentration of 10 ppm the G.ulmifolia ethanolic extract showed the highest inhibitory activity as well as pravastatin control inhibitor.  The phenolic content of the ethanolic extracts of G.ulmifolia, A.macrophyllus, and M.azedarach were: 11.00, 34.83, and 13.67 mg gallic acid AE/g dried leaves, respectively. The flavonoid content of the ethanolic extracts of G.ulmifolia, A.macrophyllus, and M.azedarach were: 0.22, 0.64, and 0.78 mg QE/g dried leaves, respectively. Interestingly, G.ulmifolia extract the lowest concentration of phenolic and flavonoid content. HPLC analysis showed that all samples contain quercetin at similiar small concentrations (6.7%, 6.6%, and 7.0% for G.ulmifolia, A.macrophyllus, and M.azedarach, respectively. This indicating other active compounds may play some roles in this inhibitory action on HMG-CoA reductase activity. Further identification using LC-MS/MS showed that G.ulmifolia flavonoid extract contained an unidetified coumpound with molecural weight of 380.0723 Da.  

  10. Drought responses of two gymnosperm species with contrasting stomatal regulation strategies under elevated [CO2] and temperature.

    Science.gov (United States)

    Duan, Honglang; O'Grady, Anthony P; Duursma, Remko A; Choat, Brendan; Huang, Guomin; Smith, Renee A; Jiang, Yanan; Tissue, David T

    2015-07-01

    Future climate regimes characterized by rising [CO2], rising temperatures and associated droughts may differentially affect tree growth and physiology. However, the interactive effects of these three factors are complex because elevated [CO2] and elevated temperature may generate differential physiological responses during drought. To date, the interactive effects of elevated [CO2] and elevated temperature on drought-induced tree mortality remain poorly understood in gymnosperm species that differ in stomatal regulation strategies. Water relations and carbon dynamics were examined in two species with contrasting stomatal regulation strategies: Pinus radiata D. Don (relatively isohydric gymnosperm; regulating stomata to maintain leaf water potential above critical thresholds) and Callitris rhomboidea R. Br (relatively anisohydric gymnosperm; allowing leaf water potential to decline as the soil dries), to assess response to drought as a function of [CO2] and temperature. Both species were grown in two [CO2] (C(a) (ambient, 400 μl l(-1)) and C(e) (elevated, 640 μl l(-1))) and two temperature (T(a) (ambient) and T(e) (ambient +4 °C)) treatments in a sun-lit glasshouse under well-watered conditions. Drought plants were then exposed to a progressive drought until mortality. Prior to mortality, extensive xylem cavitation occurred in both species, but significant depletion of non-structural carbohydrates was not observed in either species. Te resulted in faster mortality in P. radiata, but it did not modify the time-to-mortality in C. rhomboidea. C(e) did not delay the time-to-mortality in either species under drought or T(e) treatments. In summary, elevated temperature (+4 °C) had greater influence than elevated [CO2] (+240 μl l(-1)) on drought responses of the two studied gymnosperm species, while stomatal regulation strategies did not generally affect the relative contributions of hydraulic failure and carbohydrate depletion to mortality under severe drought.

  11. Production of activated carbons from coffee endocarp by CO2 and steam activation

    International Nuclear Information System (INIS)

    Nabais, Joao M. Valente; Nunes, Pedro; Carrott, Peter J.M.; Ribeiro Carrott, M. Manuela L.; Garcia, A. Macias; Diaz-Diez, M.A.

    2008-01-01

    In this work the use of coffee endocarp as precursor for the production of activated carbons by steam and CO 2 was studied. Activation by both methods produces activated carbons with small external areas and microporous structures having very similar mean pore widths. The activation produces mainly primary micropores and only a small volume of larger micropores. The CO 2 activation leads to samples with higher BET surface areas and pore volumes when compared with samples produced by steam activation and with similar burn-off value. All the activated carbons produced have basic characteristics with point of zero charge between 10 and 12. By FTIR it was possible to identify the formation on the activated carbon's surface of several functional groups, namely ether, quinones, lactones, ketones, hydroxyls (free and phenol); pyrones and Si-H bonds. (author)

  12. Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

    Science.gov (United States)

    Matamales, Miriam

    2012-12-19

    Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

  13. PLAG1 and USF2 Co-regulate Expression of Musashi-2 in Human Hematopoietic Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Muluken S. Belew

    2018-04-01

    Full Text Available Summary: MSI2, which is expressed predominantly in hematopoietic stem and progenitor cells (HSPCs, enforces HSPC expansion when overexpressed and is upregulated in myeloid leukemias, indicating its regulated transcription is critical to balanced self-renewal and leukemia restraint. Despite this, little is understood of the factors that enforce appropriate physiological levels of MSI2 in the blood system. Here, we define a promoter region that reports on endogenous expression of MSI2 and identify USF2 and PLAG1 as transcription factors whose promoter binding drives reporter activity. We show that these factors co-regulate, and are required for, efficient transactivation of endogenous MSI2. Coincident overexpression of USF2 and PLAG1 in primitive cord blood cells enhanced MSI2 transcription and yielded cellular phenotypes, including expansion of CD34+ cells in vitro, consistent with that achieved by direct MSI2 overexpression. Global chromatin immunoprecipitation sequencing analyses confirm a preferential co-binding of PLAG1 and USF2 at the promoter of MSI2, as well as regulatory regions corresponding to genes with roles in HSPC homeostasis. PLAG1 and USF2 cooperation is thus an important contributor to stem cell-specific expression of MSI2 and HSPC-specific transcriptional circuitry. : MSI2 is an essential human hematopoietic stem and progenitor cell (HSPC regulator, but knowledge of the mechanisms ensuring its appropriate expression in this context are lacking. Here, Hope and colleagues map the MSI2 promoter functional in hematopoietic cells and identify USF2 and PLAG1 as essential, cooperative enforcers of endogenous MSI2 expression and stemness traits in human HSPCs. Keywords: human hematopoietic stem cells, self-renewal, promoter, transcriptional regulation, transcription factors, Musashi-2, genome-wide DNA binding site mapping, PLAG1, USF2

  14. Adaxial/abaxial specification in the regulation of photosynthesis and stomatal opening with respect to light orientation and growth with CO2 enrichment in the C4 species Paspalum dilatatum.

    Science.gov (United States)

    Soares, Ana Sofia; Driscoll, Simon P; Olmos, Enrique; Harbinson, Jeremy; Arrabaça, Maria Celeste; Foyer, Christine H

    2008-01-01

    Whole-plant morphology, leaf structure and composition were studied together with the effects of light orientation on the dorso-ventral regulation of photosynthesis and stomatal conductance in Paspalum dilatatum cv. Raki plants grown for 6 wk at either 350 or 700 microl l(-1) CO(2). Plant biomass was doubled as a result of growth at high CO(2) and the shoot:root ratio was decreased. Stomatal density was increased in the leaves of the high CO(2)-grown plants, which had greater numbers of smaller stomata and more epidermal cells on the abaxial surface. An asymmetric surface-specific regulation of photosynthesis and stomatal conductance was observed with respect to light orientation. This was not caused by dorso-ventral variations in leaf structure, the distribution of phosphoenolpyruvate carboxylase (PEPC) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) proteins or light absorptance, transmittance or reflectance. Adaxial/abaxial specification in the regulation of photosynthesis results from differential sensitivity of stomatal opening to light orientation and fixed gradients of enzyme activation across the leaf.

  15. Activity of ISO9001:2015 certification that Fuji Electric Co., LTD. (Nuclear Power Division) performed

    International Nuclear Information System (INIS)

    Nitta, Kazuhiko; Umetsu, Hiroyuki; Takahashi, Masaaki; Hosoda, Hiroshi

    2017-01-01

    Regarding the certification transition to ISO9001:2015 version, this paper introduces the contents of the revision to the 2015 version, contents of activities until the certification transition performed by Fuji Electric Co. Nuclear Power Division, and outline of the quality management system (QMS) that was established. The main contents of the revision are as follows; (1) 2015 version is composed of the unification of various management structure standards existing in ISO standards, (2) integration of business and QMS based on the understanding of organization's situation and the needs and expectations of stakeholders, (3) introduction of risk-based concept on preventive actions, (4) strengthening of leadership, (5) emphasis on performance (conversion to output matters), and (6) strengthening, addition, and expansion of the specific requirements of QMS. Regarding the certification transition activities of Fuji Electric Co. Nuclear Power Division, the schedule goal was set as transition examination with about two years of allowance, and the activities thereafter were as follows; (1) extract of the revised parts of division regulations and formulation of revision policy, (2) revision of quality manual, and implementation of gap analysis, (3) formulation of division regulations by the working group, (4) 6 months of pilot operation, and (5) acceptance of transition examination. As a result of the transition, QMS has been strengthened as described below, and customers have given greater trust. The strengthening of QMS is composed of the accumulation of organization's knowledge (specific technology) and its daily practice, which helped the company to form the organization that can prevent beforehand the problems caused by risks and opportunities in face of business management. (A.O.)

  16. Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes

    International Nuclear Information System (INIS)

    Ryu, Jae-Sung; Jung, Yeon-Hwa; Cho, Mi-Young; Yeo, Jee Eun; Choi, Yun-Jin; Kim, Yong Il; Koh, Yong-Gon

    2014-01-01

    Highlights: • Co-culture of hSDMSCs with SNP-stimulated chondrocytes improves anti-inflammation. • Co-culture system produces IGF-1. • Co-culture system suppresses inflammatory genes expression. • Co-culture system improves cell proliferation. • Exogenous IGF-1 inhibits inflammatory activity in SNP-stimulated chondrocytes. - Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA

  17. Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jae-Sung; Jung, Yeon-Hwa; Cho, Mi-Young; Yeo, Jee Eun; Choi, Yun-Jin; Kim, Yong Il; Koh, Yong-Gon, E-mail: yonseranglab@daum.net

    2014-05-16

    Highlights: • Co-culture of hSDMSCs with SNP-stimulated chondrocytes improves anti-inflammation. • Co-culture system produces IGF-1. • Co-culture system suppresses inflammatory genes expression. • Co-culture system improves cell proliferation. • Exogenous IGF-1 inhibits inflammatory activity in SNP-stimulated chondrocytes. - Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.

  18. FY 2000 report on the promotion projects by Research Institute of Innovative Technology for the Earth. Proceedings of the international seminar (Reports on photosynthetic CO2-assimilating enzymes by the international workshops); 2000 nendo chikyu kankyo sangyo gijutsu kaihatsu suishin jigyo kokusai seminar jigyo shiryo. Kogosei CO2 kotei koso kokusai workshop hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    Described herein are the reports on photosynthetic CO2-assimilating enzymes, presented to the international symposium. These enzymes are important for assimilating CO2 in air, maintaining the environments and production of foods. For genes and proteins, the topics include diversification and function evolution of the RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) in the natural environments, in particular in microorganisms. For activity regulation of PEPC, the topics include three-dimensional structures of PEPC and phosphorylation mechanisms and activity regulation therefor. For activity regulation of RuBisCO, the topics include post-translational activity of the enzymes (e.g., methylated enzyme); molecular regulation mechanisms involved in the biosynthesis and decomposition of RuBisCO; and activity regulation mechanisms in the chloroplast. For leaf photosynthesis and RuBisCO, the topics include importance of enzymes and involved in-vivo reaction steps for leaf photosynthesis CO2 assimilation reactions. For function of PEPC, the topics include the biochemically and molecular biologically necessary and sufficient conditions for the C4 mechanism as the special photosynthesis mechanism. For transgenic approaches, the topics include procedure for allowing the RuBisCO gene of a dissimilar organism to function in the tobacco chloroplast, and introduction of enzymes involved in the C4 photosynthesis pathway in C3 plants. (NEDO)

  19. Magnetic properties of iron-based catalysts activated by various CO{sub 2} concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jung Tae; Kim, Chul Sung [Kookmin University, Seoul (Korea, Republic of); Chun, Dong Hyun; Park, Ji Chan [Korea Institute of Energy Research, Daejeon (Korea, Republic of)

    2014-12-15

    Fresh catalyst samples of 100Fe/5.26Cu/4.76K/18.2SiO{sub 2} in part per weight were synthesized by using a combination of a co-precipitation technique and spray-drying method and were activated in situ by using syngas (H{sub 2}/CO/xCO{sub 2}) with different amounts of CO{sub 2} (x = 0.0, 0.5, 1.0, and 2.0). All activated catalyst samples showed similar XRD patterns, a combination of ferrihydrite, magnetite, χ-carbide, and ε'-carbide, regardless of the CO{sub 2} contents. From the Moessbauer spectra, we also observed a combination of ferrihydrite, magnetite, χ-carbide, and ε'-carbide in all activated catalyst samples. The main compound of the activated catalyst sample activated by using CO{sub 2}-free syngas (H{sub 2}/CO) was magnetic χ-carbide, and the main compound changed from χ-carbide to ferrihydrite with increasing CO{sub 2} concentration, confirmed by both, Moessbauer spectra and XRD pattern.

  20. Regulation of CO2 markets. Report of the mission entrusted to Michel PRADA, honorary Finance general inspector

    International Nuclear Information System (INIS)

    2009-01-01

    This report first discusses the current operation of the CO 2 emission permit European market and notices that its development took place in a context characterized by a light, incomplete and heterogeneous regulation, and that it therefore needs a better framework to make a carbon price emerge which will be robust on a long term in Europe. It shows that this market is presently mainly a by-product market and must be better structured. It highlights the uncertainty due to the lack of a homogeneous law qualification of CO 2 emission permits. It stresses the need of a stronger control of participants while preserving the open market principle, the need of a greater transparency and greater regulation stability, the implementation of a prevention and sanction framework. It proposes a quick setting up of a supervision architecture integrated to the CO 2 European market

  1. Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons.

    Science.gov (United States)

    Dhar, Shilpa S; Liang, Huan Ling; Wong-Riley, Margaret T T

    2009-10-01

    Neuronal activity is highly dependent on energy metabolism; yet, the two processes have traditionally been regarded as independently regulated at the transcriptional level. Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical subunits of glutamatergic receptors. The present study tests our hypothesis that the co-regulation extends to the next level of glutamatergic synapses, namely, neuronal nitric oxide synthase, which generates nitric oxide as a downstream signaling molecule. Using in silico analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, promoter mutations, and NRF-1 silencing, we documented that NRF-1 functionally bound to Nos1, but not Nos2 (inducible) and Nos3 (endothelial) gene promoters. Both COX and Nos1 transcripts were up-regulated by depolarizing KCl treatment and down-regulated by TTX-mediated impulse blockade in neurons. However, NRF-1 silencing blocked the up-regulation of both Nos1 and COX induced by KCl depolarization, and over-expression of NRF-1 rescued both Nos1 and COX transcripts down-regulated by TTX. These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level.

  2. The Effect of CO2 Activation on the Electrochemical Performance of Coke-Based Activated Carbons for Supercapacitors.

    Science.gov (United States)

    Lee, Hye-Min; Kim, Hong-Gun; An, Kay-Hyeok; Kim, Byung-Joo

    2015-11-01

    The present study developed electrode materials for supercapacitors by activating coke-based activated carbons with CO2. For the activation reaction, after setting the temperature at 1,000 degrees C, four types of activated carbons were produced, over an activation time of 0-90 minutes and with an interval of 30 minutes as the unit. The electrochemical performance of the activated carbons produced was evaluated to examine the effect of CO2 activation. The surface structure of the porous carbons activated through CO2 activation was observed using a scanning electron microscope (SEM). To determine the N2/77 K isothermal adsorption characteristics, the Brunauer-Emmett-Teller (BET) equation and the Barrett-Joyner-Halenda (BJH) equation were used to analyze the pore characteristics. In addition, charge and discharge tests and cyclic voltammetry (CV) were used to analyze the electrochemical characteristics of the changed pore structure. According to the results of the experiments, the N2 adsorption isotherm curves of the porous carbons produced belonged to Type IV in the International Union of Pore and Applied Chemistry (IUPAC) classification and consisted of micropores and mesopores, and, as the activation of CO2 progressed, micropores decreased and mesopores developed. The specific surface area of the porous carbons activated by CO2 was 1,090-1,180 m2/g and thus showed little change, but those of mesopores were 0.43-0.85 cm3/g, thus increasing considerably. In addition, when the electrochemical characteristics were analyzed, the specific capacity was confirmed to have increased from 13.9 F/g to 18.3 F/g. From these results, the pore characteristics of coke-based activated carbons changed considerably because of CO2 activation, and it was therefore possible to increase the electrochemical characteristics.

  3. The integrative omics of white-rot fungus Pycnoporus coccineus reveals co-regulated CAZymes for orchestrated lignocellulose breakdown.

    Directory of Open Access Journals (Sweden)

    Shingo Miyauchi

    Full Text Available Innovative green technologies are of importance for converting plant wastes into renewable sources for materials, chemicals and energy. However, recycling agricultural and forestry wastes is a challenge. A solution may be found in the forest. Saprotrophic white-rot fungi are able to convert dead plants into consumable carbon sources. Specialized fungal enzymes can be utilized for breaking down hard plant biopolymers. Thus, understanding the enzymatic machineries of such fungi gives us hints for the efficient decomposition of plant materials. Using the saprotrophic white-rot fungus Pycnoporus coccineus as a fungal model, we examined the dynamics of transcriptomic and secretomic responses to different types of lignocellulosic substrates at two time points. Our integrative omics pipeline (SHIN+GO enabled us to compress layers of biological information into simple heatmaps, allowing for visual inspection of the data. We identified co-regulated genes with corresponding co-secreted enzymes, and the biological roles were extrapolated with the enriched Carbohydrate-Active Enzyme (CAZymes and functional annotations. We observed the fungal early responses for the degradation of lignocellulosic substrates including; 1 simultaneous expression of CAZy genes and secretion of the enzymes acting on diverse glycosidic bonds in cellulose, hemicelluloses and their side chains or lignin (i.e. hydrolases, esterases and oxido-reductases; 2 the key role of lytic polysaccharide monooxygenases (LPMO; 3 the early transcriptional regulation of lignin active peroxidases; 4 the induction of detoxification processes dealing with biomass-derived compounds; and 5 the frequent attachments of the carbohydrate binding module 1 (CBM1 to enzymes from the lignocellulose-responsive genes. Our omics combining methods and related biological findings may contribute to the knowledge of fungal systems biology and facilitate the optimization of fungal enzyme cocktails for various

  4. SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4.

    Science.gov (United States)

    Perdomo, José; Jiang, Xing-Mai; Carter, Daniel R; Khachigian, Levon M; Chong, Beng H

    2012-01-01

    Friend of GATA 2 (FOG-2), a co-factor of several GATA transcription factors (GATA-4, -5 and 6), is a critical regulator of coronary vessel formation and heart morphogenesis. Here we demonstrate that FOG-2 is SUMOylated and that this modification modulates its transcriptional activity. FOG-2 SUMOylation occurs at four lysine residues (K324, 471, 915, 955) [corrected]. Three of these residues are part of the characteristic SUMO consensus site (ψKXE), while K955 is found in the less frequent TKXE motif. Absence of SUMOylation did not affect FOG-2's nuclear localization. However, mutation of the FOG-2 SUMOylation sites, or de-SUMOylation, with SENP-1 or SENP-8 resulted in stronger transcriptional repression activity in both heterologous cells and cardiomyocytes. Conversely, increased FOG-2 SUMOylation by overexpression of SUMO-1 or expression of a SUMO-1-FOG-2 fusion protein rendered FOG-2 incapable of repressing GATA-4-mediated activation of the B-type natriuretic peptide (BNP) promoter. Moreover, we demonstrate both increased interaction between a FOG-2 SUMO mutant and GATA-4 and enhanced SUMOylation of wild-type FOG-2 by co-expression of GATA-4. These data suggest a new dynamics in which GATA-4 may alter the activity of FOG-2 by influencing its SUMOylation status.

  5. Activity-regulated genes as mediators of neural circuit plasticity.

    Science.gov (United States)

    Leslie, Jennifer H; Nedivi, Elly

    2011-08-01

    Modifications of neuronal circuits allow the brain to adapt and change with experience. This plasticity manifests during development and throughout life, and can be remarkably long lasting. Evidence has linked activity-regulated gene expression to the long-term structural and electrophysiological adaptations that take place during developmental critical periods, learning and memory, and alterations to sensory map representations in the adult. In all these cases, the cellular response to neuronal activity integrates multiple tightly coordinated mechanisms to precisely orchestrate long-lasting, functional and structural changes in brain circuits. Experience-dependent plasticity is triggered when neuronal excitation activates cellular signaling pathways from the synapse to the nucleus that initiate new programs of gene expression. The protein products of activity-regulated genes then work via a diverse array of cellular mechanisms to modify neuronal functional properties. Synaptic strengthening or weakening can reweight existing circuit connections, while structural changes including synapse addition and elimination create new connections. Posttranscriptional regulatory mechanisms, often also dependent on activity, further modulate activity-regulated gene transcript and protein function. Thus, activity-regulated genes implement varied forms of structural and functional plasticity to fine-tune brain circuit wiring. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

    Science.gov (United States)

    Han, Xinxin; Yin, Linlin; Xue, Hongwei

    2012-07-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

  7. NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d.

    Science.gov (United States)

    Kuylenstierna, Carlotta; Björkström, Niklas K; Andersson, Sofia K; Sahlström, Peter; Bosnjak, Lidija; Paquin-Proulx, Dominic; Malmberg, Karl-Johan; Ljunggren, Hans-Gustaf; Moll, Markus; Sandberg, Johan K

    2011-07-01

    Invariant NKT cells are important in the activation and regulation of immune responses. They can also function as CD1d-restricted killer cells. However, the role of activating innate NK-cell receptors expressed on NKT cells in triggering cytolytic function is poorly characterized. Here, we initially confirmed that the cellular stress-ligand receptor NKG2D is expressed on CD4- NKT cells, whereas most CD4+ NKT cells lack this receptor. Interestingly, NKG2D+ NKT cells frequently expressed perforin, and both NKG2D and perforin localized at the site of contact with NKG2D ligand-expressing target cells. CD4- NKT cells degranulated in response to NKG2D engagement in a redirected activation assay independent of stimulation via their invariant TCR. NKT cells killed P815 cells coated with anti-NKG2D mAb and CD1d-negative K562 tumor target cells in an NKG2D-dependent manner. Furthermore, NKG2D engagement co-stimulated TCR-mediated NKT-cell activation in response to endogenous CD1d-presented ligands or suboptimal levels of anti-CD3 triggering. These data indicate that the CD4- subset of human NKT cells can mediate direct lysis of target cells via NKG2D engagement independent of CD1d, and that NKG2D also functions as a co-stimulatory receptor in these cells. NKG2D thus plays both a direct and a co-stimulatory role in the activation of NKT cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. The Liver X Receptor Ligand T0901317 Down-regulates APOA5 GeneExpression through Activation of SREBP-1c

    Energy Technology Data Exchange (ETDEWEB)

    Jakel, Heidelinde; Nowak, Maxime; Moitrot, Emanuelle; Dehondt, Helene; Hum, Dean W.; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart,Jean-Charles

    2004-07-23

    Alterations in the expression of the recently discovered apolipoprotein A5 gene strongly affect plasma triglyceride levels. In this study, we investigated the contribution of APOA5 to the liver X-receptor (LXR) ligand mediated effect on plasma triglyceride levels.Following treatment with the LXR ligand T0901317, we found that APOA5mRNA levels were decreased in hepatoma cell lines. The observation that no down-regulation of APOA5 promoter activity was obtained by LXR-retinoid X receptor (RXR) co-transfection prompted us to explore the possible involvement of the known LXR target gene SREBP-1c (sterol regulatory element-binding protein 1c). In fact, we found that co-transfection with the active form of SREBP-1c down-regulated APOA5promoter activity in a dose-dependent manner. We then scanned the human APOA5 promoter sequence and identified two putative E-box elements that were able to bind specifically SREBP-1c in gel-shift assays and were shown to be functional by mutation analysis. Subsequent suppression of SREBP-1 mRNA through small interfering RNA interference abolished the decrease of APOA5 mRNA in response to T0901317. Finally, administration of T0901317 to hAPOA5 transgenic mice revealed a significant decrease OF APOA5 mRNA in liver tissue and circulating apolipoprotein AV protein in plasma, confirming that the described down-regulation also occurs in vivo. Taken together, our results demonstrate that APOA5 gene expression is regulated by the LXR ligand T0901317 in a negative manner through SREBP-1c. These findings may provide a new mechanism responsible for the elevation of plasma triglyceride levels by LXR ligands and support the development of selective LXR agonists, not affecting SREBP-1c, as beneficial modulators of lipid metabolism.

  9. Recycling CO 2 ? Computational Considerations of the Activation of CO 2 with Homogeneous Transition Metal Catalysts

    KAUST Repository

    Drees, Markus; Cokoja, Mirza; Kü hn, Fritz E.

    2012-01-01

    . A similar approach, storing energy from renewable sources in chemical bonds with CO 2 as starting material, may lead to partial recycling of CO 2 created by human industrial activities. Unfortunately, currently available routes for the transformation

  10. The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein

    International Nuclear Information System (INIS)

    Pearson, Joel D; Mohammed, Zubair; Bacani, Julinor T C; Lai, Raymond; Ingham, Robert J

    2012-01-01

    Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. These translocations generate fusion proteins (e.g. NPM-ALK) with constitutive tyrosine kinase activity, which activate numerous signalling pathways important for ALK+ ALCL pathogenesis. The molecular chaperone heat shock protein-90 (Hsp90) plays a critical role in allowing NPM-ALK and other signalling proteins to function in this lymphoma. Co-chaperone proteins are important for helping Hsp90 fold proteins and for directing Hsp90 to specific clients; however the importance of co-chaperone proteins in ALK+ ALCL has not been investigated. Our preliminary findings suggested that expression of the immunophilin co-chaperone, Cyclophilin 40 (Cyp40), is up-regulated in ALK+ ALCL by JunB, a transcription factor activated by NPM-ALK signalling. In this study we examined the regulation of the immunophilin family of co-chaperones by NPM-ALK and JunB, and investigated whether the immunophilin co-chaperones promote the viability of ALK+ ALCL cell lines. NPM-ALK and JunB were knocked-down in ALK+ ALCL cell lines with siRNA, and the effect on the expression of the three immunophilin co-chaperones: Cyp40, FK506-binding protein (FKBP) 51, and FKBP52 examined. Furthermore, the effect of knock-down of the immunophilin co-chaperones, either individually or in combination, on the viability of ALK+ ALCL cell lines and NPM-ALK levels and activity was also examined. We found that NPM-ALK promoted the transcription of Cyp40 and FKBP52, but only Cyp40 transcription was promoted by JunB. We also observed reduced viability of ALK+ ALCL cell lines treated with Cyp40 siRNA, but not with siRNAs directed against FKBP52 or FKBP51. Finally, we demonstrate that the decrease in the viability of ALK+ ALCL cell lines treated with Cyp40 siRNA does not appear to be due to a decrease in NPM-ALK levels or the

  11. [Regulation of alternative CO[sub 2] fixation pathways in procaryotic and eucaryotic photosynthetic organisms

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

    The major goal of this project is to determine how microorganisms regulate the assimilation of CO[sup 2] via pathways alternative to the usual Calvin reductive pentose phosphate scheme. In particular, we are interest in the molecular basis for switches in CO[sub 2] metabolic paths. Several earlier studies had indicated that purple nonsulfur photosynthetic bacteria assimilate significant amounts of CO[sub 2] via alternative non-Calvin routes. We have deleted the gene that encodes. RubisCo (ribulose bisphosphate carboxylase/oxygenase) in both the Rhodobacter sphaeroids and Rhodospirillum rubrum. The R. sphaeroides RubisCO deletion strain (strain 16) could not grow under photoheterotrophic conditions with malate as electron donor and CO[sub 2] as the electron acceptor; however the R. rub RubisCO deletion strain (strain I-19) could. Over the past year we have sought to physiologically characterize strain 16PHC. We found that, 16PHC exhibited rates of whole-cell CO[sub 2] fixation which were significantly higher than strain 16. Strain 16PHC could not grow photolithoautotrophically in a CO[sub 2] atmosphere; however, CO[sub 2] fixation catalyzed by photoheterotrophically grown 16PHC was repressed by the addition of DMSO. Likewise, we found that cells initially grown in the presence of DMSO could induce the CO[sub 2] fixation system when DMSO was removed. Thus, these results suggested that both PHC and I-19 could be used to study alternative CO[sub 2] fixation reactions and their significance in R. sphaexoides and R. rubrum.

  12. Recycling CO 2 ? Computational Considerations of the Activation of CO 2 with Homogeneous Transition Metal Catalysts

    KAUST Repository

    Drees, Markus

    2012-08-10

    Faced with depleting fossil carbon sources, the search for alternative energy carriers and energy storage possibilities has become an important issue. Nature utilizes carbon dioxide as starting material for storing sun energy in plant hydrocarbons. A similar approach, storing energy from renewable sources in chemical bonds with CO 2 as starting material, may lead to partial recycling of CO 2 created by human industrial activities. Unfortunately, currently available routes for the transformation of CO 2 involve high temperatures and are often not selective. With the development of more sophisticated methods and better software, theoretical studies have become both increasingly widespread and useful. This concept article summarizes theoretical investigations of the current state of the feasibility of CO 2 activation with molecular transition metal catalysts, highlighting the most promising reactions of CO 2 with olefins to industrially relevant acrylic acid/acrylates, and the insertion of CO 2 into metal-element bonds, particularly for the synthesis of cyclic carbonates and polymers. Rapidly improving computational power and methods help to increase the importance and accuracy of calculations continuously and make computational chemistry a useful tool helping to solve some of the most important questions for the future. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Identification and characterization of an archaeal ketopantoate reductase and its involvement in regulation of coenzyme A biosynthesis.

    Science.gov (United States)

    Tomita, Hiroya; Imanaka, Tadayuki; Atomi, Haruyuki

    2013-10-01

    Coenzyme A (CoA) biosynthesis in bacteria and eukaryotes is regulated primarily by feedback inhibition towards pantothenate kinase (PanK). As most archaea utilize a modified route for CoA biosynthesis and do not harbour PanK, the mechanisms governing regulation of CoA biosynthesis are unknown. Here we performed genetic and biochemical studies on the ketopantoate reductase (KPR) from the hyperthermophilic archaeon Thermococcus kodakarensis. KPR catalyses the second step in CoA biosynthesis, the reduction of 2-oxopantoate to pantoate. Gene disruption of TK1968, whose product was 20-29% identical to previously characterized KPRs from bacteria/eukaryotes, resulted in a strain with growth defects that were complemented by addition of pantoate. The TK1968 protein (Tk-KPR) displayed reductase activity specific for 2-oxopantoate and preferred NADH as the electron donor, distinct to the bacterial/eukaryotic NADPH-dependent enzymes. Tk-KPR activity decreased dramatically in the presence of CoA and KPR activity in cell-free extracts was also inhibited by CoA. Kinetic studies indicated that CoA inhibits KPR by competing with NADH. Inhibition of ketopantoate hydroxymethyltransferase, the first enzyme of the pathway, by CoA was not observed. Our results suggest that CoA biosynthesis in T. kodakarensis is regulated by feedback inhibition of KPR, providing a feasible regulation mechanism of CoA biosynthesis in archaea. © 2013 John Wiley & Sons Ltd.

  14. Regulation of CO{sub 2} markets. Report of the mission entrusted to Michel PRADA, honorary Finance general inspector; La regulation des marches du CO{sub 2}. Rapport de la mission confiee a Michel PRADA, Inspecteur general des Finances honoraire

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    This report first discusses the current operation of the CO{sub 2} emission permit European market and notices that its development took place in a context characterized by a light, incomplete and heterogeneous regulation, and that it therefore needs a better framework to make a carbon price emerge which will be robust on a long term in Europe. It shows that this market is presently mainly a by-product market and must be better structured. It highlights the uncertainty due to the lack of a homogeneous law qualification of CO{sub 2} emission permits. It stresses the need of a stronger control of participants while preserving the open market principle, the need of a greater transparency and greater regulation stability, the implementation of a prevention and sanction framework. It proposes a quick setting up of a supervision architecture integrated to the CO{sub 2} European market

  15. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  16. Regulation of schistosome egg production by HMG CoA reductase

    International Nuclear Information System (INIS)

    VandeWaa, E.A.; Bennett, J.L.

    1986-01-01

    Hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase) catalyzes the conversion of HMG CoA to mevalonate in the synthesis of steroids, isoprenoids and terpenes. Mevinolin, an inhibitor of this enzyme, decreased egg production in Schistosoma mansoni during in vitro incubations. This was associated with a reduction in the incorporation of 14 C-acetate into polyisoprenoids and a reduction in the formation of a lipid-linked oligosaccharide. In vivo, mevinolin in daily doses of 50 mg/kg (p.o., from days 30-48 post-infection) caused no change in gross liver pathology in S. mansoni infected mice. However, when parasites exposed to mevinolin or its vehicle in vivo were cultured in vitro, worms from mevinolin-treated mice produced six times more eggs than control parasites. When infected mice were dosed with 250 mg/kg mevinolin daily (p.o., from days 35-45 post-infection), liver pathology was reduced in comparison to control mice. Thus, during in vivo exposure to a high dose of the drug egg production is decreased, while at a lower dose it appears unaffected until the parasites are cultured in a drug-free in vitro system wherein egg production is stimulated to extraordinarily high levels. It may be that at low doses mevinolin, by inhibiting the enzyme, is blocking the formation of a product (such as an isoprenoid) which normally acts to down-regulate enzyme synthesis, resulting in enzyme induction. Induction of HMG CoA reductase is then expressed as increased egg production when the worms are removed from the drug. These data suggest that HMG CoA reductase plays a role in schistosome egg production

  17. Mechanotransductive Regulation of Gap-Junction Activity Between MLO-Y4 Osteocyte-Like and MC3T3-E1 Osteoblast-Like Cells in Three-Dimensional Co-Culture.

    Science.gov (United States)

    Juran, C. M.; Blaber, E. A.; Almeida, E. A. C.

    2016-01-01

    Cell and animal studies conducted onboard the International Space Station and formerly on Shuttle flights have provided groundbreaking data illuminating the deleterious biological response of bone to mechanical unloading. However the intercellular communicative mechanisms associated with the regulation of bone synthesis and bone resorption cells are still largely unknown. Connexin-43 (CX43), a gap junction protein, is hypothesized to play a significant role in osteoblast and osteocyte signaling. The purpose of this investigation was to evaluate within a novel three-dimensional microenvironment how the osteocyte-osteoblast gap-junction expression changes when cultures are exposed to exaggerated mechanical load. MLO-Y4 osteocyte-like cells were cultured on a 3D-Biotek polystyrene insert and placed in direct contact with an MC3T3-E1 pre-osteoblast co-cultured monolayer and exposed to 48 h of mechanical stimulation (pulsatile fluid flow (PFF) or monolayer cyclic stretch (MCS)) then evaluated for viability, proliferation, metabolism, and CX43 expression. Mono-cultured MLO-Y4 and MC3T3-E1 control experiments were conducted under PFF and MCS stimulation to observe how strain application stimuli (PFF cell membrane shear or MCS cell focal adhesion/attachment loading) initiates different signaling pathways or downstream regulatory controls. TotalLive cell count, viability and metabolic reduction (Trypan Blue, LIVEDead and Alamar Blue analysis respectively) indicate that mechanical activation of MC3T3-E1 cells inhibits proliferation while maintaining an average 1.04E4 reductioncell metabolic rate, *p0.05 n4. MLO-Y4s in monolayer culture increase in number when exposed to MCS loading but the percent of live cells within the population is low (46.3 total count, *p0.05 n4), these results may indicate an apoptotic signaling cascade. PFF stimulation of the three-dimensional co-cultures elicits a universal increase in CX43 in MLO-Y4 and MC3T3-E1 cells, illustrated by

  18. 30 CFR 285.1000 - What activities does this subpart regulate?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What activities does this subpart regulate? 285.1000 Section 285.1000 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Activities § 285.1000 What activities does this subpart regulate? (a) This subpart provides the general...

  19. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

    Science.gov (United States)

    Pecorella, Shelly R H; Potter, Jennifer V F; Cherry, Anne D; Peacher, Dionne F; Welty-Wolf, Karen E; Moon, Richard E; Piantadosi, Claude A; Suliman, Hagir B

    2015-10-15

    The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity. Copyright © 2015 the American Physiological Society.

  20. Modules of co-regulated metabolites in turmeric (Curcuma longa) rhizome suggest the existence of biosynthetic modules in plant specialized metabolism.

    Science.gov (United States)

    Xie, Zhengzhi; Ma, Xiaoqiang; Gang, David R

    2009-01-01

    Turmeric is an excellent example of a plant that produces large numbers of metabolites from diverse metabolic pathways or networks. It is hypothesized that these metabolic pathways or networks contain biosynthetic modules, which lead to the formation of metabolite modules-groups of metabolites whose production is co-regulated and biosynthetically linked. To test whether such co-regulated metabolite modules do exist in this plant, metabolic profiling analysis was performed on turmeric rhizome samples that were collected from 16 different growth and development treatments, which had significant impacts on the levels of 249 volatile and non-volatile metabolites that were detected. Importantly, one of the many co-regulated metabolite modules that were indeed readily detected in this analysis contained the three major curcuminoids, whereas many other structurally related diarylheptanoids belonged to separate metabolite modules, as did groups of terpenoids. The existence of these co-regulated metabolite modules supported the hypothesis that the 3-methoxyl groups on the aromatic rings of the curcuminoids are formed before the formation of the heptanoid backbone during the biosynthesis of curcumin and also suggested the involvement of multiple polyketide synthases with different substrate selectivities in the formation of the array of diarylheptanoids detected in turmeric. Similar conclusions about terpenoid biosynthesis could also be made. Thus, discovery and analysis of metabolite modules can be a powerful predictive tool in efforts to understand metabolism in plants.

  1. Supercritical CO{sub 2} Compressor with Active Magnetic Bearing

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Jae Eun [KAERI, Daejeon (Korea, Republic of); Cho, Seong Kuk; Lee, JeKyoung; Lee, Jeong Ik [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    For the stable operation of the sCO{sub 2} integral test facility SCIEL, KAERI prepared Active Magnetic Bearing sCO{sub 2} compressor for the 70,000RPM operation. Power generation test with AMB compressor will be finished within first half year of 2016 under supercritical state. The principal advantages of the sCO{sub 2} Cycle are high efficiency at moderate temperature range, compact components size, simple cycle configuration, and compatibility with various heat sources. The Supercritical CO{sub 2} Brayton Cycle Integral Experiment Loop (SCIEL) has been installed in Korea Atomic Energy Research Institute (KAERI) to develop the base technologies for the sCO{sub 2} cycle power generation system. The operation of the SCIEL has mainly focused on sCO{sub 2} compressor development and establishing sCO{sub 2} system control logic.

  2. Comparison of Surface and Column Variations of CO2 Over Urban Areas for Future Active Remote CO2 Sensors

    Science.gov (United States)

    Choi, Yonghoon; Yang, Melissa; Kooi, Susan; Browell, Edward

    2015-01-01

    High resolution in-situ CO2 measurements were recorded onboard the NASA P-3B during the DISCOVER-AQ (Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality) Field Campaign, to investigate the ability of space-based observations to accurately assess near surface conditions related to air quality. This campaign includes, Washington DC/Baltimore, MD (July 2011), San Joaquin Valley, CA (January - February 2013), Houston, TX (September 2013), and Denver, CO (July-August 2014). Each of these campaigns consisted of missed approaches and approximately two hundred vertical soundings of CO2 within the lower troposphere (surface to about 5 km). In this study, surface (0 - 1 km) and column-averaged (0 - 3.5 km) CO2 mixing ratio values from the vertical soundings in the four geographically different urban areas are used to investigate the temporal and spatial variability of CO2 within the different urban atmospheric emission environments. Tracers such as CO, CH2O, NOx, and NMHCs are used to identify the source of CO2 variations in the urban sites. Additionally, we apply nominal CO2 column weighting functions for potential future active remote CO2 sensors operating in the 1.57-microns and 2.05-microns measurement regions to convert the in situ CO2 vertical mixing ratio profiles to variations in CO2 column optical depths, which is what the active remote sensors actually measure. Using statistics calculated from the optical depths at each urban site measured during the DISCOVER-AQ field campaign and for each nominal weighting function, we investigate the natural variability of CO2 columns in the lower troposphere; relate the CO2 column variability to the urban surface emissions; and show the measurement requirements for the future ASCENDS (Active Sensing of CO2 Emissions over Nights, Days, and Seasons) in the continental U.S. urban areas.

  3. Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: Insights on viral regulation of apoptosis and proliferation

    International Nuclear Information System (INIS)

    Yeung, Y.-S.; Yip, C.-W.; Hon, C.-C.; Chow, Ken Y.C.; Ma, Iris C.M.; Zeng Fanya; Leung, Frederick C.C.

    2008-01-01

    We have previously demonstrated that over-expression of spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) or its C-terminal subunit (S2) is sufficient to induce apoptosis in vitro. To further investigate the possible roles of S2 in SARS-CoV-induced apoptosis and pathogenesis of SARS, we characterized the host expression profiles induced upon S2 over-expression in Vero E6 cells by oligonucleotide microarray analysis. Possible activation of mitochondrial apoptotic pathway in S2 expressing cells was suggested, as evidenced by the up-regulation of cytochrome c and down-regulation of the Bcl-2 family anti-apoptotic members. Inhibition of Bcl-2-related anti-apoptotic pathway was further supported by the diminution of S2-induced apoptosis in Vero E6 cells over-expressing Bcl-xL. In addition, modulation of CCN E2 and CDKN 1A implied the possible control of cell cycle arrest at G1/S phase. This study is expected to extend our understanding on the pathogenesis of SARS at a molecular level

  4. Regulation of palmitoyl-CoA chain elongation by clofibric acid in the liver of Zucker fa/fa rats.

    Science.gov (United States)

    Toyama, Tomoaki; Kudo, Naomi; Mitsumoto, Atsushi; Kawashima, Yoichi

    2005-05-01

    The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4-chlorophenoxy)-2-methylpropionic acid] was investigated in comparison with stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The proportion of oleic acid in the hepatic lipids of Zucker obese rats is 2.7 times higher than that of lean littermates. The activities of PCE and SCD in the liver of Zucker obese rats were markedly higher than in lean rats, and the hepatic uptake of 2-deoxyglucose (2-DG) was also higher in Zucker obese rats compared with lean rats. The increased activities of SCD and PCE in Zucker obese rats were due to the enhanced expression of mRNA of both SCD1 and rat FA elongase 2 (rELO2), but not SCD2 or rELO1. The proportion of oleic acid in the liver was significantly increased by the administration of clofibric acid to Zucker obese rats, and the hepatic PCE activity and rELO2 mRNA expression, but not the SCD activity or SCD1 mRNA expression, were increased in response to clofibric acid treatment. By contrast, the activities of both PCE and SCD and the mRNA expression of SCD1 and rELO2 in the liver were increased by the treatment of Zucker lean rats with clofibric acid. Multiple regression analysis, which was performed to determine the relationships involving PCE activity, SCD activity, and the proportion of oleic acid, revealed that the three parameters were significantly correlated and that the standardized partial regression coefficient of PCE was higher than that of SCD. These results indicate that oleic acid is synthesized by the concerted action of PCE and SCD and that PCE plays a crucial role in the formation of oleic acid when Zucker fa/fa rats are given clofibric acid.

  5. Co-ordinate transcriptional regulation of dopamine synthesis genes by alpha-synuclein in human neuroblastoma cell lines.

    Science.gov (United States)

    Baptista, Melisa J; O'Farrell, Casey; Daya, Sneha; Ahmad, Rili; Miller, David W; Hardy, John; Farrer, Matthew J; Cookson, Mark R

    2003-05-01

    Abnormal accumulation of alpha-synuclein in Lewy bodies is a neuropathological hallmark of both sporadic and familial Parkinson's disease (PD). Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic cell death occurs remains unknown. We investigated transcriptional changes in neuroblastoma cell lines transfected with either normal or mutant (A30P or A53T) alpha-synuclein using microarrays, with confirmation of selected genes by quantitative RT-PCR. Gene products whose expression was found to be significantly altered included members of diverse functional groups such as stress response, transcription regulators, apoptosis-inducing molecules, transcription factors and membrane-bound proteins. We also found evidence of altered expression of dihydropteridine reductase, which indirectly regulates the synthesis of dopamine. Because of the importance of dopamine in PD, we investigated the expression of all the known genes in dopamine synthesis. We found co-ordinated downregulation of mRNA for GTP cyclohydrolase, sepiapterin reductase (SR), tyrosine hydroxylase (TH) and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein. These were confirmed at the protein level for SR and TH. Reduced expression of the orphan nuclear receptor Nurr1 was also noted, suggesting that the co-ordinate regulation of dopamine synthesis is regulated through this transcription factor.

  6. Phytochrome regulates GTP-binding protein activity in the envelope of pea nuclei

    Science.gov (United States)

    Clark, G. B.; Memon, A. R.; Thompson, G. A. Jr; Roux, S. J.

    1993-01-01

    Three GTP-binding proteins with apparent molecular masses of 27, 28 and 30 kDa have been detected in isolated nuclei of etiolated pea plumules. After LDS-PAGE and transfer to nitrocellulose these proteins bind [32P]GTP in the presence of excess ATP, suggesting that they are monomeric G proteins. When nuclei are disrupted, three proteins co-purify with the nuclear envelope fraction and are highly enriched in this fraction. The level of [32P]GTP-binding for all three protein bands is significantly increased when harvested pea plumules are irradiated by red light, and this effect is reversed by far-red light. The results indicate that GTP-binding activity associated with the nuclear envelope of plant cells is photoreversibly regulated by the pigment phytochrome.

  7. Institutional preconditions of socio-ecological-economic regulation of environmental management activities

    Directory of Open Access Journals (Sweden)

    T. A. Plaksunova

    2017-01-01

    Full Text Available The need to regulate environmental management activities of institutional entities arises when it affects the interests of third-party entities or threatened by the ongoing entity manufacturing practices its own resilience, to achieve the main goal. The complexity and diversity of the forms of socio-ecological and ecological-economic issues at different levels of the economic system leads to the development of many directions and views on the expansion of the management process of these levels (global, national, regional, local and techniques from rigid-deklorative state before combination with the market. In this respect, the neoclassical economic theory actively generated new analytical ideas and concept that enables to respond adequately to emerging economic realities. So we can distinguish the following approaches to regulate environmental management activities: T. Malthus and D. Ricardo, revealing issues of social, ecological and economic implications of limited natural resources in the context of the law of diminishing effectiveness and the need to regulate environmental management activities. John. St. Mill and George proved to be ineffective in addressing environmental problems in the industrial economy of the type of the imperfection of the institutions of society, justifying the occurrence of crises protohistoric speculation nature's benefits. A. Pigou developed the theory of externalities, which revealed the need for state regulation of the environmental management activities of economic entities, harmonization of individual and social interests. Research I. Kula, F. Khan and P. Samuelson identified a pattern about the formation of the system of regulation nature-safety activities, not only within individual States but also on a global level. R. Crows have shown that the methods of direct state regulation of nature economic activity is not as good as it seems at first glance and so you should not underestimate the role and potential

  8. Soil Gas Dynamics and Microbial Activity in the Unsaturated Zone of a Regulated River

    Science.gov (United States)

    Christensen, H.; Ferencz, S. B.; Cardenas, M. B.; Neilson, B. T.; Bennett, P. C.

    2017-12-01

    Over 60% of the world's rivers are dammed, and are therefore regulated. In some river systems, river regulation is the dominant factor governing fluid exchange and soil gas dynamics in the hyporheic region and overlying unsaturated zone of the river banks. Where this is the case, it is important to understand the effects that an artificially-induced change in river stage can have on the chemical, plant, and microbial components of the unsaturated zone. Daily releases from an upstream dam cause rapid stage fluctuations in the Lower Colorado River east of Austin, Texas. For this study, we utilized an array of water and gas wells along a transect perpendicular to the river to investigate the biogeochemical process occurring in this mixing zone. The gas wells were installed at several depths up to 1.5 meters, and facilitated the continuous monitoring of soil gases as the pulse percolated through the river bank. Water samples collected from the screened wells penetrated to depths below the water table and were analyzed for nutrients, carbon, and major ions. Additionally, two soil cores were taken at different distances from the river and analyzed for soil moisture and grain size. These cores were also analyzed for microbial activity using the total heterotroph count method and the acetylene inhibition technique, a sensitive method of measuring denitrifying activity. The results provide a detailed picture of soil gas flux and biogeochemical processes in the bank environment in a regulated river. Findings indicate that a river pulse that causes a meter-scale change in river stage causes small, centimeter-scale pulses in the water table. We propose that these conditions create an area of elevated microbial respiration at the base of the unsaturated zone that appears to be decoupled from normal diurnal fluctuations. Along the transect, CO2 concentrations increased with increasing depth down to the water table. CO2 concentrations were highest in the time following a pulse

  9. Regulation of invadopodia formation and activity by CD147

    Science.gov (United States)

    Grass, G. Daniel; Bratoeva, Momka; Toole, Bryan P.

    2012-01-01

    A defining feature of malignant tumor progression is cellular penetration through the basement membrane and interstitial matrices that separate various cellular compartments. Accumulating evidence supports the notion that invasive cells employ specialized structures termed invadopodia to breach these structural barriers. Invadopodia are actin-based, lipid-raft-enriched membrane protrusions containing membrane-type-1 matrix metalloproteinase (MT1-MMP; also known as matrix metalloproteinase 14; MMP14) and several signaling proteins. CD147 (emmprin, basigin), an immunoglobulin superfamily protein that is associated with tumor invasion and metastasis, induces the synthesis of various matrix metalloproteinases in many systems. In this study we show that upregulation of CD147 is sufficient to induce MT1-MMP expression, invasiveness and formation of invadopodia-like structures in non-transformed, non-invasive, breast epithelial cells. We also demonstrate that CD147 and MT1-MMP are in close proximity within these invadopodia-like structures and co-fractionate in membrane compartments with the properties of lipid rafts. Moreover, manipulation of CD147 levels in invasive breast carcinoma cells causes corresponding changes in MT1-MMP expression, invasiveness and invadopodia formation and activity. These findings indicate that CD147 regulates invadopodia formation and activity, probably through assembly of MT1-MMP-containing complexes within lipid-raft domains of the invadopodia. PMID:22389410

  10. Plants increase laccase activity in soil with long-term elevated CO2 legacy

    DEFF Research Database (Denmark)

    Partavian, Asrin; Mikkelsen, Teis Nørgaard; Vestergård, Mette

    2015-01-01

    [CO2] stimulate laccase activity. We incubated soil exposed to seven years of elevated or ambient field [CO2] in ambient or elevated [CO2] chambers for six months either with or without plants (Deschampsia flexuosa). Elevated chamber [CO2] increased D. flexuosa production and belowground respiration....... Interestingly, plants also grew larger in soil with an elevated [CO2] legacy. Plants stimulated soil microbial biomass, belowground respiration and laccase activity, and the plant-induced laccase stimulation was particularly apparent in soil exposed to long-term elevated [CO2] in the field, whereas laccase......Actively growing plants can stimulate mineralization of recalcitrant soil organic matter (SOM), and increased atmospheric [CO2] can further enhance such plant-mediated SOM degradation. Laccases are central for recalcitrant SOM decomposition, and we therefore hypothesized that plants and elevated...

  11. Post-translational regulation of Oct4 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Jonathan P Saxe

    Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

  12. Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

    2015-12-01

    Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

    Science.gov (United States)

    Agarwal, Neeti; Iyer, Dinakar; Patel, Sanjeet G.; Sekhar, Rajagopal V.; Phillips, Terry M.; Schubert, Ulrich; Oplt, Toni; Buras, Eric D.; Samson, Susan L.; Couturier, Jacob; Lewis, Dorothy E.; Rodriguez-Barradas, Maria C.; Jahoor, Farook; Kino, Tomoshige; Kopp, Jeffrey B.; Balasubramanyam, Ashok

    2014-01-01

    Viral infections, such as HIV, have been linked to obesity, but mechanistic evidence that they cause adipose dysfunction in vivo is lacking. We investigated a pathogenic role for the HIV-1 accessory protein viral protein R (Vpr), which can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome proliferator–activated receptor γ (PPARγ) in vitro, in HIV-associated adipose dysfunction. Vpr circulated in the blood of most HIV-infected patients tested, including those on antiretroviral therapy (ART) with undetectable viral load. Vpr-mediated mechanisms were dissected in vivo using mouse models expressing the Vpr transgene in adipose tissues and liver (Vpr-Tg) or infused with synthetic Vpr. Both models demonstrated accelerated whole-body lipolysis, hyperglycemia and hypertriglyceridemia, and tissue-specific findings. Fat depots in these mice had diminished mass, macrophage infiltration, and blunted PPARγ target gene expression but increased GR target gene expression. In liver, we observed blunted PPARα target gene expression, steatosis with decreased adenosine monophosphate– activated protein kinase activity, and insulin resistance. Similar to human HIV-infected patients, Vpr circulated in the serum of Vpr-Tg mice. Vpr blocked differentiation in preadipocytes through cell cycle arrest, whereas in mature adipocytes, it increased lipolysis with reciprocally altered association of PPARγ and GR with their target promoters. These results delineate a distinct pathogenic sequence: Vpr, released from HIV-1 in tissue reservoirs after ART, can disrupt PPAR/GR co-regulation and cell cycle control to produce adipose dysfunction and hepatosteatosis. Confirmation of these mechanisms in HIV patients could lead to targeted treatment of the metabolic complications with Vpr inhibitors, GR antagonists, or PPARγ/PPARα agonists. PMID:24285483

  14. SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4.

    Directory of Open Access Journals (Sweden)

    José Perdomo

    Full Text Available Friend of GATA 2 (FOG-2, a co-factor of several GATA transcription factors (GATA-4, -5 and 6, is a critical regulator of coronary vessel formation and heart morphogenesis. Here we demonstrate that FOG-2 is SUMOylated and that this modification modulates its transcriptional activity. FOG-2 SUMOylation occurs at four lysine residues (K324, 471, 915, 955 [corrected]. Three of these residues are part of the characteristic SUMO consensus site (ψKXE, while K955 is found in the less frequent TKXE motif. Absence of SUMOylation did not affect FOG-2's nuclear localization. However, mutation of the FOG-2 SUMOylation sites, or de-SUMOylation, with SENP-1 or SENP-8 resulted in stronger transcriptional repression activity in both heterologous cells and cardiomyocytes. Conversely, increased FOG-2 SUMOylation by overexpression of SUMO-1 or expression of a SUMO-1-FOG-2 fusion protein rendered FOG-2 incapable of repressing GATA-4-mediated activation of the B-type natriuretic peptide (BNP promoter. Moreover, we demonstrate both increased interaction between a FOG-2 SUMO mutant and GATA-4 and enhanced SUMOylation of wild-type FOG-2 by co-expression of GATA-4. These data suggest a new dynamics in which GATA-4 may alter the activity of FOG-2 by influencing its SUMOylation status.

  15. Self- and Co-regulation of Anger and Fear in Preschoolers with Autism Spectrum Disorders: The Role of Maternal Parenting Style and Temperament.

    Science.gov (United States)

    Hirschler-Guttenberg, Yael; Feldman, Ruth; Ostfeld-Etzion, Sharon; Laor, Nathaniel; Golan, Ofer

    2015-09-01

    Emotion regulation (ER) difficulties are a major concern in children with autism spectrum disorder (ASD). Maternal temperament and parenting style have significant effects on children's ER. However, these effects have not been studied in children with ASD. Forty preschoolers with ASD and their mothers and forty matched controls engaged in fear and anger ER paradigms, micro-coded for child self- and co-regulatory behaviors and parent's regulation-facilitation. Mothers' parenting style and temperament were self-reported. In the ASD group only, maternal authoritarian style predicted higher self-regulation and lower co-regulation of anger and maternal authoritative style predicted higher self-regulation of fear. Maternal temperament did not predict child's ER. Findings emphasize the importance of maternal flexible parenting style in facilitating ER among children with ASD.

  16. Influence Of Dilution Factor For Activity Measurement Of 60CO

    International Nuclear Information System (INIS)

    Hermawan-Candra; Nazaroh; Ermi-Juita

    2003-01-01

    Influence of dilution factor for activity measurement of 60 Co has been studied. The aim of this research is to determine influence between activity measurement result of 60 Co before and after diluted. Measurement were done by using ionization chamber detectors system and gamma spectrometry system with NaI(TI) detector. Discrepancy within three ionization chambers measurements were 0.2% - 2.1% and NaI(Tl) were 3.5% - 6%. (author)

  17. Activation of ion transport systems during cell volume regulation

    International Nuclear Information System (INIS)

    Eveloff, J.L.; Warnock, D.G.

    1987-01-01

    This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na + -H + and Cl - -HCO 3 - exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K + and Cl - conductances, a K-Cl cotransport system, or parallel K + -H + and Cl - -HCO 3 - exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca 2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na + -H + and Cl - -HCO 3 - exchange systems

  18. Making carbon dioxide sequestration feasible: Toward federal regulation of CO2 sequestration pipelines

    International Nuclear Information System (INIS)

    Mack, Joel; Endemann, Buck

    2010-01-01

    As the United States moves closer to a national climate change policy, it will have to focus on a variety of factors affecting the manner in which the country moves toward a future with a substantially lower carbon footprint. In addition to encouraging renewable energy, smart grid, clean fuels and other technologies, the United States will need to make substantial infrastructure investments in a variety of industries. Among the significant contributors to the current carbon footprint in the United States is the use of coal as a major fuel for the generation of electricity. One of the most important technologies that the United States can employ to reduce its carbon footprint is to sequester the carbon dioxide ('CO 2 ') from coal-fired power plants. This article focuses on the legal and policy issues surrounding a critical piece of the necessary sequestration infrastructure: CO 2 pipelines that will carry CO 2 from where it is removed from fuel or waste gas streams to where it will be sequestered. Ultimately, this article recommends developing a federally regulated CO 2 pipeline program to foster the implementation of carbon sequestration technology.

  19. Development strategies to satisfy corporate average CO_2 emission regulations of light duty vehicles (LDVs) in Korea

    International Nuclear Information System (INIS)

    Oh, Yunjung; Park, Junhong; Lee, Jong Tae; Seo, Jigu; Park, Sungwook

    2016-01-01

    In the present study, we generated vehicle dynamic based light-duty vehicle (LDV) models and investigated some technical strategies in order to meet the corporate average CO_2 emission (CACE) regulations of Korea, which will be applied from 2016 to 2020. Seven types of LDV simulation models (including gasoline, diesel, and hybrid cars) were generated based on the AVL CRUISE program and the LDV sales ratio was used to estimate the CACE value of five companies in Korea. The prediction accuracy of the LDV models was validated using chassis dynamometer test data. Then, the effectiveness of the CACE reduction strategies was investigated based on the developed LDV simulation models. From the results of this study, it was revealed that all of the companies cannot satisfy the 2020 CACE regulation by just adopting a single strategy. In order to solve this problem, two types of CACE plans that combined several strategies (reducing the mass drag and fuel consumption rate, and adding a hybrid module, etc.) were proposed. After implementing the two types of CACE plan, it was predicted that five companies will be able to satisfy the 2020 CACE regulation. - Highlights: • Seven types of LDV models were generated to predict CO_2 emission. • Five companies were selected as the major car makers in Korea. • Diverse of strategies were considered to meet the future CO_2 standards in Korea. • All of the companies cannot satisfy the 2020 regulation by adopting a single item. • Two types of plans that combined several strategies were proposed.

  20. Id1 expression promotes peripheral CD4{sup +} T cell proliferation and survival upon TCR activation without co-stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chen; Jin, Rong [Department of Immunology, Peking University Health Science Center, Beijing (China); Wang, Hong-Cheng [Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Tang, Hui; Liu, Yuan-Feng; Qian, Xiao-Ping; Sun, Xiu-Yuan; Ge, Qing [Department of Immunology, Peking University Health Science Center, Beijing (China); Sun, Xiao-Hong, E-mail: sunx@omrf.org [Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Zhang, Yu, E-mail: zhangyu007@bjmu.edu.cn [Department of Immunology, Peking University Health Science Center, Beijing (China)

    2013-06-21

    Highlights: •Id1 expression enables naïve T cell proliferation without anti-CD28 co-stimulation. •Id1 expression facilitates T cells survival when stimulated with anti-CD3. •Elevation of IL-2 production by Id1 contributes increased proliferation and survival. •Id1 potentiates NF-κB activation by anti-CD3 stimulation. -- Abstract: Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïve CD4{sup +} cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.

  1. The Legitimation of Self-Regulation and Co-Regulation in Corporatist Concepts of Legal Scholars in the Weimar Republic

    Directory of Open Access Journals (Sweden)

    Peter Collin

    2017-03-01

    Full Text Available Corporatist regulation has a hybrid structure in that it covers state regulation, regulated self-regulation as well as private-public co-regulation. Notably diverging from the standard mode of state regulation, such arrangements required a higher degree of legitimation. Corporatist concepts flourished in the Weimar Republic. This paper deals with three legal scholars’ considerations regarding how to legitimize corporatist models, namely Edgar Tatarin-Tarnheyden, Heinrich Herrfahrdt, and Friedrich Glum. Their institutional touchstone was the Imperial Economic Council, as provided for by article 165 of the Weimar Constitution. This article envisioned a multi-level system of economic councils ranging from regional economic councils up to the Imperial Economic Council and involving representatives of all occupational groups in the performance of state tasks. However, only a Provisional Imperial Economic Council, with a restricted consultative remit, was ever actually established. Based on this model, Tatarin-Tarnheyden, Heinrich Herrfahrdt, and Friedrich Glum conceptualized organizational structures aiming at the comprehensive inclusion of non-state actors. They were legitimized primarily with reference to their output; that is, these organizational forms were supposed to enable a more appropriate and efficient realization of public interests. The input-based argument was basically a question of participation, which implies considerable proximity to typical topoi of democratic legitimation. This similarity is perhaps counter-intuitive, given that corporatist concepts are traditionally associated with anti-democratic ideologies due to their anti-parliamentarian slant. The numerous points of convergence between corporatist and democratic thought simultaneously reflect the heterogeneity of democratic reasoning in the Weimar period and the openness for ideas that were sceptical of—or even hostile to—parliamentary democracy and the party

  2. Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

    Directory of Open Access Journals (Sweden)

    Jeon Hyejin

    2012-06-01

    Full Text Available Abstract Background Plasminogen activator inhibitor type 1 (PAI-1 is the primary inhibitor of urokinase type plasminogen activators (uPA and tissue type plasminogen activators (tPA, which mediate fibrinolysis. PAI-1 is also involved in the innate immunity by regulating cell migration and phagocytosis. However, little is known about the role of PAI-1 in the central nervous system. Methods In this study, we identified PAI-1 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry. Secretion of PAI-1 from glial cultures was detected by ELISA and western blotting analysis. Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model. Phagocytic activity was measured by uptake of zymosan particles. Results The levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP 1/Janus kinase (JAK/signal transducer and activator of transcription (STAT1 axis. PAI-1 also increased microglial migration in vivo when injected into mouse brain. PAI-1-mediated microglial migration was independent of protease inhibition, because an R346A mutant of PAI-1 with impaired PA inhibitory activity also promoted microglial migration. Moreover, PAI-1 was able to modulate microglial phagocytic activity. PAI-1 inhibited microglial engulfment of zymosan particles in a vitronectin- and Toll-like receptor 2/6-dependent manner. Conclusion Our results indicate that glia-derived PAI-1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner. This may have important implications in the regulation of brain microglial activities in health and disease.

  3. Markets, prices and regulation in energetic activities

    International Nuclear Information System (INIS)

    Percebois, Jacques

    2015-09-01

    The author first outlines some fundamental characteristics of the different energy world markets (oil, natural gas, coal, electricity). He outlines their availability, locations, and different main geographical areas. Then, he discusses the relationships between costs and prices in which intervene external costs, taxes, feed-in tariffs, national regulations, incentives for consumers. He discusses the issue of regulation of some energy activities, i.e. how State may or may not intervene on the markets, how competition may influence the market, how activities can thus be divided (production, transport, distribution) with implications and consequences for prices. He finally outlines concerns about the future financing of investments required to face tomorrow's needs

  4. OCA-B regulation of B-cell development and function.

    Science.gov (United States)

    Teitell, Michael A

    2003-10-01

    The transcriptional co-activator OCA-B [for Oct co-activator from B cells, also known as OBF-1 (OCT-binding factor-1) and Bob1] is not required for B-cell genesis but does regulate subsequent B-cell development and function. OCA-B deficient mice show strain-specific, partial blocks at multiple stages of B-cell maturation and a complete disruption of germinal center formation in all strains, causing humoral immune deficiency and susceptibility to infection. OCA-B probably exerts its effects through the regulation of octamer-motif controlled gene expression. The OCA-B gene encodes two proteins of distinct molecular weight, designated p34 and p35. The p34 isoform localizes in the nucleus, whereas the p35 isoform is myristoylated and is bound to the cytoplasmic membrane. p35 can traffic to the nucleus and probably activates octamer-dependent transcription, although this OCA-B isoform might regulate B cells through membrane-related signal transduction.

  5. Nickel and low CO2-controlled motility in Chlamydomonas through complementation of a paralyzed flagella mutant with chemically regulated promoters

    Directory of Open Access Journals (Sweden)

    Rosenbaum Joel L

    2011-01-01

    Full Text Available Abstract Background Chlamydomonas reinhardtii is a model system for the biology of unicellular green algae. Chemically regulated promoters, such as the nickel-inducible CYC6 or the low CO2-inducible CAH1 promoter, may prove useful for expressing, at precise times during its cell cycle, proteins with relevant biological functions, or complementing mutants in genes encoding such proteins. To this date, this has not been reported for the above promoters. Results We fused the CYC6 and CAH1 promoters to an HA-tagged RSP3 gene, encoding a protein of the flagellar radial spoke complex. The constructs were used for chemically regulated complementation of the pf14 mutant, carrying an ochre mutation in the RSP3 gene. 7 to 8% of the transformants showed cells with restored motility after induction with nickel or transfer to low CO2 conditions, but not in non-inducing conditions. Maximum complementation (5% motile cells was reached with very different kinetics (5-6 hours for CAH1, 48 hours for CYC6. The two inducible promoters drive much lower levels of RSP3 protein expression than the constitutive PSAD promoter, which shows almost complete rescue of motility. Conclusions To our knowledge, this is the first example of the use of the CYC6 or CAH1 promoters to perform a chemically regulated complementation of a Chlamydomonas mutant. Based on our data, the CYC6 and CAH1 promoters should be capable of fully complementing mutants in genes whose products exert their biological activity at low concentrations.

  6. Developmental regulation of aromatase activity in the rat hypothalamus

    International Nuclear Information System (INIS)

    Lephart, E.D.

    1989-01-01

    The brain of all mammalian species studied thus far contain an enzymatic activity (aromatase) that catalyzes the conversion of androgens to estrogens. The activity is highest during prenatal development and contributes to the establishment of sex differences which determine adult gonadotropin secretion patterns and reproductive behavior. The studies presented in this dissertation represent a systematic effort to elucidate the mechanism(s) that control the initiation of and contribute to maintaining rat hypothalamic aromatase activity during pre- and postnatal development. Aromatase enzyme activity was measured by the 3 H 2 O release assay or by traditional estrogen product isolation. Brain aromatase mRNA was detected by hybridization to a cDNA encoding rat aromatase cytochrome P-450. In both males and females the time of puberty was associated with a decline in hypothalamic aromatase activity. This decline may represent a factor underlying the peri-pubertal decrease in the sensitivity to gonadal steroid feedback that accompanies completion of puberty. The results also indicate that androgens regulate brain aromatase levels during both the prepubertal and peri-pubertal stages of sexual development and that this regulation is transiently lost in young adults. Utilizing a hypothalamic organotypic culture system, aromatase activity in vitro was maintained for as long as two days. The results of studies of a variety of hormonal and metabolic regulators suggest that prenatal aromatase activity is regulated by factor(s) that function independently from the classical cyclic AMP and protein kinase C trans-membrane signaling pathways

  7. Investigation on the Metabolic Regulation of pgi gene knockout Escherichia coli by Enzyme Activities and Intracellular Metabolite Concentrations

    Directory of Open Access Journals (Sweden)

    Nor ‘Aini, A. R.

    2006-01-01

    Full Text Available An integrated analysis of the cell growth characteristics, enzyme activities, intracellular metabolite concentrations was made to investigate the metabolic regulation of pgi gene knockout Escherichia coli based on batch culture and continuous culture which was performed at the dilution rate of 0.2h-1. The enzymatic study identified that pathways of pentose phosphate, ED pathway and glyoxylate shunt were all active in pgi mutant. The glycolysis enzymes i.e glyceraldehyde-3-phosphate dehydrogenase, fructose diphosphatase, pyruvate kinase, triose phosphate isomerase were down regulated implying that the inactivation of pgi gene reduced the carbon flux through glycolytic pathway. Meanwhile, the pentose phosphate pathway was active as a major route for intermediary carbohydrate metabolism instead of glycolysis. The pentose phosphate pathway generates most of the major reducing co-factor NADPH as shown by the increased of NADPH/NADP+ ratio in the mutant when compared with the parent strain. The fermentative enzymes such as acetate kinase and lactate dehydrogenase were down regulated in the mutant. Knockout of pgi gene results in the significant increase in the intracellular concentration of glucose-6-phosphate and decrease in the concentration of oxaloacetate. The slow growth rate of the mutant was assumed to be affected by the accumulation of glucose-6-phosphate and imbalance of NADPH reoxidation.

  8. Learning from co-housing initiatives — Between Passivhaus engineers and active inhabitants

    Directory of Open Access Journals (Sweden)

    Lidewij Chantal Tummers

    2017-10-01

    Full Text Available Following the UN world summits on Climate Change (Paris 2015 and Habitat (Quito 2016, most European cities assume an active role to implement internationally agreed goals related to climate change, translated in the so-called New Urban Agenda. At the same time, the urban housing market is increasingly inaccessible for low- and middle-income households. To overcome problems such as failing housing supply and high energy-bills, groups of residents take initiatives to create and manage housing projects collectively; these initiatives are further indicated as ‘co-housing’.  The aim of this study is to create deeper understanding of the current rise of co-housing in Europe, and what it could mean in urban policies addressing energy transition and climate change. There are two domains where co-housing can become an important asset for urban development: design and maintenance of (semi-public space for climate change mitigation, and the transition to a circular metabolism in housing. Based on empirical data, this thesis concludes that co-housing projects present relevant models and approaches for reducing the energy consumption and for integrating renewable energies in the general housing stock. Engineers can learn from co-housing pioneers to advance the targets for energy-transition and further develop sustainable cities. The thesis contributes to the emerging body of knowledge with a new understanding of co-housing, analysing its ‘key-features’ with an interdisciplinary framework, in a European context. It adds a new perspective to existing co-housing research, which is dominated by social sciences, by drawing attention to the physical characteristics of co-housing, produced in architectural, planning and engineering processes (the technosphere. The choices made during design and building are not only shaped by the residents’ aims and perception of sustainability, but also influenced by technosphere-related institutions, such as the

  9. Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex.

    Science.gov (United States)

    Wu, Rui; Kausar, Hina; Johnson, Paul; Montoya-Durango, Diego E; Merchant, Michael; Rane, Madhavi J

    2007-07-27

    We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK-activated protein kinase-2 (MK2), and heat shock protein 27 (Hsp27) and MK2 phosphorylates Akt on Ser-473. Additionally, dissociation of Hsp27 from Akt, prior to Akt activation, induced polymorphonuclear leukocyte (PMN) apoptosis. However, the role of Hsp27 in regulating Akt activation was not examined. This study tested the hypothesis that Hsp27 regulates Akt activation and promotes cell survival by scaffolding MK2 to the Akt signal complex. Here we show that loss of Akt/Hsp27 interaction by anti-Hsp27 antibody treatment resulted in loss of Akt/MK2 interaction, loss of Akt-Ser-473 phosphorylation, and induced PMN apoptosis. Transfection of myristoylated Akt (AktCA) in HK-11 cells induced Akt-Ser-473 phosphorylation, activation, and Hsp27-Ser-82 phosphorylation. Cotransfection of AktCA with Hsp27 short interfering RNA, but not scrambled short interfering RNA, silenced Hsp27 expression, without altering Akt expression in HK-11 cells. Silencing Hsp27 expression inhibited Akt/MK2 interaction, inhibited Akt phosphorylation and Akt activation, and induced HK-11 cell death. Deletion mutagenesis studies identified acidic linker region (amino acids 117-128) on Akt as an Hsp27 binding region. Deletion of amino acids 117-128 on Akt resulted in loss of its interaction with Hsp27 and MK2 but not with Hsp90 as demonstrated by immunoprecipitation and glutathione S-transferase pulldown studies. Co-transfection studies demonstrated that constitutively active MK2 (MK2EE) phosphorylated Aktwt (wild type) on Ser-473 but failed to phosphorylate Akt(Delta117-128) mutant in transfixed cells. These studies collectively define a novel role of Hsp27 in regulating Akt activation and cellular apoptosis by mediating interaction between Akt and its upstream activator MK2.

  10. Co-ordinate regulation of growth factor receptors and lipid phosphate phosphatase-1 controls cell activation by exogenous lysophosphatidate.

    Science.gov (United States)

    Pilquil, C; Ling, Z C; Singh, I; Buri, K; Zhang, Q X; Brindley, D N

    2001-11-01

    The serum-derived lipid growth factors, lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P), activate cells selectively through different members of a family of endothelial differentiation gene (EDG) receptors. Activation of EDG receptors by LPA and S1P provides a variety of signalling cascades depending upon the G-protein coupling of the different EDG receptors. This leads to chemotactic and mitogenic responses, which are important in wound healing. For example, LPA stimulates fibroblast division and S1P stimulates the chemotaxis and division of endothelial cells leading to angiogenesis. Counteracting these effects of LPA and S1P, are the actions of lipid phosphate phosphatases (LPP, or phosphatidate phosphohydrolases, Type 2). The isoform LPP-1 is expressed in the plasma membrane with its active site outside the cell. This enzyme is responsible for 'ecto-phosphatase' activity leading to the degradation of exogenous lipid phosphate mediators, particularly LPA. Expression of LPP-1 decreases cell activation by exogenous LPA. The mechanism for this is controversial and several mechanisms have been proposed. Evidence will be presented that the LPPs cross-talk with EDG and other growth factor receptors, thus, regulating the responses of the cells to lipid phosphate mediators of signal transduction.

  11. Regulation of brain aromatase activity in rats

    International Nuclear Information System (INIS)

    Roselli, C.E.; Ellinwood, W.E.; Resko, J.A.

    1984-01-01

    The distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of 3 H 2 O formed during the conversion of [1 beta- 3 H]androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. The greatest amount of aromatase activity was found in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA, but not in the amygdala or cerebral cortex. The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities to levels approximating those found in HPOA from intact males. Therefore, the results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats

  12. How is AMPK activity regulated in skeletal muscles during exercise?

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    AMPK is a metabolic "master" controller activated in skeletal muscle by exercise in a time and intensity dependent manner, and has been implicated in regulating metabolic pathways in muscle during physical exercise. AMPK signaling in skeletal muscle is regulated by several systemic...... and intracellular factors and the regulation of skeletal muscle AMPK in response to exercise is the focus of this review. Specifically, the role of LKB1 and phosphatase PP2C in nucleotide-dependent activation of AMPK, and ionized calcium in CaMKK-dependent activation of AMPK in working muscle is discussed. We also...

  13. Catalytic activity of Co/SiO2 and Co/TiO2 nanosized systems in the oxidation of carbon monoxide

    Science.gov (United States)

    Kelyp, A. A.; Smirnova, N. P.; Oleksenko, L. P.; Lutsenko, L. V.; Oranskaya, E. I.; Ripko, A. P.

    2013-06-01

    The effects of the preparation procedure, active component concentration, and conditions of formation of nanosized cobalt-containing systems based on TiO2 and SiO2 mesoporous powders on their catalytic activity in the oxidation of carbon monoxide were studied. The active phase in the systems was cobalt spinel CoCo2O4 found in all samples. High catalytic activity was found in the samples characterized by relatively high contents of surface active centers (cobalt cations with octahedral surroundings).

  14. Integrated co-regulation of bacterial arsenic and phosphorus metabolisms.

    Science.gov (United States)

    Kang, Yoon-Suk; Heinemann, Joshua; Bothner, Brian; Rensing, Christopher; McDermott, Timothy R

    2012-12-01

    Arsenic ranks first on the US Environmental Protection Agency Superfund List of Hazardous Substances. Its mobility and toxicity depend upon chemical speciation, which is significantly driven by microbial redox transformations. Genome sequence-enabled surveys reveal that in many microorganisms genes essential to arsenite (AsIII) oxidation are located immediately adjacent to genes coding for functions associated with phosphorus (Pi) acquisition, implying some type of functional importance to the metabolism of As, Pi or both. We extensively document how expression of genes key to AsIII oxidation and the Pi stress response are intricately co-regulated in the soil bacterium Agrobacterium tumefaciens. These observations significantly expand our understanding of how environmental factors influence microbial AsIII metabolism and contribute to the current discussion of As and P metabolism in the microbial cell. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  15. Graphene quantum dots /LaCoO3/attapulgite heterojunction photocatalysts with improved photocatalytic activity

    International Nuclear Information System (INIS)

    Zhu, Wei; Li, Xiazhang

    2017-01-01

    A new nanocomposite of graphene quantum dots/LaCoO 3 /attapulgite (GQDs/LaCoO 3 /ATP) was prepared by a facile impregnation method and was applied to degradation of the organic pollutants as photocatalyst under visible light irradiation. Multiple techniques were used to characterize the structures, morphologies and photocatalytic activities of samples. The photocatalytic activity of the GQDs/LaCoO 3 /ATP nanocomposites was effectively evaluated using Methylene blue (MB), antibiotic agent chlortetracycline (CHL) and tetracycline hydrochloride (TC). The as-synthesized GQDs/LaCoO 3 /ATP nanocomposites exhibited higher photocatalytic activities than LaCoO 3 /ATP, which showed a broad spectrum of photocatalytic degradation activity. The results of ESR and free radicals trapping experiments indicated that circle OH and h + were the main species for the photocatalytic degradation. GQDs played a significant role in the photocatalytic activity improvement of LaCoO 3 /ATP, increasing the visible light absorption, slowing the recombination and improving the charge transfer. (orig.)

  16. Graphene quantum dots /LaCoO3/attapulgite heterojunction photocatalysts with improved photocatalytic activity

    Science.gov (United States)

    Zhu, Wei; Li, Xiazhang

    2017-04-01

    A new nanocomposite of graphene quantum dots/LaCoO3/attapulgite (GQDs/LaCoO3/ATP) was prepared by a facile impregnation method and was applied to degradation of the organic pollutants as photocatalyst under visible light irradiation. Multiple techniques were used to characterize the structures, morphologies and photocatalytic activities of samples. The photocatalytic activity of the GQDs/LaCoO3/ATP nanocomposites was effectively evaluated using Methylene blue (MB), antibiotic agent chlortetracycline (CHL) and tetracycline hydrochloride (TC). The as-synthesized GQDs/LaCoO3/ATP nanocomposites exhibited higher photocatalytic activities than LaCoO3/ATP, which showed a broad spectrum of photocatalytic degradation activity. The results of ESR and free radicals trapping experiments indicated that • OH and h+ were the main species for the photocatalytic degradation. GQDs played a significant role in the photocatalytic activity improvement of LaCoO3/ATP, increasing the visible light absorption, slowing the recombination and improving the charge transfer.

  17. DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Cohen, Stephen Michael

    2017-01-01

    /TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family...... deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor...

  18. Psidium guajava extract inhibits thymus and activation-regulated chemokine (TARC/CCL17) production in human keratinocytes by inducing heme oxygenase-1 and blocking NF-κB and STAT1 activation.

    Science.gov (United States)

    Han, Eun Hee; Hwang, Yong Pil; Choi, Jae Ho; Yang, Ji Hye; Seo, Jong Kwon; Chung, Young Chul; Jeong, Hye Gwang

    2011-09-01

    Psidium guajava (P. guajava) is a food and medicinal plant with antioxidant, anti-inflammatory, and anti-allergic activities that support its traditional uses. The aim of this study was to determine the effects of P. guajava ethyl acetate extract (PGEA) on atopic dermatitis and to investigate the possible mechanisms by which PGEA inhibits cytokine-induced Th2 chemokine expression in HaCaT human keratinocyte cells. We found that PGEA suppressed the IFN-γ/TNF-α-co-induced production of thymus and activation-regulated chemokine (TARC) protein and mRNA in HaCaT cells. Additionally, PGEA inhibited the TNF-α/IFN-γ-co-induced activation of NF-κB and STAT1 and increased the expression of heme oxygenase-1 (HO-1) protein and mRNA. HO-1 inhibitor enhanced the suppressive effects of PGEA on TNF-α/IFN-γ-co-induced TARC production and gene expression. Collectively, these data demonstrate that PGEA inhibits chemokine expression in keratinocytes by inducing HO-1 expression and it suggests a possible therapeutic application in atopic dermatitis and other inflammatory skin diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Src regulates the activity of SIRT2

    International Nuclear Information System (INIS)

    Choi, You Hee; Kim, Hangun; Lee, Sung Ho; Jin, Yun-Hye; Lee, Kwang Youl

    2014-01-01

    Highlights: • Src decreases the protein levels of Sirt2. • Src inhibitor and knockdown of Src increase the protein levels of Sirt2. • Src interacts with and phosphorylates Sirt2. • Src regulate the activity of Sirt2. - Abstract: SIRT2 is a mammalian member of the Sirtuin family of NAD + -dependent protein deacetylases. The tyrosine kinase Src is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. The function of SIRT2 is modulated by post-translational modifications; however, the precise molecular signaling mechanism of SIRT2 through interactions with c-Src has not yet been established. In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104. c-Src also showed the ability to regulate the deacetylation activity of SIRT2. Investigation on the phosphorylation of SIRT2 suggested that this was the method of c-Src-mediated SIRT2 regulation

  20. GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation

    Directory of Open Access Journals (Sweden)

    Li Wang

    2018-01-01

    Full Text Available Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF signaling pathway in early embryoid bodies (EBs. Gcn5−/− EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage. Genomic analyses identified seven genes as putative direct targets of GCN5 during early differentiation, four of which are cMYC targets. These findings established a link between GCN5 and the FGF signaling pathway and highlighted specific GCN5-MYC partnerships in gene regulation during early differentiation.

  1. Activated H-Ras regulates hematopoietic cell survival by modulating Survivin

    International Nuclear Information System (INIS)

    Fukuda, Seiji; Pelus, Louis M.

    2004-01-01

    Survivin expression and Ras activation are regulated by hematopoietic growth factors. We investigated whether activated Ras could circumvent growth factor-regulated Survivin expression and if a Ras/Survivin axis mediates growth factor independent survival and proliferation in hematopoietic cells. Survivin expression is up-regulated by IL-3 in Ba/F3 and CD34 + cells and inhibited by the Ras inhibitor, farnesylthiosalicylic acid. Over-expression of constitutively activated H-Ras (CA-Ras) in Ba/F3 cells blocked down-modulation of Survivin expression, G 0 /G 1 arrest, and apoptosis induced by IL-3 withdrawal, while dominant-negative (DN) H-Ras down-regulated Survivin. Survivin disruption by DN T34A Survivin blocked CA-Ras-induced IL-3-independent cell survival and proliferation; however, it did not affect CA-Ras-mediated enhancement of S-phase, indicating that the anti-apoptotic activity of CA-Ras is Survivin dependent while its S-phase enhancing effect is not. These results indicate that CA-Ras modulates Survivin expression independent of hematopoietic growth factors and that a CA-Ras/Survivin axis regulates survival and proliferation of transformed hematopoietic cells

  2. Active Power Regulation based on Droop for AC Microgrid

    DEFF Research Database (Denmark)

    Li, Chendan; Coelho, Ernane A. A.; Firoozabadi, Mehdi Savaghebi

    2015-01-01

    In this paper, two different control strategies are proposed to address the active power regulation issue in AC microgrids. The principle of power regulation in the droop controller is firstly introduced. Frequency scheduling and droop gain scheduling on top of droop control is proposed...... to successfully follow the active power command. The limitation of each method is discussed in term of small signal stability and light load sharing, respectively. Discussion on the effects of power command is also given. The simulation is carried out for both the strategies to verify the active power control...

  3. NOS CO-OPS Active Currents Data, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has surface Active Currents data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These raw data have not...

  4. Switchable CO2 electroreduction via engineering active phases of Pd nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Dunfeng Gao; Fan Yang; Shu Miao; Jianguo Wang; Guoxiong Wang; Xinhe Bao; Hu Zhou; Fan Cai; Dongniu Wang; Yongfeng Hu; Bei Jiang; Wen-Bin Cai; Xiaoqi Chen; Rui Si

    2017-01-01

    Active-phase engineering is regularly utilized to tune the selectivity of metal nanoparticles (NPs) in heterogeneous catalysis.However,the lack of understanding of the active phase in electrocatalysis has hampered the development of efficient catalysts for CO2 electroreduction.Herein,we report the systematic engineering of active phases of Pd NPs,which are exploited to select reaction pathways for CO2 electroreduction.In situ X-ray absorption spectroscopy,in situ attenuated total reflection-infrared spectroscopy,and density functional theory calculations suggest that the formation of a hydrogen-adsorbed Pd surface on a mixture of the α-and β-phases of a palladium-hydride core (α+β PdHx@PdHx) above-0.2 V (vs.a reversible hydrogen electrode) facilitates formate production via the HCOO* intermediate,whereas the formation of a metallic Pd surface on the β-phase Pd hydride core (β PdHx@Pd) below-0.5 V promotes CO production via the COOH* intermediate.The main product,which is either formate or CO,can be selectively produced with high Faradaic efficiencies (>90%) and mass activities in the potential window of 0.05 to-0.9 V with scalable application demonstration.

  5. Catalytic activity of bimetal-containing Co,Pd systems in the oxidation of carbon monoxide

    Science.gov (United States)

    Oleksenko, L. P.; Lutsenko, L. V.

    2013-02-01

    The catalytic activity of low-percentage Co,Pd systems on ZSM-5, ERI, SiO2, and Al2O3 supports in the oxidation of CO was studied. The activity of bimetal-containing catalysts was shown to depend on the nature of the catalyst and the amount and ratio of their active components. According to the results of thermoprogrammed reduction with H2 (H2 TPR) and X-ray photoelectron spectroscopy (XPS) data, the metals are distributed as isolated cations or Coδ+-O-Pdδ+ clusters with cobalt and palladium cations surrounded by off-lattice oxygen in Co,Pd systems. The 0.8% Co,0.5% Pd-ZSM-5 bimetal catalysts were found to be more active due to the presence of clusters.

  6. The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system

    Directory of Open Access Journals (Sweden)

    Wang Qin

    2012-12-01

    Full Text Available Abstract Background Previous in vivo studies have shown that mesenchymal stem cell (MSC transplantation significantly improves the condition of a number of autoimmune diseases including autoimmune cerebrospinal meningitis, multiple sclerosis, glomerulonephritis and systemic lupus erythematosus. Methods To investigate the immunoregulatory effect of stem cell transplantation, human umbilical cord MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs from patients with rheumatoid arthritis (RA. Orphan nuclear receptor gamma (ROR-γ mRNA and protein expression was detected with real-time PCR and Western blotting. Interleukin (IL-17, IL-6 and tumor necrosis factor (TNF-α in the cell culture supernatant were measured using a flow cytometric bead capture method. Results After 72 hours of co-culture, the mRNA and protein expression levels of ROR-γ in co-cultured PBMCs were decreased compared with that in PBMC of RA patients cultured alone (p  Conclusions In vitro co-culture with MSCs down-regulated the inflammatory response of PBMCs from RA patients with severe disease activity, but had no significant effect on PBMCs from healthy controls or patients with mild disease activity, suggesting that the immunoregulatory role of MSCs may associate with the occurrence of inflammatory mediators.

  7. Nanostructured CoP: An efficient catalyst for degradation of organic pollutants by activating peroxymonosulfate

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Rui; Liu, Chao; Li, Jiansheng, E-mail: lijsh@mail.njust.edu.cn; Wang, Jing; Hu, Xingru; Sun, Xiuyun; Shen, Jinyou; Han, Weiqing; Wang, Lianjun

    2017-05-05

    Highlights: • The CoP/PMS system was first presented for decomposition of pollutants. • CoP exhibited dramatic catalytic activity. • Broadened pH range and favorable anti-interference of anions were achieved. • A possible mechanism for activation of PMS by CoP was proposed. - Abstract: A new catalyst system of CoP/peroxymonosulfate (PMS) is presented, which achieved significant improvement in catalytic activity. Nanostructured CoP, obtained by a simple solid-state reaction, exhibited dramatic catalytic activity with 97.2% degradation of orange II of 100 ppm within 4 min. Moreover, the high efficiency could be reached for other phenolic pollutants, i.e., phenol and 4-chlorophenol. The reaction rate is much higher than the most reported catalysts. Effect of parameters on catalytic activity of the catalyst was studied in detail. Notably, initial pH of the solution had a slight negative effect on the catalytic performance over the pH range 4.07–10.92, suggesting that CoP has the great adaptability of pH. CoP/PMS demonstrated excellent anti-interference performance toward anions (Cl{sup −}, NO{sub 3}{sup −}, and HCO{sub 3}{sup −}). In addition, the pathway of degradation of orange II is proposed by analyzing its intermediates. Based on the XPS spectra of CoP, the identification of the reactive species (·OH and SO{sub 4}·{sup −}) by electron paramagnetic resonance (EPR) analysis and quenching tests, a possible mechanism for activation of PMS by CoP was proposed. Considering the dramatic catalytic activity, a wide range of pH catalyst suited, CoP is believed to provide robust support for the promising industrial application of AOPs.

  8. Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

    Science.gov (United States)

    Caldo, Kristian Mark P; Acedo, Jeella Z; Panigrahi, Rashmi; Vederas, John C; Weselake, Randall J; Lemieux, M Joanne

    2017-10-01

    Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT1 1-113 ) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an α-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

  9. Trends in the Catalytic CO Oxidation Activity of Nanoparticles

    DEFF Research Database (Denmark)

    Nørskov, Jens Kehlet; Falsig, Hanne; Larsen, Britt Hvolbæk

    2008-01-01

    Going for gold: Density functional calculations show how gold nanoparticles are more active catalysts for CO oxidation than other metal nanoparticles. The high catalytic activity of nanosized gold clusters at low temperature is found to be related to the ability of low-coordinate metal atoms...

  10. Calmodulin-mediated activation of Akt regulates survival of c-Myc-overexpressing mouse mammary carcinoma cells.

    Science.gov (United States)

    Deb, Tushar B; Coticchia, Christine M; Dickson, Robert B

    2004-09-10

    c-Myc-overexpressing mammary epithelial cells are proapoptotic; their survival is strongly promoted by epidermal growth factor (EGF). We now demonstrate that EGF-induced Akt activation and survival in transgenic mouse mammary tumor virus-c-Myc mouse mammary carcinoma cells are both calcium/calmodulin-dependent. Akt activation is abolished by the phospholipase C-gamma inhibitor U-73122, by the intracellular calcium chelator BAPTA-AM, and by the specific calmodulin antagonist W-7. These results implicate calcium/calmodulin in the activation of Akt in these cells. In addition, Akt activation by serum and insulin is also inhibited by W-7. EGF-induced and calcium/calmodulin-mediated Akt activation occurs in both tumorigenic and non-tumorigenic mouse and human mammary epithelial cells, independent of their overexpression of c-Myc. These results imply that calcium/calmodulin may be a common regulator of Akt activation, irrespective of upstream receptor activator, mammalian species, and transformation status in mammary epithelial cells. However, only c-Myc-overexpressing mouse mammary carcinoma cells (but not normal mouse mammary epithelial cells) undergo apoptosis in the presence of the calmodulin antagonist W-7, indicating the vital selective role of calmodulin for survival of these cells. Calcium/calmodulin-regulated Akt activation is mediated directly by neither calmodulin kinases nor phosphatidylinositol 3-kinase (PI-3 kinase). Pharmacological inhibitors of calmodulin kinase kinase and calmodulin kinases II and III do not inhibit EGF-induced Akt activation, and calmodulin antagonist W-7 does not inhibit phosphotyrosine-associated PI-3 kinase activation. Akt is, however, co-immunoprecipitated with calmodulin in an EGF-dependent manner, which is inhibited by calmodulin antagonist W-7. We conclude that calmodulin may serve a vital regulatory function to direct the localization of Akt to the plasma membrane for its activation by PI-3 kinase.

  11. A co-expression gene network associated with developmental regulation of apple fruit acidity.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Xu, Kenong

    2015-08-01

    Apple fruit acidity, which affects the fruit's overall taste and flavor to a large extent, is primarily determined by the concentration of malic acid. Previous studies demonstrated that the major QTL malic acid (Ma) on chromosome 16 is largely responsible for fruit acidity variations in apple. Recent advances suggested that a natural mutation that gives rise to a premature stop codon in one of the two aluminum-activated malate transporter (ALMT)-like genes (called Ma1) is the genetic causal element underlying Ma. However, the natural mutation does not explain the developmental changes of fruit malate levels in a given genotype. Using RNA-seq data from the fruit of 'Golden Delicious' taken at 14 developmental stages from 1 week after full-bloom (WAF01) to harvest (WAF20), we characterized their transcriptomes in groups of high (12.2 ± 1.6 mg/g fw, WAF03-WAF08), mid (7.4 ± 0.5 mg/g fw, WAF01-WAF02 and WAF10-WAF14) and low (5.4 ± 0.4 mg/g fw, WAF16-WAF20) malate concentrations. Detailed analyses showed that a set of 3,066 genes (including Ma1) were expressed not only differentially (P FDR < 0.05) between the high and low malate groups (or between the early and late developmental stages) but also in significant (P < 0.05) correlation with malate concentrations. The 3,066 genes fell in 648 MapMan (sub-) bins or functional classes, and 19 of them were significantly (P FDR < 0.05) co-enriched or co-suppressed in a malate dependent manner. Network inferring using the 363 genes encompassed in the 19 (sub-) bins, identified a major co-expression network of 239 genes. Since the 239 genes were also differentially expressed between the early (WAF03-WAF08) and late (WAF16-WAF20) developmental stages, the major network was considered to be associated with developmental regulation of apple fruit acidity in 'Golden Delicious'.

  12. Active Learning and Self-Regulation Enhance Student Teachers’ Professional Competences

    OpenAIRE

    Virtanen, Päivi; Niemi, Hannele M.; Nevgi, Anne

    2017-01-01

    The study identifies the relationships between active learning, student teachers’ self-regulated learning and professional competences. Further, the aim is to investigate how active learning promotes professional competences of student teachers with different self-regulation profiles. Responses from 422 student teachers to an electronic survey were analysed using statistical methods. It was found that the use of active learning methods, such as goal-oriented and intentional learning as well a...

  13. BTG2 is an LXXLL-dependent co-repressor for androgen receptor transcriptional activity

    International Nuclear Information System (INIS)

    Hu, Xu-Dong; Meng, Qing-Hui; Xu, Jia-Ying; Jiao, Yang; Ge, Chun-Min; Jacob, Asha; Wang, Ping; Rosen, Eliot M; Fan, Saijun

    2011-01-01

    Research highlights: → BTG2 associates with AR, androgen causes an increase of the interaction. → BTG2 as a co-repressor inhibits the AR-mediated transcription activity. → BTG2 inhibits the transcription activity and expression of PSA. → An intact 92 LxxLL 96 motif is essential and necessary for these activities of BTG2, while the 20 LxxLL 24 motif is not required. → Ectopic expression of BTG2 reduces proliferation of prostate cancer cells. -- Abstract: The tumor suppressor gene, BTG2 has been down-regulated in prostate cancer and the ectopic expression of this gene has been shown to inhibit prostate cancer cell growth. Sequence analysis revealed that the BTG2 protein contains two leucine-rich motifs ( 20 LxxLL 24 and 92 LxxLL 96 ), which are usually found in nuclear receptor co-factors. Based on this, we postulated that there will be an association between BTG2 and AR. In this study, we discovered that BTG2 directly bound to the androgen receptor (AR) in the absence of 5α-dihydrotestosterone (DHT), and in the presence of the androgen, this interaction was increased. BTG2 bearing the mutant 20 LxxLL 24 motif bound to AR equally efficient as the wild-type BTG2, while BTG2 bearing the mutant 92 LxxLL 96 motif failed to interact with AR. Functional studies indicated that ectopic expression of BTG2 caused a significant inhibition of AR-mediated transcriptional activity and a decreased growth of prostate cancer cells. Androgen-induced promoter activation and expression of prostate-specific antigen (PSA) are significantly attenuated by BTG2. The intact 92 LxxLL 96 motif is required for these activities. These findings, for the first time, demonstrate that BTG2 complexes with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway.

  14. BTG2 is an LXXLL-dependent co-repressor for androgen receptor transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xu-Dong [School of Radiation Medicine and Public Health, Medical College of Soochow University, Suzhou 215123 (China); Meng, Qing-Hui [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 (United States); Xu, Jia-Ying; Jiao, Yang [School of Radiation Medicine and Public Health, Medical College of Soochow University, Suzhou 215123 (China); Ge, Chun-Min [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 (United States); Jacob, Asha; Wang, Ping [North Shore University Hospital-Long Island Jewish Medical Center and The Feinstein Institute for Medical Research, Manhasset, NY 11030 (United States); Rosen, Eliot M [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057 (United States); Fan, Saijun, E-mail: sjfan@suda.edu.cn [School of Radiation Medicine and Public Health, Medical College of Soochow University, Suzhou 215123 (China)

    2011-01-28

    Research highlights: {yields} BTG2 associates with AR, androgen causes an increase of the interaction. {yields} BTG2 as a co-repressor inhibits the AR-mediated transcription activity. {yields} BTG2 inhibits the transcription activity and expression of PSA. {yields} An intact {sup 92}LxxLL{sup 96} motif is essential and necessary for these activities of BTG2, while the {sup 20}LxxLL{sup 24} motif is not required. {yields} Ectopic expression of BTG2 reduces proliferation of prostate cancer cells. -- Abstract: The tumor suppressor gene, BTG2 has been down-regulated in prostate cancer and the ectopic expression of this gene has been shown to inhibit prostate cancer cell growth. Sequence analysis revealed that the BTG2 protein contains two leucine-rich motifs ({sup 20}LxxLL{sup 24} and {sup 92}LxxLL{sup 96}), which are usually found in nuclear receptor co-factors. Based on this, we postulated that there will be an association between BTG2 and AR. In this study, we discovered that BTG2 directly bound to the androgen receptor (AR) in the absence of 5{alpha}-dihydrotestosterone (DHT), and in the presence of the androgen, this interaction was increased. BTG2 bearing the mutant {sup 20}LxxLL{sup 24} motif bound to AR equally efficient as the wild-type BTG2, while BTG2 bearing the mutant {sup 92}LxxLL{sup 96} motif failed to interact with AR. Functional studies indicated that ectopic expression of BTG2 caused a significant inhibition of AR-mediated transcriptional activity and a decreased growth of prostate cancer cells. Androgen-induced promoter activation and expression of prostate-specific antigen (PSA) are significantly attenuated by BTG2. The intact {sup 92}LxxLL{sup 96} motif is required for these activities. These findings, for the first time, demonstrate that BTG2 complexes with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway.

  15. Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice

    Directory of Open Access Journals (Sweden)

    Jiesi Wang

    2017-05-01

    Full Text Available The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na+-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility. In vivo and in vitro experiments revealed that upregulation of ASCT2 expression in CSDS was regulated through histone hyper-acetylation, not DNA methylation in its promoter region. Immunohistochemistry demonstrated the co-localization of ASCT2 and D-serine. Uptake of D-serine by ASCT2 was demonstrated by in vivo and in vitro experiments. Our results indicate that CSDS induces ASCT2 expression through epigenetic activation and decreases hippocampal D-serine levels, leading to social avoidance, and immobility. Thus, targeting D-serine transport represents an attractive new strategy for treating depression.

  16. Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice.

    Science.gov (United States)

    Xiao, Chun; Wu, Qingping; Zhang, Jumei; Xie, Yizhen; Cai, Wen; Tan, Jianbin

    2017-01-20

    Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action. Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC-MS spectroscopy, RESULTS: F31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin. Data suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These

  17. Properties of latent and thiol-activated rat hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase and regulation of enzyme activity.

    Science.gov (United States)

    Dotan, I; Shechter, I

    1983-10-15

    The effect of the thiols glutathione (GSH), dithiothreitol (DTT), and dithioerythritol (DTE) on the conversion of an inactive, latent form (El) of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) to a catalyticaly active form (Ea) is examined. Latent hepatic microsomal HMG-CoA reductase is activated to a similar degree of activation by DTT and DTE and to a lower extent by GSH. All three thiols affect both Km and Vmax values of the enzyme toward HMG-CoA and NADPH. Studies of the effect of DTT on the affinity binding of HMG-CoA reductase to agarose-hexane-HMG-CoA (AG-HMG-CoA) resin shows that thiols are necessary for the binding of the enzyme to the resin. Removal of DTT from AG-HMG-CoA-bound soluble Ea (active enzyme) does not cause dissociation of the enzyme from the resin at low salt concentrations. Substitution of DTT by NADPH does not promote binding of soluble El (latent enzyme) to AG-HMG-CoA. The enzymatic activity of Ea in the presence of DTT and GSH indicates that these thiols compete for the same binding site on the enzyme. Diethylene glycol disulfide (ESSE) and glutathione disulfide (GSSG) inhibit the activity of Ea. ESSE is more effective for the inhibition of Ea than GSSG, causing a higher degree of maximal inhibition and affecting the enzymatic activity at lower concentrations. A method is described for the rapid conversion of soluble purified Ea to El using gel-filtration chromatography on Bio-Gel P-4 columns. These combined results point to the importance of the thiol/disulfide ratio for the modulation of hepatic HMG-CoA reductase activity.

  18. Simulated shift work in rats perturbs multiscale regulation of locomotor activity

    Science.gov (United States)

    Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A. J. L.; Shea, Steven A.; Buijs, Ruud M.; Hu, Kun

    2014-01-01

    Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation. PMID:24829282

  19. Long-chain acyl-CoA-dependent regulation of gene expression in bacteria, yeast and mammals

    DEFF Research Database (Denmark)

    Black, P N; Færgeman, Nils J.; DiRusso, C C

    2000-01-01

    ). Both repression and activation are dependent upon the function of either of the acyl-CoA synthetases Faa1p or Faa4p. In mammals, purified hepatocyte nuclear transcription factor 4alpha (HNF-4alpha) like E. coli FadR, binds long chain acyl-CoA directly. Coexpression of HNF-4alpha and acyl-CoA synthetase...

  20. Evaluation of handling and reuse approaches for the waste generated from MEA-based CO2 capture with the consideration of regulations in the UAE.

    Science.gov (United States)

    Nurrokhmah, Laila; Mezher, Toufic; Abu-Zahra, Mohammad R M

    2013-01-01

    A waste slip-stream is generated from the reclaiming process of monoethanolamine (MEA) based Post-Combustion Capture (PCC). It mainly consists of MEA itself, ammonium, heat-stable salts (HSS), carbamate polymers, and water. In this study, the waste quantity and nature are characterized for Fluor's Econamine FGSM coal-fired CO2 capture base case. Waste management options, including reuse, recycling, treatment, and disposal, are investigated due to the need for a more environmentally sound handling. Regulations, economic potential, and associated costs are also evaluated. The technical, economic, and regulation assessment suggests waste reuse for NOx scrubbing. Moreover, a high thermal condition is deemed as an effective technique for waste destruction, leading to considerations of waste recycling into a coal burner or incineration. As a means of treatment, three secondary-biological processes covering Complete-Mix Activated Sludge (CMAS), oxidation ditch, and trickling filter are designed to meet the wastewater standards in the United Arab Emirates (UAE). From the economic point of view, the value of waste as a NOx scrubbing agent is 6,561,600-7,348,992 USD/year. The secondary-biological treatment cost is 0.017-0.02 USD/ton of CO2, while the cost of an on-site incinerator is 0.031 USD/ton of CO2 captured. In conclusion, secondary biological treatment is found to be the most economical option.

  1. Plant Signals Disrupt (regulate?) Arbuscular Mycorrhizal Fungal Growth Under Enhanced Ozone and CO2 Growing Conditions for Populus tremuloides

    Science.gov (United States)

    Miller, R. M.; Podila, G. K.

    2008-12-01

    evaluating microarray data of more than 2300 genes that are regulated (out of 25,000) in aspen mycorrhizal roots, the eCO2 responsive and eO3 tolerant aspen ecotype 271 demonstrated upregulation for antioxidant genes under eCO2+eO3 conditions. We found decreased expression of both neutral and acid invertase genes indicating that the availability of carbohydrate to the fungus is reduced. We also found an increase in plant amino acid transporters under eO3 and eCO2+eO3 that partitions more nitrogen to the plant from mycorrhizal roots and triggers the fungus into an N-starvation and lipid storage mode. This observation is supported by down-regulation of genes involved in nitrogen utilization in Glomus and the enrichment of hyphal 15N content, as well as an increase in the AMF marker storage lipid (neutral fatty acid 16:1w5c)in the root. The up-regulation of pathways involved in the formation of triglycerides that can be taken up by the fungus may be a critical step for changes in Glomus lipid metabolism. Also, in support of the above findings, is the rather high expression of genes involved in iron sequestration by aspen clone 271 when exposed to both eO3 and eCO2+eO3 fumigation. Iron is needed for both fatty acid (FA) desaturases and fatty acid synthase. Under eCO2+eO3, we found down-regulation of FA desaturases in Glomus, suggesting reduced levels of iron could be a potential signal for the fungus to go into storage mode and reduced growth of extraradical hyphae into the soil.

  2. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  3. Preparation of granular activated carbons from yellow mombin fruit stones for CO2 adsorption.

    Science.gov (United States)

    Fiuza, Raildo Alves; Medeiros de Jesus Neto, Raimundo; Correia, Laise Bacelar; Carvalho Andrade, Heloysa Martins

    2015-09-15

    Stones of yellow mombin, a native fruit of the tropical America and West Indies, were used as starting materials to produce activated carbons, subsequently used as adsorbent for CO2 capture. The carbonaceous materials were either chemically activated with HNO3, H3PO4 and KOH or physically activated with CO2. The carbon samples were characterized by SEM, EDX, TG/DTA, Raman spectroscopy, physical adsorption for textural analysis and by acid-base titrations. The CO2 adsorption capacity and adsorption cycles were investigated by TG. The results indicate that the capacity of CO2 adsorption may be maximized on highly basic surfaces of micropores smaller than 1 nm. The KOH activated carbon showed high and stable capacity of CO2 adsorption after 10 cycles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Kindlins, integrin activation and the regulation of talin recruitment to αIIbβ3.

    Directory of Open Access Journals (Sweden)

    Bryan N Kahner

    Full Text Available Talins and kindlins bind to the integrin β3 cytoplasmic tail and both are required for effective activation of integrin αIIbβ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to β3 is sufficient to activate purified integrin αIIbβ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbβ3, full-length talin and kindlin recruitment to β3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbβ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbβ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbβ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the β3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbβ3, suggesting that they co-activate integrin through a mechanism independent of recruitment.

  5. PREPARATION AND CATALYTIC ACTIVITY FOR ISOPROPYL BENZENE CRACKING OF Co, Mo AND Co/Mo-Al2O3-PILLARED MONTMORILLONITE CATALYSTS

    Directory of Open Access Journals (Sweden)

    Hasanudin Hasanudin

    2010-06-01

    Full Text Available It has been prepared Co, Mo and Co/Mo-Al2O3-pillared montmorillonite catalysts using montmorillonite clay  as raw material. The structure and porosity of the catalysts were determined using N2 adsorption-desorption and FT-IR spectroscopy analysis methods. Isopropyl benzene cracking using these catalysts were used to test the catalytic activity and performance of Co, Mo and Co/Mo-Al2O3-pillared montmorillonites.  Characterization results showed that pillarization resulted in the increase of the total pore volume and specific surface area of the clay. Meanwhile, transition metals (Co, Mo and Co/Mo loaded on Al2O3-pillared monmorillonites could increase the catalytic activity of the catalysts for isopropyl benzene cracking significantly.   Keywords: pillared monmorillonite, isopropyl benzene  and cracking catalyst

  6. Granular bamboo-derived activated carbon for high CO(2) adsorption: the dominant role of narrow micropores.

    Science.gov (United States)

    Wei, Haoran; Deng, Shubo; Hu, Bingyin; Chen, Zhenhe; Wang, Bin; Huang, Jun; Yu, Gang

    2012-12-01

    Cost-effective biomass-derived activated carbons with a high CO(2) adsorption capacity are attractive for carbon capture. Bamboo was found to be a suitable precursor for activated carbon preparation through KOH activation. The bamboo size in the range of 10-200 mesh had little effect on CO(2) adsorption, whereas the KOH/C mass ratio and activation temperature had a significant impact on CO(2) adsorption. The bamboo-derived activated carbon had a high adsorption capacity and excellent selectivity for CO(2) , and also the adsorption process was highly reversible. The adsorbed amount of CO(2) on the granular activated carbon was up to 7.0 mmol g(-1) at 273 K and 1 bar, which was higher than almost all carbon materials. The pore characteristics of activated carbons responsible for high CO(2) adsorption were fully investigated. Based on the analysis of narrow micropore size distribution of several activated carbons prepared under different conditions, a more accurate micropore range contributing to CO(2) adsorption was proposed. The volume of micropores in the range of 0.33-0.82 nm had a good linear relationship with CO(2) adsorption at 273 K and 1 bar, and the narrow micropores of about 0.55 nm produced the major contribution, which could be used to evaluate CO(2) adsorption on activated carbons. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [Regulation of alternative CO{sub 2} fixation pathways in procaryotic and eucaryotic photosynthetic organisms]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-31

    The major goal of this project is to determine how microorganisms regulate the assimilation of CO{sup 2} via pathways alternative to the usual Calvin reductive pentose phosphate scheme. In particular, we are interest in the molecular basis for switches in CO{sub 2} metabolic paths. Several earlier studies had indicated that purple nonsulfur photosynthetic bacteria assimilate significant amounts of CO{sub 2} via alternative non-Calvin routes. We have deleted the gene that encodes. RubisCo (ribulose bisphosphate carboxylase/oxygenase) in both the Rhodobacter sphaeroids and Rhodospirillum rubrum. The R. sphaeroides RubisCO deletion strain (strain 16) could not grow under photoheterotrophic conditions with malate as electron donor and CO{sub 2} as the electron acceptor; however the R. rub RubisCO deletion strain (strain I-19) could. Over the past year we have sought to physiologically characterize strain 16PHC. We found that, 16PHC exhibited rates of whole-cell CO{sub 2} fixation which were significantly higher than strain 16. Strain 16PHC could not grow photolithoautotrophically in a CO{sub 2} atmosphere; however, CO{sub 2} fixation catalyzed by photoheterotrophically grown 16PHC was repressed by the addition of DMSO. Likewise, we found that cells initially grown in the presence of DMSO could induce the CO{sub 2} fixation system when DMSO was removed. Thus, these results suggested that both PHC and I-19 could be used to study alternative CO{sub 2} fixation reactions and their significance in R. sphaexoides and R. rubrum.

  8. Graphene and TiO_2 co-modified flower-like Bi_2O_2CO_3: A novel multi-heterojunction photocatalyst with enhanced photocatalytic activity

    International Nuclear Information System (INIS)

    Ao, Yanhui; Xu, Liya; Wang, Peifang; Wang, Chao; Hou, Jun; Qian, Jin; Li, Yi

    2015-01-01

    Graphical abstract: A novel multi-heterojunction photocatalyst (graphene and TiO_2 co-modified flower-like Bi_2O_2CO_3) was prepared for the first time. The as-obtained samples showed much higher activity compared to pure Bi_2O_2CO_3, TiO_2 and GR–Bi_2O_2CO_3 for dye degradation, which is almost 14 times higher than that of pure Bi_2O_2CO_3 and also much higher than the sum of graphene–Bi_2O_2CO_3 and TiO_2. - Highlights: • Graphene and TiO_2 co-modified flower-like Bi_2O_2CO_3 was prepared for the first time. • The sample shows enhanced photocatalytic activity due to the formation of multi-heterojunction. • The sample also exhibits a synergetic effect of graphene and TiO_2. • The composite photocatalyst shows a good stability for dye degradation. - Abstract: In this paper, graphene (GR) and titania co-modified flower-like Bi_2O_2CO_3 multi-heterojunction composite photocatalysts were prepared by a simple and feasible two step hydrothermal process. The prepared samples were analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM), transmission electron microscopy (TEM), UV–vis diffuse reflectance spectrometry (DRS), photoluminescence (PL), N_2 adsorption–desorption isotherm, and photo-induced current. The photocatalytic activity was investigated by the degradation of MO under UV light irradiation. The as prepared multi-heterojunction GR/Bi_2O_2CO_3/TiO_2 composites exhibited much higher photocatalytic activity than pure Bi_2O_2CO_3, TiO_2 and GR–Bi_2O_2CO_3. The higher performance of GR/Bi_2O_2CO_3/TiO_2 can be ascribed to the formation of multi-heterojunctions, which promote the effective separation of photo-induced electron–hole pairs. Moreover, the higher photocatalytic activity can also be ascribed to the high surface area of GR and TiO_2, which offers more active sites for the photodegradation reaction. Furthermore, the photocatalytic activity of GR/Bi_2O_2CO_3/TiO_2 remained without striking decrease after five cycles

  9. THE EUROPEAN MODEL OF STATE REGULATION OF TOURISM ACTIVITIES

    Directory of Open Access Journals (Sweden)

    О. Davydova

    2013-11-01

    Full Text Available In the article the existing model of state regulation of the development of tourism. Expediency of the European model of state regulation of tourism development in Ukraine. It is noted that the European model of state regulation of tourism activities based on the coordination of marketing activities and the development of cooperation between the public and private sectors. The basic forms of public-private partnerships and the advantages of using cluster model of development of tourism, namely, contracts, production sharing agreement, lease, joint venture. Promising areas of application of the PPP identified the transport sector, housing and utilities, energy and tourism sector. The features of cluster formations in the country and the prospects for tourism clusters.

  10. Preliminary evidences of CCM operation and its down regulation in relation to increasing CO2 levels in natural phytoplankton assemblages from the coastal waters of Bay of Bengal

    Science.gov (United States)

    Biswas, Haimanti; Rahman Shaik, Aziz Ur; Bandyopadhyay, Debasmita

    2014-05-01

    levels, CA activity was enhanced and accelerated DIC transport and photosynthetic rate. Moreover, δ13CPOM values of low CO2 samples (both Zn treated and untreated) were almost identical, though the rate of photosynthesis was higher in response to Zn addition. This could be because of the fact that under low CO2 levels, DIC was possibly transported as HCO3- and an active HCO3- transport can contribute to low discrimination of 13C compared to diffusive CO2uptake leading to unaltered values of δ13CPOM. Furthermore, under low CO2 treatments, the need of nitrogen resource can be higher to maintain an active CCM (to build-up required proteins, Rubisco and CCM components) and our results showed higher values of δ15NPOMunder low CO2 levels relative to the high CO2treatments suggesting higher nitrogen utilization efficiency in the former case. These observations strengthen the possibility of operating an active CCM under low CO2 levels. HPLC pigment analysis revealed the occurrences of diatoxanthin (DT) [indicator of non-photo-chemical quenching (NPQ)] and high values of photoprotective carotenoid to light harvesting carotenoid ratios (PPC/LHC) in the low CO2 treated cells indicating light stress. This is likely that, when CO2, the only substrate for Rubisco, is low, absorbed light energy within the cell can be surplus leading to photo-damage and to protect the cell from potential damage, DT was produced by energy dissipation via NPQ and PPC were synthesized in excess of LHC. Conversely, in Zn and high CO2 treated cells, the absence of DT and reduced values of PPC/LHC indirectly indicates reduced light stress which was possibly because of enhanced supply of Rubisco substrate either via active bicarbonate transport or diffusive CO2 supply. Thus, we infer that the diatom dominated phytoplankton communities from the study area perform CCMs under low CO2 conditions and the same can be down regulated upon the increasing levels of CO2 and the community may benefit from the

  11. Commission de regulation de l'energie. Activity Report June 2003

    International Nuclear Information System (INIS)

    2003-06-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the June 2003 activity report of CRE. Content: A - Energy markets regulation: a new step; B - Gas market regulation: gas markets and actors, gas market regulation (legal and institutional framework, networks access, methane terminals and modulation services, freedom spaces, European market regulation, gas utility, CRE gas activities and priorities in 2003); C - Electricity market regulation: electricity markets (European markets, operators activity on the French market), French electricity market regulation (public networks access, trans-border power exchanges, EDF's un-bundled accounts audit, market operation), electric utility in the regulated market (public utility content, public utility charges, power generation public utility financing, electricity pre-tax sale tariffs for non-eligible customers); D - CRE operation (means and resources, exercise of its implementing powers, European and international activities); E - Appendixes: Glossary; Units and conversions; Council of European Energy Regulators, Index of figures and tables

  12. Low pH induces co-ordinate regulation of gene expression in oesophageal cells.

    Science.gov (United States)

    Duggan, Shane P; Gallagher, William M; Fox, Edward J P; Abdel-Latif, Mohammed M; Reynolds, John V; Kelleher, Dermot

    2006-02-01

    The development of gastro-oesophageal reflux disease (GORD) is known to be a causative risk factor in the evolution of adenocarcinoma of the oesophagus. The major component of this reflux is gastric acid. However, the impact of low pH on gene expression has not been extensively studied in oesophageal cells. This study utilizes a transcriptomic and bioinformatic approach to assess regulation of gene expression in response to low pH. In more detail, oesophageal adenocarcinoma cell lines were exposed to a range of pH environments. Affymetrix microarrays were used for gene-expression analysis and results were validated using cycle limitation and real-time RT-PCR analysis, as well as northern and western blotting. Comparative promoter transcription factor binding site (TFBS) analysis (MatInspector) of hierarchically clustered gene-expression data was employed to identify the elements which may co-ordinately regulate individual gene clusters. Initial experiments demonstrated maximal induction of EGR1 gene expression at pH 6.5. Subsequent array experimentation revealed significant induction of gene expression from such functional categories as DNA damage response (EGR1-4, ATF3) and cell-cycle control (GADD34, GADD45, p57). Changes in expression of EGR1, EGR3, ATF3, MKP-1, FOSB, CTGF and CYR61 were verified in separate experiments and in a variety of oesophageal cell lines. TFBS analysis of promoters identified transcription factors that may co-ordinately regulate gene-expression clusters, Cluster 1: Oct-1, AP4R; Cluster 2: NF-kB, EGRF; Cluster 3: IKRS, AP-1F. Low pH has the ability to induce genes and pathways which can provide an environment suitable for the progression of malignancy. Further functional analysis of the genes and clusters identified in this low pH study is likely to lead to new insights into the pathogenesis and therapeutics of GORD and oesophageal cancer.

  13. Regulator and industry Co-operation on safety research: challenges and opportunities. Final report and answers to questionnaire

    International Nuclear Information System (INIS)

    2003-02-01

    A Group has been set up by the CSNI to identify and review the issues which hinder closer co-operation on research between regulators and industry, and to propose possible ways for resolving such issues while maintaining regulatory independence in decision-making. The Group has analyzed the potential advantages and disadvantages of regulator-industry collaboration in safety research and has also provided indications on how to overcome possible difficulties that can arise from such collaboration. The Group focused in particular on the issue of regulator independence, on means to preserve it and ways to demonstrate it to the public while undertaking collaboration with industry

  14. Optimization of Enzyme Co-Immobilization with Sodium Alginate and Glutaraldehyde-Activated Chitosan Beads.

    Science.gov (United States)

    Gür, Sinem Diken; İdil, Neslihan; Aksöz, Nilüfer

    2018-02-01

    In this study, two different materials-alginate and glutaraldehyde-activated chitosan beads-were used for the co-immobilization of α-amylase, protease, and pectinase. Firstly, optimization of multienzyme immobilization with Na alginate beads was carried out. Optimum Na alginate and CaCl 2 concentration were found to be 2.5% and 0.1 M, respectively, and optimal enzyme loading ratio was determined as 2:1:0.02 for pectinase, protease, and α-amylase, respectively. Next, the immobilization of multiple enzymes on glutaraldehyde-activated chitosan beads was optimized (3% chitosan concentration, 0.25% glutaraldehyde with 3 h of activation and 3 h of coupling time). While co-immobilization was successfully performed with both materials, the specific activities of enzymes were found to be higher for the enzymes co-immobilized with glutaraldehyde-activated chitosan beads. In this process, glutaraldehyde was acting as a spacer arm. SEM and FTIR were used for the characterization of activated chitosan beads. Moreover, pectinase and α-amylase enzymes immobilized with chitosan beads were also found to have higher activity than their free forms. Three different enzymes were co-immobilized with these two materials for the first time in this study.

  15. Deliberative democracy and co-management of natural resources: The case of Funäsdalen snowmobile regulation area

    Directory of Open Access Journals (Sweden)

    Anna Karin Elise Zachrisson

    2009-09-01

    Full Text Available The purpose of this article is to deepen the understanding of how co-management and deliberative democracy relate to one another. Deliberation is an understudied aspect of common-pool resource theory that could be developed by a closer connection to deliberative democratic theory. Co-management studies may also provide needed empirical insights to deliberative democratic theory. A framework is developed to analyze to what degree co-management arrangements incorporate deliberative elements. To test its usefulness, a case study of a co-management process in Sweden is analyzed. In Funäsdalsfjällen, a conflict-ridden situation caused by snowmobiles ended in agreement and the establishment of a municipal regulation area. Central and regional authorities initially failed to resolve the conflict, but when the municipality started working directly with the relevant interest groups, agreement was reached. Deliberative elements are shown central to the success, and it is concluded that co-management and deliberative democratic approaches indeed do cross-fertilize one another.

  16. AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Hwan; Choi, Soo-Youn; Kang, Byung-Hee; Lee, Soon-Min [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Hyung Soon; Kang, Gum-Yong; Bang, Joo Young [Center for Biomedical Mass Spectrometry, Diatech Korea Co., Ltd., Seoul (Korea, Republic of); Cho, Eun-Jung [National Research Laboratory for Chromatin Dynamics, College of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Youn, Hong-Duk, E-mail: hdyoun@snu.ac.kr [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence and Technology, Seoul National University, Seoul (Korea, Republic of)

    2013-02-01

    Highlights: ► AMPK phosphorylates CtBP1 on serine 158. ► AMPK-mediated phosphorylation of CtBP1 causes the ubiquitination and nuclear export of CtBP1. ► AMPK downregulates the CtBP1-mediated repression of Bax transcription. -- Abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.

  17. Cathodic electrochemical activation of Co3O4 nanoarrays: a smart strategy to significantly boost the hydrogen evolution activity.

    Science.gov (United States)

    Yang, Li; Zhou, Huang; Qin, Xin; Guo, Xiaodong; Cui, Guanwei; Asiri, Abdullah M; Sun, Xuping

    2018-02-22

    Co(hydro)oxides show unsatisfactory catalytic activity for the hydrogen evolution reaction (HER) in alkaline media, and it is thus highly desirable but still remains a challenge to design and develop Co(hydro)oxide derived materials as superb hydrogen-evolving catalysts using a facile, rapid and less energy-intensive method. Here, we propose a cathodic electrochemical activation strategy toward greatly boosted HER activity of a Co 3 O 4 nanoarray via room-temperature cathodic polarization in sodium hypophosphite solution. After activation, the overpotential significantly decreases from 260 to 73 mV to drive a geometrical catalytic current density of 10 mA cm -2 in 1.0 M KOH. Notably, this activated electrode also shows strong long-term electrochemical durability with the retention of its catalytic activity at 100 mA cm -2 for at least 40 h.

  18. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis by oxylanosterols

    Energy Technology Data Exchange (ETDEWEB)

    Panini, S.R.; Sexton, R.C.; Gupta, A.K.; Parish, E.J.; Chitrakorn, S.; Rudney, H.

    1986-11-01

    Treatment of rat intestinal epithelial cell cultures with the oxidosqualene cyclase inhibitor, 3 beta-(2-(diethylamino)-ethoxy)androst-5-en-17-one (U18666A), resulted in an accumulation of squalene 2,3:22,23-dioxide (SDO). When U18666A was withdrawn and the cells were treated with the sterol 14 alpha-demethylase inhibitor, ketoconazole, SDO was metabolized to a product identified as 24(S),25-epoxylanosterol. To test the biological effects and cellular metabolism of this compound, we prepared 24(RS),25-epoxylanosterol by chemical synthesis. The epimeric mixture of 24,25-epoxylanosterols could be resolved by high performance liquid chromatography on a wide-pore, non-endcapped, reverse phase column. Both epimers were effective suppressors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity of IEC-6 cells. The suppressive action of the natural epimer, 24(S),25-epoxylanosterol, but not that of 24(R),25-epoxylanosterol could be completely prevented by ketoconazole. IEC-6 cells could efficiently metabolize biosynthetic 24(S),25-epoxy(/sup 3/H)anosterol mainly to the known reductase-suppressor 24(S),25-epoxycholesterol. This metabolism was substantially reduced by ketoconazole. These data support the conclusion that 24(S),25-epoxylanosterol per se is not a suppressor of HMG-CoA reductase activity but is a precursor to a regulatory oxysterol(s). It has recently been reported that 25-hydroxycholesterol can occur naturally in cultured cells in amounts sufficient to effect regulation of HMG-CoA reductase. In order to investigate the biological effects of possible precursors of 25-hydroxycholesterol, we chemically synthesized 25-hydroxylanosterol and 25-hydroxylanostene-3-one. Both oxylanosterol derivatives suppressed cellular sterol synthesis at the level of HMG-CoA reductase. (Abstract Truncated)

  19. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis by oxylanosterols

    International Nuclear Information System (INIS)

    Panini, S.R.; Sexton, R.C.; Gupta, A.K.; Parish, E.J.; Chitrakorn, S.; Rudney, H.

    1986-01-01

    Treatment of rat intestinal epithelial cell cultures with the oxidosqualene cyclase inhibitor, 3 beta-[2-(diethylamino)-ethoxy]androst-5-en-17-one (U18666A), resulted in an accumulation of squalene 2,3:22,23-dioxide (SDO). When U18666A was withdrawn and the cells were treated with the sterol 14 alpha-demethylase inhibitor, ketoconazole, SDO was metabolized to a product identified as 24(S),25-epoxylanosterol. To test the biological effects and cellular metabolism of this compound, we prepared 24(RS),25-epoxylanosterol by chemical synthesis. The epimeric mixture of 24,25-epoxylanosterols could be resolved by high performance liquid chromatography on a wide-pore, non-endcapped, reverse phase column. Both epimers were effective suppressors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity of IEC-6 cells. The suppressive action of the natural epimer, 24(S),25-epoxylanosterol, but not that of 24(R),25-epoxylanosterol could be completely prevented by ketoconazole. IEC-6 cells could efficiently metabolize biosynthetic 24(S),25-epoxy[ 3 H]anosterol mainly to the known reductase-suppressor 24(S),25-epoxycholesterol. This metabolism was substantially reduced by ketoconazole. These data support the conclusion that 24(S),25-epoxylanosterol per se is not a suppressor of HMG-CoA reductase activity but is a precursor to a regulatory oxysterol(s). It has recently been reported that 25-hydroxycholesterol can occur naturally in cultured cells in amounts sufficient to effect regulation of HMG-CoA reductase. In order to investigate the biological effects of possible precursors of 25-hydroxycholesterol, we chemically synthesized 25-hydroxylanosterol and 25-hydroxylanostene-3-one. Both oxylanosterol derivatives suppressed cellular sterol synthesis at the level of HMG-CoA reductase. (Abstract Truncated)

  20. Legal Instruments of Regulation of Development of Banking Activity in Ukraine

    Directory of Open Access Journals (Sweden)

    Senyshch Pavlo M.

    2014-03-01

    Full Text Available The article considers main approaches to identification of essence of legal instruments of regulation of development of the banking activity, identifies the mechanism of legal regulation of the banking activity and its elements and justifies the system and form of legal regulation of the banking activity in Ukraine. It describes subjects of legal regulation of the banking activity at the international level, which are the Basel Committee on Banking Supervision, European Central Bank, IMF, International Financial Reporting Standards Foundation and others. The article considers specific features of the regulatory requirements of Basel II and Basel III and specific features of their introduction into the banking activity. It describes anti-cyclic measures offered by the Basel Committee, which should facilitate formation of such conditions, under which the banking sector could have a lower level of leverage and stability with respect to influence of system risks. Significant attention is paid to international instruments of regulation of the banking activity, which include the following legal acts: Uniform Rules for Collections, Uniform Customs and Practice for Documentary Credits, and Unified Rules for Loan Guarantees. The article shows that the share of subordinate legal acts is significant in the Ukrainian system of banking regulatory and legal acts since the state cannot operatively react to the changing processes in banking at the legislative level and, that is why, basic provisions on carrying out banking activity should be fixed in law.

  1. Active Inference, homeostatic regulation and adaptive behavioural control.

    Science.gov (United States)

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-11-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Elevated atmospheric CO2 increases microbial growth rates and enzymes activity in soil

    Science.gov (United States)

    Blagodatskaya, Evgenia; Blagodatsky, Sergey; Dorodnikov, Maxim; Kuzyakov, Yakov

    2010-05-01

    Increasing the belowground translocation of assimilated carbon by plants grown under elevated CO2 can cause a shift in the structure and activity of the microbial community responsible for the turnover of organic matter in soil. We investigated the long-term effect of elevated CO2 in the atmosphere on microbial biomass and specific growth rates in root-free and rhizosphere soil. The experiments were conducted under two free air carbon dioxide enrichment (FACE) systems: in Hohenheim and Braunschweig, as well as in the intensively managed forest mesocosm of the Biosphere 2 Laboratory (B2L) in Oracle, AZ. Specific microbial growth rates (μ) were determined using the substrate-induced respiration response after glucose and/or yeast extract addition to the soil. We evaluated the effect of elevated CO2 on b-glucosidase, chitinase, phosphatase, and sulfatase to estimate the potential enzyme activity after soil amendment with glucose and nutrients. For B2L and both FACE systems, up to 58% higher μ were observed under elevated vs. ambient CO2, depending on site, plant species and N fertilization. The μ-values increased linearly with atmospheric CO2 concentration at all three sites. The effect of elevated CO2 on rhizosphere microorganisms was plant dependent and increased for: Brassica napus=Triticum aestivumyeast extract then for those growing on glucose, i.e. the effect of elevated CO2 was smoothed on rich vs. simple substrate. So, the r/K strategies ratio can be better revealed by studying growth on simple (glucose) than on rich substrate mixtures (yeast extract). After adding glucose, enzyme activities under elevated CO2 were 1.2-1.9-fold higher than under ambient CO2. This indicates the increased activity of microorganisms, which leads to accelerated C turnover in soil under elevated CO2. Our results clearly showed that the functional characteristics of the soil microbial community (i.e. specific growth rates and enzymes activity) rather than total microbial biomass

  3. Synaptic activity regulates AMPA receptor trafficking through different recycling pathways

    Science.gov (United States)

    Zheng, Ning; Jeyifous, Okunola; Munro, Charlotte; Montgomery, Johanna M; Green, William N

    2015-01-01

    Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites. DOI: http://dx.doi.org/10.7554/eLife.06878.001 PMID:25970033

  4. Active Learning and Self-Regulation Enhance Student Teachers' Professional Competences

    Science.gov (United States)

    Virtanen, Päivi; Niemi, Hannele M.; Nevgi, Anne

    2017-01-01

    The study identifies the relationships between active learning, student teachers' self-regulated learning and professional competences. Further, the aim is to investigate how active learning promotes professional competences of student teachers with different self-regulation profiles. Responses from 422 student teachers to an electronic survey…

  5. Study on CO{sub 2} absorption enhancement by adding active carbon particles into MEA solution

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Juan; Sun, Rui; Ma, Lian; Sun, Shaozeng [Harbin Institute of Technology, Harbin (China). School of Energy Science and Engineering

    2013-07-01

    The chemical absorption of CO{sub 2} is generally recognized as the most efficient post-combustion technology of CO{sub 2} separation at present. A study on CO{sub 2} absorption enhancement by adding small particles of active carbon into MEA solution is investigated within a self-designed glass stirring tank. Experiments of different particle loadings and different particle sizes have been conducted. When active carbon particle concentration is fewer, compared to the absorption rate of CO{sub 2} gas absorbed by MEA aqueous solution, the role of active carbon adsorption CO{sub 2} gas is negligible. The enhancement efficiency of CO{sub 2} absorption could be improved by 10% to the upmost in this liquid-particle system.

  6. Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.

    Science.gov (United States)

    Fan, Rongrong; Toubal, Amine; Goñi, Saioa; Drareni, Karima; Huang, Zhiqiang; Alzaid, Fawaz; Ballaire, Raphaelle; Ancel, Patricia; Liang, Ning; Damdimopoulos, Anastasios; Hainault, Isabelle; Soprani, Antoine; Aron-Wisnewsky, Judith; Foufelle, Fabienne; Lawrence, Toby; Gautier, Jean-Francois; Venteclef, Nicolas; Treuter, Eckardt

    2016-07-01

    Humans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet-induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor-dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D.

  7. Co-crystallization: An approach to improve the performance characteristics of active pharmaceutical ingredients

    OpenAIRE

    Jignasa Ketan Savjani

    2015-01-01

    Co-crystal chemistry has recently attracted supramolecular scientists. Co-crystals are comprising of hydrogen boding assembly between different molecules. Many issues related to performance characteristics of an active pharmaceutical ingredient (API) can be resolved using co-crystallization approach. Proper understanding of crystal structure of an API is required for successful formation of co-crystals with the selected co-former. This review article focus on explanation about co-crystals, in...

  8. Co-operative approaches to regulation

    National Research Council Canada - National Science Library

    Huigen, Hans; Organisation for Economic Co-operation and Development

    1997-01-01

    The case studies in this occasional paper are about ways in which governments and businesses are seeking to address economic and social problems by using new forms of co-operation that are different...

  9. Erythroid Kruppel-like factor (EKLF) is recruited to the γ-globin gene promoter as a co-activator and is required for γ-globin gene induction by short-chain fatty acid derivatives

    Science.gov (United States)

    Perrine, Susan P.; Mankidy, Rishikesh; Boosalis, Michael S.; Bieker, James J.; Faller, Douglas V.

    2011-01-01

    Objectives The erythroid Kruppel-like factor (EKLF) is an essential transcription factor for β-type globin gene switching, and specifically activates transcription of the adult β-globin gene promoter. We sought to determine if EKLF is also required for activation of the γ-globin gene by short-chain fatty acid (SCFA) derivatives, which are now entering clinical trials. Methods The functional and physical interaction of EKLF and co-regulatory molecules with the endogenous human globin gene promoters was studied in primary human erythroid progenitors and cell lines, using chromatin immunoprecipitation (ChIP) assays and genetic manipulation of the levels of EKLF and co-regulators. Results and conclusions Knockdown of EKLF prevents SCFA-induced expression of the γ-globin promoter in a stably expressed μLCRβprRlucAγprFluc cassette, and prevents induction of the endogenous γ-globin gene in primary human erythroid progenitors. EKLF is actively recruited to endogenous γ-globin gene promoters after exposure of primary human erythroid progenitors, and murine hematopoietic cell lines, to SCFA derivatives. The core ATPase BRG1 subunit of the human SWI/WNF complex, a ubiquitous multimeric complex that regulates gene expression by remodeling nucleosomal structure, is also required for γ-globin gene induction by SCFA derivatives. BRG1 is actively recruited to the endogenous γ-globin promoter of primary human erythroid progenitors by exposure to SCFA derivatives, and this recruitment is dependent upon the presence of EKLF. These findings demonstrate that EKLF, and the co-activator BRG1, previously demonstrated to be required for definitive or adult erythropoietic patterns of globin gene expression, are co-opted by SCFA derivatives to activate the fetal globin genes. PMID:19220418

  10. Co-ordinate regulation of the cystic fibrosis and multidrug resistance genes in cystic fibrosis knockout mice.

    Science.gov (United States)

    Trezise, A E; Ratcliff, R; Hawkins, T E; Evans, M J; Freeman, T C; Romano, P R; Higgins, C F; Colledge, W H

    1997-04-01

    The cystic fibrosis (Cftr and multidrug resistance (Mdr1) genes encode structurally similar proteins which are members of the ABC transporter superfamily. These genes exhibit complementary patterns of expression in vivo, suggesting that the regulation of their expression may be co-ordinated. We have tested this hypothesis in vivo by examining Cftr and Mdr1 expression in cystic fibrosis knockout transgenic mice (Cftr(tm1CAM)). Cftr mRNA expression in Cftr(tm1CAM)/Cftr(tm1CAM) mice was 4-fold reduced in the intestine, as compared with littermate wild-type mice. All other Cftr(tm1CAM)/Cftr(tm1CAM) mouse tissues examined showed similar reductions in Cftr expression. In contrast, we observed a 4-fold increase in Mdr1 mRNA expression in the intestines of neonatal and 3- to 4-week-old Cftr(tm1CAM)/Cftr(tm1CAM) mice, as compared with age-matched +/+ mice, and an intermediate level of Mdr1 mRNA in heterozygous Cftr(tm1CAM) mice. In 10-week-old, Cftr(tm1CAM)/Cftr(tm1CAM) mice and in contrast to the younger mice, Mdr1 mRNA expression was reduced, by 3-fold. The expression of two control genes, Pgk-1 and Mdr2, was similar in all genotypes, suggesting that the changes in Mdr1 mRNA levels observed in the Cftr(tm1CAM)/Cftr(tm1CAM) mice are specific to the loss of Cftr expression and/or function. These data provide further evidence supporting the hypothesis that the regulation Cftr and Mdr1 expression is co-ordinated in vivo, and that this co-ordinate regulation is influenced by temporal factors.

  11. Preparation and Characterization of K2CO3-Activated Kraft Lignin Carbon

    Directory of Open Access Journals (Sweden)

    Xian-fa Li

    2016-01-01

    Full Text Available A series of activated carbons (ACs were prepared by K2CO3 activation from kraft lignin (KL that was recovered from papermaking black liquor. The effects of process parameters such as the activation temperature (AT, activated period, K2CO3 to KL mass ratio, and N2 flow rate on the characteristics of the final product were determined. The ACs were characterized using nitrogen adsorption, morphology, and fractal dimension analyses. The results showed that the AT was the main factor influencing the yield, surface area, and pore structure. The yield of ACs obviously decreased from 50.6% to 20.5% with increasing AT from 600 °C to 1000 °C, and decreased with increasing K2CO3/KL mass ratio. Activation time and N2 flow rate had slight effect on the yield of ACs. The surface area and total pore volume increased as the AT rose to 900 °C and then decreased with further increases in temperature. The maximum surface area and total pore volume were 1816.3 m2/g and 1.26 cm3/g, respectively, at a K2CO3 to KL mass ratio of 3:1, AT of 900 °C, activation time of 2 h, and N2 flow rate of 70 cm3/min. The pore structure of the ACs could be tailored by controlling the AT. As the AT was increased from 700 to 1000 °C, the mesoporosity increased from 11.6% to 95.9%. SEM images indicated that the morphology of ACs was modified by the AT. The K2CO3 was partially recycled.

  12. Commission for Energy regulation (CRE) - Activity report June 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  13. Commission for Energy regulation (CRE) - Activity report June 2007

    International Nuclear Information System (INIS)

    2007-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets, Natural gas

  14. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    International Nuclear Information System (INIS)

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. [ 3 H]PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 μM. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRPγS and GDPβS, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA)

  15. Development of a cost-effective CO2 adsorbent from petroleum coke via KOH activation

    Science.gov (United States)

    Jang, Eunji; Choi, Seung Wan; Hong, Seok-Min; Shin, Sangcheol; Lee, Ki Bong

    2018-01-01

    The capture of CO2 via adsorption is considered an effective technology for decreasing global warming issues; hence, adsorbents for CO2 capture have been actively developed. Taking into account cost-effectiveness and environmental concerns, the development of CO2 adsorbents from waste materials is attracting considerable attention. In this study, petroleum coke (PC), which is the carbon residue remaining after heavy oil upgrading, was used to produce high-value-added porous carbon for CO2 capture. Porous carbon materials were prepared by KOH activation using different weight ratios of KOH/PC (1:1, 2:1, 3:1, and 4:1) and activation temperatures (600, 700, and 800 °C). The specific surface area and total pore volume of resulting porous carbon materials increased with KOH amount, reaching up to 2433 m2/g and 1.11 cm3/g, respectively. The sample prepared under moderate conditions with a KOH/PC weight ratio of 2:1 and activation temperature of 700 °C exhibited the highest CO2 adsorption uptake of 3.68 mmol/g at 25 °C and 1 bar. Interestingly, CO2 adsorption uptake was linearly correlated with the volume of micropores less than 0.8 nm, indicating that narrow micropore volume is crucial for CO2 adsorption. The prepared porous carbon materials also exhibited good selectivity for CO2 over N2, rapid adsorption, facile regeneration, and stable adsorption-desorption cyclic performance, demonstrating potential as a candidate for CO2 capture.

  16. Food safety regulatory systems in Europe and China:A study of how co-regulation can improve regulatory effectiveness

    Institute of Scientific and Technical Information of China (English)

    Kevin Chen; WANG Xin-xin; SONG Hai-ying

    2015-01-01

    Food safety has received a great deal of attention in both developed and developing countries in recent years. In China, the numerous food scandals and scares that have struck over the past decade have spurred signiifcant food safety regulatory reform, which has been increasingly oriented towards the public-private partnership model adopted by the Europe Union’s (EU) food safety regulatory system. This paper analyzes the development of both the EU’s and China’s food safety regu-latory systems, identiifes the current chalenges for China and additionaly considers the role of public-private partnership. The success of co-regulation in the food regulatory system would bring signiifcant beneifts and opportunities for China. Finaly, this paper recommends additional measures like training and grants to improve the private’s sector effectiveness in co-regulating China’s food safety issues.

  17. Lipopolysaccharide derived from the rumen down-regulates stearoyl-CoA desaturase 1 expression and alters fatty acid composition in the liver of dairy cows fed a high-concentrate diet.

    Science.gov (United States)

    Xu, Tianle; Tao, Hui; Chang, Guangjun; Zhang, Kai; Xu, Lei; Shen, Xiangzhen

    2015-03-07

    Dairy cows are often fed a high-concentrate diet to meet lactating demands, yet long-term concentrate feeding induces subacute ruminal acidosis (SARA) and leads to a decrease in milk fat. Stearoyl-CoA desaturase1 (SCD1) participates in fatty acid biosynthesis in the liver of lactating ruminants. Here, we conducted this study to investigate the impact of lipopolysaccharide derived from the rumen on SCD1 expression and on fatty acid composition in the liver of dairy cows fed a high-concentrate diet. Eight multiparous mid-lactating Holstein cows (455 ± 28 kg) were randomly assigned into two groups in the experiment and were fed a low-concentrate diet (LC) or high-concentrate diet (HC) for 18 weeks. The results showed that the total volatile fatty acids and lactic acid accumulated in the rumen, leading to a decreased rumen pH and elevated lipopolysaccharides (LPSs) in the HC group. The long chain fatty acid profile in the rumen and hepatic vein was remarkably altered in the animals fed the HC diet. The triglyceride (TG), non-esterified fatty acid (NEFA) and total cholesterol (TCH) content in the plasma was significantly decreased, whereas plasma glucose and insulin levels were increased. The expression of SCD1 in the liver was significantly down-regulated in the HC group. In regards to transcriptional regulators, the expression of sterol regulatory element binding transcription factors (SREBF1c, SREBF2) and SREBP cleavage activating protein (SCAP) was down-regulated, while peroxisome proliferator-activated receptor α (PPARα) was up-regulated. These data indicate that lipopolysaccharide derived from the rumen down-regulates stearoyl-CoA desaturase 1 expression and alters fatty acid composition in the liver of dairy cows fed a high-concentrate diet.

  18. Physical Activity, Self-Regulation, and Early Academic Achievement in Preschool Children

    Science.gov (United States)

    Becker, Derek R.; McClelland, Megan M.; Loprinzi, Paul; Trost, Stewart G.

    2014-01-01

    Research Findings: The present study investigated whether active play during recess was associated with self-regulation and academic achievement in a prekindergarten sample. A total of 51 children in classes containing approximately half Head Start children were assessed on self-regulation, active play, and early academic achievement. Path…

  19. Effect of food deprivation and hormones of glucose homeostasis on the acetyl CoA carboxylase activity in mouse brain: a potential role of acc in the regulation of energy balance

    Directory of Open Access Journals (Sweden)

    Mukherjee Amrita

    2006-02-01

    Full Text Available Abstract We studied the regulation of brain acetyl CoA carboxylase (ACC activity during food deprivation and under the influence of hormones of glucose homeostasis: glucagon and insulin. Mice were deprived of food and water for time periods of 1, 3, 6, 9, 12 and 24 hours and were then allowed to re-feed for 5, 30 and 60 minutes. Mice that were deprived for up to 6 h, and then re-fed for 60 min, consumed the same amount of food compared to the ad libitum (control animals. However, after 9 h of deprivation, mice consumed only 50% of food present even after 1 h of re-feeding, compared to the controls. The ACC activity was measured in the whole mouse brain of controls and after 1, 3, 6, 9, 12, and 24 h of food deprivation. Brain extracts assayed from control mice expressed an ACC activity of 0.988 ± 0.158 fmol/min/mg tissue without citrate and 0.941 ± 0.175 fmol/min/mg tissue with citrate. After 1 h of food deprivation, the total ACC activity without citrate decreased to 0.575 ± 0.087 fmol/min/mg and in the presence of citrate, 0.703 ± 0.036 fmol/min/mg activity was measured. The citrate-dependent ACC activity decreased over time, with only 0.478 ± 0.117 fmol/min/mg of activity remaining after 24 h. Intraperitoneal (i.p. injections of insulin, glucagon and phosphate buffered saline (PBS were performed and whole brain ACC activity measured. After hormone administration, there were no significant differences in ACC activity in the presence of citrate. However, in the absence of citrate, there was a significant 20% decrease in ACC activity with glucagon (1.36 ± 0.09 fmol/min/mg and a 33% increase with insulin (2.49 ± 0.11 fmol/min/mg injections compared to PBS controls (1.67 ± 0.08 fmol/min/mg. Neuropeptide Y (NPY levels of corresponding brain extracts were measured by ELISA (OD using anti-NPY antibody and showed an 18% decrease upon insulin injection (0.093 ± 0.019 and a 50% increase upon glucagon injection (0.226 ± 0.084 as compared to

  20. Regulation of AMP-activated protein kinase by natural and synthetic activators

    Directory of Open Access Journals (Sweden)

    David Grahame Hardie

    2016-01-01

    Full Text Available The AMP-activated protein kinase (AMPK is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.

  1. High efficiency of CO2-activated graphite felt as electrode for vanadium redox flow battery application

    Science.gov (United States)

    Chang, Yu-Chung; Chen, Jian-Yu; Kabtamu, Daniel Manaye; Lin, Guan-Yi; Hsu, Ning-Yih; Chou, Yi-Sin; Wei, Hwa-Jou; Wang, Chen-Hao

    2017-10-01

    A simple method for preparing CO2-activated graphite felt as an electrode in a vanadium redox flow battery (VRFB) was employed by the direct treatment in a CO2 atmosphere at a high temperature for a short period. The CO2-activated graphite felt demonstrates excellent electrochemical activity and reversibility. The VRFB using the CO2-activated graphite felts in the electrodes has coulombic, voltage, and energy efficiencies of 94.52%, 88.97%, and 84.15%, respectively, which is much higher than VRFBs using the electrodes of untreated graphite felt and N2-activated graphite felt. The efficiency enhancement was attributed to the higher number of oxygen-containing functional groups on the graphite felt that are formed during the CO2-activation, leading to improving the electrochemical behaviour of the resultant VRFB.

  2. Graphene quantum dots /LaCoO{sub 3}/attapulgite heterojunction photocatalysts with improved photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Wei; Li, Xiazhang [Changzhou University, Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou (China); Chinese Academy of Science, R and D Center of Xuyi Attapulgite Applied Technology, Xuyi (China)

    2017-04-15

    A new nanocomposite of graphene quantum dots/LaCoO{sub 3}/attapulgite (GQDs/LaCoO{sub 3}/ATP) was prepared by a facile impregnation method and was applied to degradation of the organic pollutants as photocatalyst under visible light irradiation. Multiple techniques were used to characterize the structures, morphologies and photocatalytic activities of samples. The photocatalytic activity of the GQDs/LaCoO{sub 3}/ATP nanocomposites was effectively evaluated using Methylene blue (MB), antibiotic agent chlortetracycline (CHL) and tetracycline hydrochloride (TC). The as-synthesized GQDs/LaCoO{sub 3}/ATP nanocomposites exhibited higher photocatalytic activities than LaCoO{sub 3}/ATP, which showed a broad spectrum of photocatalytic degradation activity. The results of ESR and free radicals trapping experiments indicated that {sup circle} OH and h {sup +} were the main species for the photocatalytic degradation. GQDs played a significant role in the photocatalytic activity improvement of LaCoO{sub 3}/ATP, increasing the visible light absorption, slowing the recombination and improving the charge transfer. (orig.)

  3. Enhancing the smoothness of joint motion induced by functional electrical stimulation using co-activation strategies

    Directory of Open Access Journals (Sweden)

    Ruppel Mirjana

    2017-09-01

    Full Text Available The motor precision of today’s neuroprosthetic devices that use artificial generation of limb motion using Functional Electrical Stimulation (FES is generally low. We investigate the adoption of natural co-activation strategies as present in antagonistic muscle pairs aiming to improve motor precision produced by FES. In a test in which artificial knee-joint movements were generated, we could improve the smoothness of FES-induced motion by 513% when applying co-activation during the phases in which torque production is switched between muscles – compared to no co-activation. We further demonstrated how the co-activation level influences the joint stiffness in a pendulum test.

  4. Targeting Dysregulated Epigenetic Enzymes for Prostate Cancer Treatment

    Science.gov (United States)

    2016-10-01

    results from 3 putative mechanisms, mutations in the androgen receptor, mutation in the DNA damage repair pathway and DNA damage associated secretory...PCAF (human), piccolo NuA4 ( yeast ), and SIRT2 (human) were overexpressed in BL21(DE3), and purified on a Ni-charged HiTrap HP affinity column (GE... mutations have been recognized (37), and activity may also be altered through other posttranslational mechanisms (38). Follow-up experiments strongly

  5. The effects of reduced CO{sub 2} emissions on employment; Sysselsettingsvirkninger av redusert CO{sub 2}-utslipp

    Energy Technology Data Exchange (ETDEWEB)

    Mathiesen, L

    1995-06-01

    This report discusses how reducing the CO{sub 2} emission might affect employment, adaptation and job mobility between trades. It confirms and expands the results of many previous studies. The socio-economic costs involved in regulation of greenhouse gas emissions appear to be low and perhaps negative, and very unevenly distributed on the sectors which must be regulated if the emission goals are to be achieved. The author`s analyses show that in addition to affecting the transport sectors, regulations have an especially strong impact on trades within the processing industries such as refining of crude oil, production of ferro alloys, fertilizers, cement and primary aluminium. For the Norwegian CO{sub 2} emissions in 2000 not to exceed the 1989 level, the activities within crude oil refining and ferro alloys production must be halved and the activities within the three other industries must go down by 10-15%. This ranking is very stable under changes in common external conditions provided all the sectors face the same tax per unit emitted. The trades most strongly influenced by regulations are mostly found in places with few alternative job possibilities, which results in frictional unemployment. Some of the unemployed may get lost forever so that the unemployment becomes permanent. However, less than 1% of the total manpower of Norway work in the five sectors and so the loss of work places will be 0.2%, or 4000. 35 refs., 9 figs., 6 tabs.

  6. Gasification under CO2–Steam Mixture: Kinetic Model Study Based on Shared Active Sites

    Directory of Open Access Journals (Sweden)

    Xia Liu

    2017-11-01

    Full Text Available In this work, char gasification of two coals (i.e., Shenfu bituminous coal and Zunyi anthracite and a petroleum coke under a steam and CO2 mixture (steam/CO2 partial pressures, 0.025–0.075 MPa; total pressures, 0.100 MPa and CO2/steam chemisorption of char samples were conducted in a Thermogravimetric Analyzer (TGA. Two conventional kinetic models exhibited difficulties in exactly fitting the experimental data of char–steam–CO2 gasification. Hence, a modified model based on Langmuir–Hinshelwood model and assuming that char–CO2 and char–steam reactions partially shared active sites was proposed and had indicated high accuracy for estimating the interactions in char–steam–CO2 reaction. Moreover, it was found that two new model parameters (respectively characterized as the amount ratio of shared active sites to total active sites in char–CO2 and char–steam reactions in the modified model hardly varied with gasification conditions, and the results of chemisorption indicate that these two new model parameters mainly depended on the carbon active sites in char samples.

  7. SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

    Science.gov (United States)

    Barker, Thomas H; Baneyx, Gretchen; Cardó-Vila, Marina; Workman, Gail A; Weaver, Matt; Menon, Priya M; Dedhar, Shoukat; Rempel, Sandra A; Arap, Wadih; Pasqualini, Renata; Vogel, Viola; Sage, E Helene

    2005-10-28

    SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

  8. Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane.

    Science.gov (United States)

    De Gois, Stéphanie; Slama, Patrick; Pietrancosta, Nicolas; Erdozain, Amaia M; Louis, Franck; Bouvrais-Veret, Caroline; Daviet, Laurent; Giros, Bruno

    2015-07-17

    Dopamine (DA) is a major regulator of sensorimotor and cognitive functions. The DA transporter (DAT) is the key protein that regulates the spatial and temporal activity of DA release into the synaptic cleft via the rapid reuptake of DA into presynaptic termini. Several lines of evidence have suggested that transporter-interacting proteins may play a role in DAT function and regulation. Here, we identified the tetratricopeptide repeat domain-containing protein Ctr9 as a novel DAT binding partner using a yeast two-hybrid system. We showed that Ctr9 is expressed in dopaminergic neurons and forms a stable complex with DAT in vivo via GST pulldown and co-immunoprecipitation assays. In mammalian cells co-expressing both proteins, Ctr9 partially colocalizes with DAT at the plasma membrane. This interaction between DAT and Ctr9 results in a dramatic enhancement of DAT-mediated DA uptake due to an increased number of DAT transporters at the plasma membrane. We determined that the binding of Ctr9 to DAT requires residues YKF in the first half of the DAT C terminus. In addition, we characterized Ctr9, providing new insight into this protein. Using three-dimensional modeling, we identified three novel tetratricopeptide repeat domains in the Ctr9 sequence, and based on deletion mutation experiments, we demonstrated the role of the SH2 domain of Ctr9 in nuclear localization. Our results demonstrate that Ctr9 localization is not restricted to the nucleus, as previously described for the transcription complex Paf1. Taken together, our data provide evidence that Ctr9 modulates DAT function by regulating its trafficking. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Catalytic performance of activated carbon supported cobalt catalyst for CO2 reforming of CH4.

    Science.gov (United States)

    Zhang, Guojie; Su, Aiting; Du, Yannian; Qu, Jiangwen; Xu, Ying

    2014-11-01

    Syngas production by CO2 reforming of CH4 in a fixed bed reactor was investigated over a series of activated carbon (AC) supported Co catalysts as a function of Co loading (between 15 and 30wt.%) and calcination temperature (Tc=300, 400 or 500°C). The catalytic performance was assessed through CH4 and CO2 conversions and long-term stability. XRD and SEM were used to characterize the catalysts. It was found that the stability of Co/AC catalysts was strongly dependent on the Co loading and calcination temperature. For the loadings (25wt.% for Tc=300°C), stable activities have been achieved. The loading of excess Co (>wt.% 25) causes negative effects not only on the performance of the catalysts but also on the support surface properties. In addition, the experiment showed that ultrasound can enhance and promote dispersion of the active metal on the carrier, thus improving the catalytic performance of the catalyst. The catalyst activity can be long-term stably maintained, and no obvious deactivation has been observed in the first 2700min. After analyzing the characteristics, a reaction mechanism for CO2 reforming of CH4 over Co/AC catalyst was proposed. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Co-assembly of viral envelope glycoproteins regulates their polarized sorting in neurons.

    Directory of Open Access Journals (Sweden)

    Rafael Mattera

    2014-05-01

    Full Text Available Newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. Although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. We studied the polarized sorting of the attachment (NiV-G and fusion (NiV-F glycoproteins of Nipah virus (NiV, a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. When expressed individually, NiV-G exhibited a non-polarized distribution, whereas NiV-F was specifically sorted to the somatodendritic domain. Polarized sorting of NiV-F was dependent on interaction of tyrosine-based signals in its cytosolic tail with the clathrin adaptor complex AP-1. Co-expression of NiV-G with NiV-F abolished somatodendritic sorting of NiV-F due to incorporation of NiV-G•NiV-F complexes into axonal transport carriers. We propose that faster biosynthetic transport of unassembled NiV-F allows for its proteolytic activation in the somatodendritic domain prior to association with NiV-G and axonal delivery of NiV-G•NiV-F complexes. Our study reveals how interactions of viral glycoproteins with the host's transport machinery and between themselves regulate their polarized sorting in neurons.

  11. Applying Web-Based Co-Regulated Learning to Develop Students' Learning and Involvement in a Blended Computing Course

    Science.gov (United States)

    Tsai, Chia-Wen

    2015-01-01

    This research investigated, via quasi-experiments, the effects of web-based co-regulated learning (CRL) on developing students' computing skills. Two classes of 68 undergraduates in a one-semester course titled "Applied Information Technology: Data Processing" were chosen for this research. The first class (CRL group, n = 38) received…

  12. Activating Transcription Factor 3 regulates in part the enhanced tumour cell cytotoxicity of the histone deacetylase inhibitor M344 and cisplatin in combination

    Directory of Open Access Journals (Sweden)

    St Germain Carly

    2010-09-01

    Full Text Available Abstract Background Activating Transcription Factor (ATF 3 is a key regulator of the cellular integrated stress response whose expression has also been correlated with pro-apoptotic activities in tumour cell models. Combination treatments with chemotherapeutic drugs, such as cisplatin, and histone deacetylase (HDAC inhibitors have been demonstrated to enhance tumour cell cytotoxicity. We recently demonstrated a role for ATF3 in regulating cisplatin-induced apoptosis and others have shown that HDAC inhibition can also induce cellular stress. In this study, we evaluated the role of ATF3 in regulating the co-operative cytotoxicity of cisplatin in combination with an HDAC inhibitor. Results The HDAC inhibitor M344 induced ATF3 expression at the protein and mRNA level in a panel of human derived cancer cell lines as determined by Western blot and quantitative RT-PCR analyses. Combination treatment with M344 and cisplatin lead to increased induction of ATF3 compared with cisplatin alone. Utilizing the MTT cell viability assay, M344 treatments also enhanced the cytotoxic effects of cisplatin in these cancer cell lines. The mechanism of ATF3 induction by M344 was found to be independent of MAPKinase pathways and dependent on ATF4, a known regulator of ATF3 expression. ATF4 heterozygote (+/- and knock out (-/- mouse embryonic fibroblast (MEF as well as chromatin immunoprecipitation (ChIP assays were utilized in determining the mechanistic induction of ATF3 by M344. We also demonstrated that ATF3 regulates the enhanced cytotoxicity of M344 in combination with cisplatin as evidenced by attenuation of cytotoxicity in shRNAs targeting ATF3 expressing cells. Conclusion This study identifies the pro-apoptotic factor, ATF3 as a novel target of M344, as well as a mediator of the co-operative effects of cisplatin and M344 induced tumour cell cytotoxicity.

  13. Synthesis of Co/N-HNTs composites and investigation on its catalytic activity for H2 generation

    International Nuclear Information System (INIS)

    Zhao, Dongcui; Cheng, Zhilin; Nan, Zhaodong

    2016-01-01

    Co/N-HNTs composites were synthesized via a one-pot solvothermal method, where amine functional halloysite nanotubes (N-HNTs) were used as support materials. Effects of sulfosuccinate sodium salt (AOT), an anionic surfactant, on morphology and dispersibility of Co particles anchored at the N-HNTs were studied. The dispersibility of the Co particles was promoted with the increase of the AOT concentration. The as-obtained composite was used as a catalyst to generate H 2 gas by hydrolysis of NaBH 4 solution. The catalytic activity of the composite was significantly enhanced than the pure Co and Co/graphene composite at the same experimental conditions reported by our laboratory, and the catalyst was conveniently separated from the solution by a magnet. The catalytic activity was enhanced when the dispersibility of the Co particles was improved at the surface of the N-HNTs and the Co content contained in the composite was lowed. At the same time, the Co particles anchored at the inner surface of the N-HNTs resulted in higher catalytic activity, where the Co particles may bond with nitrogen atoms. The activation energy for the hydrolysis of NaBH 4 was calculated to be about 15.42 kJ mol −1 . The catalyst can be continuously used for four times with about the same catalytic activity. - Highlights: • Co/N-HNTs composites are synthesized. • The dispersibility and morphology of the Co particles anchored at the N-HNTs are modified by AOT. • The composite shows higher catalytic activity for production H 2 gas.

  14. Experience with the 1985 UK ionizing radiation regulations: the regulators' viewpoint

    International Nuclear Information System (INIS)

    Bines, W.P.; Beaver, P.F.

    1991-01-01

    The Ionising Radiations Regulations 1985 achieved UK implementation of the Euratom Basic Safety Standards Directive; interim action has taken account of recent revisions of risk estimates and the regulations will not be revised in advance of renegotiation of the Euratom Directive. Wide ranging consultation, central to the development of health and safety legislation in the UK, leads to greater co-operation between regulators and regulated and more acceptable legislation. Examples of co-operation, also of methods of enforcement and the use made of them, are given. The authors conclude that the regulations have stood the test of experience well. (Author)

  15. Porous carbon from local coconut shell char by CO2 and H2O activation in the presence of K2CO3

    Science.gov (United States)

    Vi, Nguyen Ngoc Thuy; Truyen, Dang Hai; Trung, Bien Cong; An, Ngo Thanh; Van Dung, Nguyen; Long, Nguyen Quang

    2017-09-01

    Vietnamese coconut shell char was activated by steam and carbon dioxide at low temperatures with the presence of K2CO3 as a catalyst. The effects of process parameters on adsorption capability of the product including different ratio of impregnation of activation agents, activation temperature, activation time were investigated in this study. Iodine number, methylene blue adsorption capacity, specific surface area and pore size distribution were measured to assess the properties of the activated carbon. Accordingly, the porous carbon was applied for toluene removal by adsorption technology. Significant increases in specific surface area and the toluene adsorption capacity were observed when the coconut shell char was activated in CO2 flow at 720 °C for 150 minutes and the K2CO3/char weight ratio of 0.5.

  16. The preparation and measurement of activity for 57Co standard solution

    International Nuclear Information System (INIS)

    Yang Jingxia; Yu Yiguang; Du Hongshan; Chen Xilin

    1994-12-01

    In the preparation of 57 Co, the reactions of 56 Fe (d, n) 57 Co and 56 Fe(d,2n) 57 Co were selected by using 8.7 MeV deuteron to radiate natural iron which was electroplated on copper target. The methods of TBP-Benzene extraction and cation exchange were used for separating and purifying 57 Co. The purity of the solution was checked by HPGe γ spectrometer and the total contents of γ impurities were below 0.2%. To prepare the source, silicon gel suspension was electrosprayed on VYNS thin film which was metallized by gold to form a proper source pad. Weighing balance was used to quantitatively prepare the sources. Research on the effects of the working gas pressure and the working voltage on the plateau curve was carried on by the pressurized 4 πβ-γ coincidence equipment. Finally, efficiency extrapolation method was used to accurately measure the specific activity of 57 Co solution by means of changing the discrimination threshold. The total uncertainty is about 1.2%(3σ) . It is shown that the solution is uniform, stable and accuracy with the reliable specific activity through the domestic comparison. (6 figs.; 6 tabs.)

  17. The GABAA Receptor α2 Subunit Activates a Neuronal TLR4 Signal in the Ventral Tegmental Area that Regulates Alcohol and Nicotine Abuse

    Directory of Open Access Journals (Sweden)

    Irina Balan

    2018-04-01

    Full Text Available Alcoholism initiates with episodes of excessive alcohol drinking, known as binge drinking, which is one form of excessive drinking (NIAAA Newsletter, 2004 that is related to impulsivity and anxiety (Ducci et al., 2007; Edenberg et al., 2004 and is also predictive of smoking status. The predisposition of non-alcohol exposed subjects to initiate binge drinking is controlled by neuroimmune signaling that includes an innately activated neuronal Toll-like receptor 4 (TLR4 signal. This signal also regulates cognitive impulsivity, a heritable trait that defines drug abuse initiation. However, the mechanism of signal activation, its function in dopaminergic (TH+ neurons within the reward circuitry implicated in drug-seeking behavior [viz. the ventral tegmental area (VTA], and its contribution to nicotine co-abuse are still poorly understood. We report that the γ-aminobutyric acidA receptor (GABAAR α2 subunit activates the TLR4 signal in neurons, culminating in the activation (phosphorylation/nuclear translocation of cyclic AMP response element binding (CREB but not NF-kB transcription factors and the upregulation of corticotropin-releasing factor (CRF and tyrosine hydroxylase (TH. The signal is activated through α2/TLR4 interaction, as evidenced by co-immunoprecipitation, and it is present in the VTA from drug-untreated alcohol-preferring P rats. VTA infusion of neurotropic herpes simplex virus (HSV vectors for α2 (pHSVsiLA2 or TLR4 (pHSVsiTLR4 but not scrambled (pHSVsiNC siRNA inhibits signal activation and both binge alcohol drinking and nicotine sensitization, suggesting that the α2-activated TLR4 signal contributes to the regulation of both alcohol and nicotine abuse.

  18. PGC-1α functions as a co-suppressor of XBP1s to regulate glucose metabolism

    Directory of Open Access Journals (Sweden)

    Jaemin Lee

    2018-01-01

    Full Text Available Objective: Peroxisome proliferator-activated receptor γ (PPARγ coactivator-1α (PGC-1α promotes hepatic gluconeogenesis by activating HNF4α and FoxO1. PGC-1α expression in the liver is highly elevated in obese and diabetic conditions, leading to increased hepatic glucose production. We previously showed that the spliced form of X-box binding protein 1 (XBP1s suppresses FoxO1 activity and hepatic gluconeogenesis. The shared role of PGC-1α and XBP1s in regulating FoxO1 activity and gluconeogenesis led us to investigate the probable interaction between PGC-1α and XBP1s and its role in glucose metabolism. Methods: We investigated the biochemical interaction between PGC-1α and XBP1s and examined the role of their interaction in glucose homeostasis using animal models. Results: We show that PGC-1α interacts with XBP1s, which plays an anti-gluconeogenic role in the liver by suppressing FoxO1 activity. The physical interaction between PGC-1α and XBP1s leads to suppression of XBP1s activity rather than its activation. Upregulating PGC-1α expression in the liver of lean mice lessens XBP1s protein levels, and reducing PGC-1α levels in obese and diabetic mouse liver restores XBP1s protein induction. Conclusions: Our findings reveal a novel function of PGC-1α as a suppressor of XBP1s function, suggesting that hepatic PGC-1α promotes gluconeogenesis through multiple pathways as a co-activator for HNF4α and FoxO1 and also as a suppressor for anti-gluconeogenic transcription factor XBP1s. Keywords: PGC-1α, XBP1s, Glucose homeostasis, ER stress, UPR, Insulin resistance

  19. Incorporating nitrogen atoms into cobalt nanosheets as a strategy to boost catalytic activity toward CO2 hydrogenation

    Science.gov (United States)

    Wang, Liangbing; Zhang, Wenbo; Zheng, Xusheng; Chen, Yizhen; Wu, Wenlong; Qiu, Jianxiang; Zhao, Xiangchen; Zhao, Xiao; Dai, Yizhou; Zeng, Jie

    2017-11-01

    Hydrogenation of CO2 into fuels and useful chemicals could help to reduce reliance on fossil fuels. Although great progress has been made over the past decades to improve the activity of catalysts for CO2 hydrogenation, more efficient catalysts, especially those based on non-noble metals, are desired. Here we incorporate N atoms into Co nanosheets to boost the catalytic activity toward CO2 hydrogenation. For the hydrogenation of CO2, Co4N nanosheets exhibited a turnover frequency of 25.6 h-1 in a slurry reactor under 32 bar pressure at 150 °C, which was 64 times that of Co nanosheets. The activation energy for Co4N nanosheets was 43.3 kJ mol-1, less than half of that for Co nanosheets. Mechanistic studies revealed that Co4N nanosheets were reconstructed into Co4NHx, wherein the amido-hydrogen atoms directly interacted with the CO2 to form HCOO* intermediates. In addition, the adsorbed H2O* activated amido-hydrogen atoms via the interaction of hydrogen bonds.

  20. 15 CFR 922.72 - Prohibited or otherwise regulated activities-Sanctuary-wide.

    Science.gov (United States)

    2010-01-01

    ... activities-Sanctuary-wide. 922.72 Section 922.72 Commerce and Foreign Trade Regulations Relating to Commerce... OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Channel Islands National Marine Sanctuary § 922.72 Prohibited or otherwise regulated activities—Sanctuary-wide. (a) Except...

  1. Phosphatidic acid regulates signal output by G protein coupled receptors through direct interaction with phospholipase C-beta(1).

    Science.gov (United States)

    Litosch, Irene; Pujari, Rajeshree; Lee, Shawn J

    2009-09-01

    Phosphatidic acid (PA), generated downstream of monomeric Rho GTPases via phospholipase D (PLD) and additionally by diacylglycerol kinases (DGK), both stimulates phospholipase C-beta(1) (PLC-beta(1)) and potentiates stimulation of PLC-beta(1) activity by Galpha(q) in vitro. PA is a potential candidate for integrating signaling by monomeric and heterotrimeric G proteins to regulate signal output by G protein coupled receptors (GPCR), and we have sought to understand the mechanisms involved. We previously identified the region spanning residues 944-957, lying within the PLC-beta(1) C-terminus alphaA helix and flexible loop of the Galpha(q) binding domain, as required for stimulation of lipase activity by PA in vitro. Regulation by PA does not require residues essential for stimulation by Galpha(q) or GTPase activating activity. The present studies evaluated shorter alanine/glycine replacement mutants and finally point mutations to identify Tyr(952) and Ile(955) as key determinants for regulation by PA, assessed by both in vitro enzymatic and cell-based co-transfection assays. Replacement of Tyr(952) and Ile(955), PLC-beta(1) (Y952G/I955G), results in an 85% loss in stimulation by PA relative to WT-PLC-beta(1) in vitro. COS 7 cells co-transfected with PLC-beta(1) (Y952G/I955G) demonstrate a 10-fold increase in the EC(50) for stimulation and a 60% decrease in maximum stimulation by carbachol via Galpha(q) linked m1 muscarinic receptors, relative to cells co-transfected with WT-PLC-beta(1) but otherwise similar conditions. Residues required for regulation by PA are not essential for stimulation by G protein subunits. WT-PLC-beta(1) and PLC-beta(1) (Y952G/I955G) activity is increased comparably by co-transfection with Galpha(q) and neither is markedly affected by co-transfection with Gbeta(1)gamma(2). Inhibiting PLD-generated PA production by 1-butanol has little effect on maximum stimulation, but shifts the EC(50) for agonist stimulation of WT-PLC-beta(1) by 10-fold

  2. PREPARATION, CHARACTERIZATION, ACTIVITY, DEACTIVATION, AND REGENERATION TESTS OF CoO-MoO/ZnO AND CoO-MoO/ZnO-ACTIVATED ZEOLITE CATALYSTS FOR THE HYDROGEN PRODUCTION FROM FUSEL OIL

    Directory of Open Access Journals (Sweden)

    Wega Trisunaryanti

    2010-06-01

    Full Text Available Preparation, characterization, activation, deactivation, and regeneration tests of CoO-MoO/ZnO and CoO-MoO/ZnO-Activated Zeolite (AZ catalysts for the hydrogen production using steam reforming of alcohols in fusel oil have been conducted. Both catalysts were prepared by impregnation of Co and Mo onto ZnO or ZnO-AZ powder then followed by calcination at 400 °C for 5 h under N2 stream. The BET method and pyridine adsorption were used for catalysts characterization. The study of activation, deactivation, and regeneration of catalysts were conducted by using steam reforming method in the semi flow reactor. The reaction condition were: weight ratio of catalysts/feed = 0.1, temperature: 450 °C, duration: 45 min. The gas product was trapped in a 250 mL vacuum pyrex bottle filled with 50 mL of 4 M NaOH solution and analyzed by GC with TCD system to determine H2 existance and HCl titration to determine CO2 produced during the process that was dissolved in NaOH solution. The results showed that CoO-MoO/ZnO-AZ catalyst produced higher gas conversion than CoO-MoO/ZnO catalyst. However, it had short catalyst lifetime due to its high amount of coke deposited during the process. The regeneration test could enhance the catalyst activity. The gas product consisted of H2 (14.70% and CO2 (24.41%.   Keywords: fusel oil, steam reforming, deactivation, regeneration, hydrogen production.

  3. Trainability of muscular activity level during maximal voluntary co-contraction: comparison between bodybuilders and nonathletes.

    Directory of Open Access Journals (Sweden)

    Sumiaki Maeo

    Full Text Available Antagonistic muscle pairs cannot be fully activated simultaneously, even with maximal effort, under conditions of voluntary co-contraction, and their muscular activity levels are always below those during agonist contraction with maximal voluntary effort (MVE. Whether the muscular activity level during the task has trainability remains unclear. The present study examined this issue by comparing the muscular activity level during maximal voluntary co-contraction for highly experienced bodybuilders, who frequently perform voluntary co-contraction in their training programs, with that for untrained individuals (nonathletes. The electromyograms (EMGs of biceps brachii and triceps brachii muscles during maximal voluntary co-contraction of elbow flexors and extensors were recorded in 11 male bodybuilders and 10 nonathletes, and normalized to the values obtained during the MVE of agonist contraction for each of the corresponding muscles (% EMGMVE. The involuntary coactivation level in antagonist muscle during the MVE of agonist contraction was also calculated. In both muscles, % EMGMVE values during the co-contraction task for bodybuilders were significantly higher (P<0.01 than those for nonathletes (biceps brachii: 66±14% in bodybuilders vs. 46±13% in nonathletes, triceps brachii: 74±16% vs. 57±9%. There was a significant positive correlation between a length of bodybuilding experience and muscular activity level during the co-contraction task (r = 0.653, P = 0.03. Involuntary antagonist coactivation level during MVE of agonist contraction was not different between the two groups. The current result indicates that long-term participation in voluntary co-contraction training progressively enhances muscular activity during maximal voluntary co-contraction.

  4. Trainability of Muscular Activity Level during Maximal Voluntary Co-Contraction: Comparison between Bodybuilders and Nonathletes

    Science.gov (United States)

    Maeo, Sumiaki; Takahashi, Takumi; Takai, Yohei; Kanehisa, Hiroaki

    2013-01-01

    Antagonistic muscle pairs cannot be fully activated simultaneously, even with maximal effort, under conditions of voluntary co-contraction, and their muscular activity levels are always below those during agonist contraction with maximal voluntary effort (MVE). Whether the muscular activity level during the task has trainability remains unclear. The present study examined this issue by comparing the muscular activity level during maximal voluntary co-contraction for highly experienced bodybuilders, who frequently perform voluntary co-contraction in their training programs, with that for untrained individuals (nonathletes). The electromyograms (EMGs) of biceps brachii and triceps brachii muscles during maximal voluntary co-contraction of elbow flexors and extensors were recorded in 11 male bodybuilders and 10 nonathletes, and normalized to the values obtained during the MVE of agonist contraction for each of the corresponding muscles (% EMGMVE). The involuntary coactivation level in antagonist muscle during the MVE of agonist contraction was also calculated. In both muscles, % EMGMVE values during the co-contraction task for bodybuilders were significantly higher (Pbodybuilders vs. 46±13% in nonathletes, triceps brachii: 74±16% vs. 57±9%). There was a significant positive correlation between a length of bodybuilding experience and muscular activity level during the co-contraction task (r = 0.653, P = 0.03). Involuntary antagonist coactivation level during MVE of agonist contraction was not different between the two groups. The current result indicates that long-term participation in voluntary co-contraction training progressively enhances muscular activity during maximal voluntary co-contraction. PMID:24260233

  5. Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

    Directory of Open Access Journals (Sweden)

    Nicolas Defarge

    2016-02-01

    Full Text Available Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH, the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations, and not the declared active ingredient glyphosate (G alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

  6. Preparation, Characterization, and Catalytic Activity of MoCo/USY Catalyst on Hydrodeoxygenation Reaction of Anisole

    Science.gov (United States)

    Nugrahaningtyas, K. D.; Suharbiansah, R. S. R.; Rahmawati, F.

    2018-03-01

    This research aims to prepare, characterize, and study the catalytic activity of Molybdenum (Mo) and Cobalt (Co) metal with supporting material Ultra Stable Y-Zeolite (USY), to produce catalysts with activity in hydrotreatment reaction and in order to eliminate impurities compounds that containing unwanted groups heteroatoms. The bimetallic catalysts MoCo/USY were prepared by wet impregnation method with weight variation of Co metal 0%, 2%, 4%, 6%, 8%, and Mo metal 8% (w/w), respectively. Activation method of the catalyst included calcination, oxidation, reduction and the crystallinity was characterized using X-ray diffraction (XRD), the acidity of the catalyst was analyzed using Fourier Transform Infrared Spectroscopy (FT-IR) and gravimetry method, minerals present in the catalyst was analyzed using X-Ray Fluorescence (XRF), and surface of the catalyst was analyzed using Surface Area Analyzer (SAA). Catalytic activity test (benzene yield product) of MoCo/USY on hydrodeoxigenation reaction of anisole aimed to determine the effect of Mo-Co/USY for catalytic activity in the reaction hydrodeoxigenation (HDO) anisole. Based on characterization and test of catalytic activity, it is known that catalytic of MoCo/USY 2% (catalyst B) shows best activities with acidity of 10.209 mmol/g, specific area of catalyst of 426.295 m2/g, pore average of 14.135 Å, total pore volume 0.318 cc/g, and total yield of HDO products 6.06%.

  7. Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity

    Directory of Open Access Journals (Sweden)

    Zhenwei Su

    2017-12-01

    Full Text Available Summary: The brain regulates food intake by processing sensory cues and peripheral physiological signals, but the neural basis of this integration remains unclear. Hypothalamic, agouti-related protein (AgRP-expressing neurons are critical regulators of food intake. AgRP neuron activity is high during hunger and is rapidly reduced by the sight and smell of food. Here, we reveal two distinct components of AgRP neuron activity regulation: a rapid but transient sensory-driven signal and a slower, sustained calorie-dependent signal. We discovered that nutrients are necessary and sufficient for sustained reductions in AgRP neuron activity and that activity reductions are proportional to the calories obtained. This change in activity is recapitulated by exogenous administration of gut-derived satiation signals. Furthermore, we showed that the nutritive value of food trains sensory systems—in a single trial—to drive rapid, anticipatory AgRP neuron activity inhibition. Together, these data demonstrate that nutrients are the primary regulators of AgRP neuron activity. : Su et al. demonstrate that nutrient content in the GI tract is rapidly signaled to hypothalamic neurons activated by hunger. This rapid effect is mediated by three satiation signals that synergistically reduce the activity of AgRP neurons. These findings uncover how hunger circuits in the brain are regulated and raise the possibility that hunger can be pharmacologically controlled. Keywords: calcium imaging, AgRP neurons, calories, satiation signals, sensory regulation, single trial learning, cholecystokinin, CCK, peptide tyrosine tyrosine, PYY, amylin, homeostasis

  8. Resveratrol inhibits Cdk5 activity through regulation of p35 expression

    Directory of Open Access Journals (Sweden)

    Kulkarni Ashok B

    2011-07-01

    Full Text Available Abstract Background We have previously reported that cyclin-dependent kinase 5 (Cdk5 participates in the regulation of nociceptive signaling. Through activation of the ERK1/2 pathway, Tumor Necrosis Factor-α (TNF-α induces expression of Egr-1. This results in the sustained and robust expression of p35, a coactivator of Cdk5, in PC12 cells, thereby increasing Cdk5 kinase activity. The aim of our present study was to test whether resveratrol, a polyphenolic compound with known analgesic activity, can regulate Cdk5/p35 activity. Results Here we used a cell-based assay in which a p35 promoter-luciferase construct was stably transfected in PC12 cells. Our studies demonstrate that resveratrol inhibits p35 promoter activity and also blocks the TNF-α mediated increase in Cdk5 activity in PC12 cells. Resveratrol also inhibits p35 expression and blocks the TNF-α mediated increase in Cdk5 activity in DRG neurons. In the presence of resveratrol, the MEK inhibitor decreased p35 promoter activity, whereas the inhibitors of p38 MAPK, JNK and NF-κB increased p35 promoter activity, indicating that these pathways regulate p35 expression differently. The TNF-α-mediated increase in Egr-1 expression was decreased by resveratrol treatment with a concomitant reduction in p35 expression and protein levels, resulting in reduced Cdk5 kinase activity. Conclusions We demonstrate here that resveratrol regulates p35 promoter activity in PC12 cells and DRG neurons. Most importantly, resveratrol blocks the TNF-α-mediated increase in p35 promoter activity, thereby reducing p35 expression and subsequent Cdk5 kinase activity. This new molecular mechanism adds to the known analgesic effects of resveratrol and confirms the need for identifying new analgesics based on their ability to inhibit Cdk5 activity for effective treatment of pain.

  9. CO{sub 2} injection as pH regulator in refrigeration circuits; Inyeccion de CO{sub 2} como regulador de pH en circuitos de refrigeracion

    Energy Technology Data Exchange (ETDEWEB)

    Belinchon, J.

    2009-07-01

    Water from rivers is not usually suitable for use in cooling circuits of industrial installations, normally because of its high fouling ability. this requires a treatment before use based on the use of fouling inhibitors, biocides and pH regulators. The most commonly used pH regulator is sulfuric acid, a very hazardous chemical product that also generates secondary saline contamination due to the sulfates. Since 2008, Iberdrola Generation, in collaboration with Air Liquid, has been carrying out a pilot project in Cofrentes Nuclear Power Plant focusing on the use of CO{sub 2} as an acidifier of the main condenser cooling system. (Author)

  10. McMYB12 Transcription Factors Co-regulate Proanthocyanidin and Anthocyanin Biosynthesis in Malus Crabapple

    OpenAIRE

    Tian, Ji; Zhang, Jie; Han, Zhen-yun; Song, Ting-ting; Li, Jin-yan; Wang, Ya-ru; Yao, Yun-cong

    2017-01-01

    The flavonoid compounds, proanthocyanidins (PAs), protect plants from biotic stresses, contribute to the taste of many fruits, and are beneficial to human health in the form of dietary antioxidants. In this study, we functionally characterized two Malus crabapple R2R3-MYB transcription factors, McMYB12a and McMYB12b, which co-regulate PAs and anthocyanin biosynthesis. McMYB12a was shown to be mainly responsible for upregulating the expression of anthocyanin biosynthetic genes by binding to th...

  11. Regulation of ABCB1/PGP1-catalysed auxin transport by linker phosphorylation

    DEFF Research Database (Denmark)

    Henrichs, Sina; Wang, Bangjun; Fukao, Yoichiro

    2012-01-01

    Polar transport of the plant hormone auxin is controlled by PIN-and ABCB/PGP-efflux catalysts. PIN polarity is regulated by the AGC protein kinase, PINOID (PID), while ABCB activity was shown to be dependent on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Using co-immunoprecipitation (co-I...

  12. Mast cell activators as novel immune regulators.

    Science.gov (United States)

    Johnson-Weaver, Brandi; Choi, Hae Woong; Abraham, Soman N; Staats, Herman F

    2018-05-26

    Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node composition to regulate the induction of adaptive immune responses. The recognition that mast cells play a beneficial role in host responses to microbial infection and induction of adaptive immunity has provided the rationale to evaluate mast cell activators for use as antimicrobials or vaccine adjuvants. This review summarizes the role of mast cell activators in antimicrobial responses while also discussing the use of different classes of mast cell activators as potent vaccine adjuvants that enhance the induction of protective immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Co-ordinated research activities: Annual report and statistics for 2003

    International Nuclear Information System (INIS)

    2004-07-01

    Article III of the IAEA Statute authorises the Agency to encourage and assist research on, and development and practical application of, atomic energy for peaceful purposes throughout the world and to foster the exchange of scientific and technical information, as well as the exchange of scientists in the field of peaceful uses of atomic energy. The research supported by the Agency is within the framework of the Agency's programmes, sub-programmes and projects that are listed in the approved Programme and Budget of the Agency. These co-ordinated research activities are normally implemented through Co-ordinated Research Projects (CRPs) that bring together research institutes in both developing and developed Member States to collaborate on the research topic of interest. The Agency may also respond to proposals from institutes for participation in the research activities by awarding individual contracts not related to a CRP. A small portion of available funds is used to finance individual projects, which deal with topics covered by the Agency's scientific programme. The Agency also supports several Doctoral CRPs. This new, optional type of CRP has been designed to strengthen promotion of research on nuclear technologies in developing Member States through pair building between agreement holders and contract holders. These CRPs include a PhD training programme at the contract holders' institutions. Three doctoral CRPs are currently being carried out by the Human Health programme. Further information on the Agency's co-ordinated research activities, including current information on CRPs and programme areas supported, information on policies and procedures and the administration of the activities is contained in the Agency's website at http://www-crp.iaea.org. The co-ordinated research activities reported in this document are conducted in support of the following Agency programmes: Nuclear Power; Nuclear Fuel Cycle and Material Technologies; Analysis for Sustainable

  14. Co-ordinated research activities: Annual report and statistics for 2003

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-15

    Article III of the IAEA Statute authorises the Agency to encourage and assist research on, and development and practical application of, atomic energy for peaceful purposes throughout the world and to foster the exchange of scientific and technical information, as well as the exchange of scientists in the field of peaceful uses of atomic energy. The research supported by the Agency is within the framework of the Agency's programmes, sub-programmes and projects that are listed in the approved Programme and Budget of the Agency. These co-ordinated research activities are normally implemented through Co-ordinated Research Projects (CRPs) that bring together research institutes in both developing and developed Member States to collaborate on the research topic of interest. The Agency may also respond to proposals from institutes for participation in the research activities by awarding individual contracts not related to a CRP. A small portion of available funds is used to finance individual projects, which deal with topics covered by the Agency's scientific programme. The Agency also supports several Doctoral CRPs. This new, optional type of CRP has been designed to strengthen promotion of research on nuclear technologies in developing Member States through pair building between agreement holders and contract holders. These CRPs include a PhD training programme at the contract holders' institutions. Three doctoral CRPs are currently being carried out by the Human Health programme. Further information on the Agency's co-ordinated research activities, including current information on CRPs and programme areas supported, information on policies and procedures and the administration of the activities is contained in the Agency's website at http://www-crp.iaea.org. The co-ordinated research activities reported in this document are conducted in support of the following Agency programmes: Nuclear Power; Nuclear Fuel Cycle and Material Technologies; Analysis for Sustainable

  15. Functional regulation of Q by microRNA172 and transcriptional co-repressor TOPLESS in controlling bread wheat spikelet density.

    Science.gov (United States)

    Liu, Pan; Liu, Jie; Dong, Huixue; Sun, Jiaqiang

    2018-02-01

    Bread wheat (Triticum aestivum) spike architecture is an important agronomic trait. The Q gene plays a key role in the domestication of bread wheat spike architecture. However, the regulatory mechanisms of Q expression and transcriptional activity remain largely unknown. In this study, we show that overexpression of bread wheat tae-miR172 caused a speltoid-like spike phenotype, reminiscent of that in wheat plants with the q gene. The reduction in Q transcript levels in the tae-miR172 overexpression transgenic bread wheat lines suggests that the Q expression can be suppressed by tae-miR172 in bread wheat. Indeed, our RACE analyses confirmed that the Q mRNA is targeted by tae-miR172 for cleavage. According to our analyses, the Q protein is localized in nucleus and confers transcriptional repression activity. Meanwhile, the Q protein could physically interact with the bread wheat transcriptional co-repressor TOPLESS (TaTPL). Specifically, the N-terminal ethylene-responsive element binding factor-associated amphiphilic repression (EAR) (LDLNVE) motif but not the C-terminal EAR (LDLDLR) motif of Q protein mediates its interaction with the CTLH motif of TaTPL. Moreover, we show that the N-terminal EAR motif of Q protein is also essentially required for the transcriptional repression activity of Q protein. Taken together, we reveal the functional regulation of Q protein by tae-miR172 and transcriptional co-repressor TaTPL in controlling the bread wheat spike architecture. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  16. Probing the active sites for CO dissociation on ruthenium nanoparticles

    DEFF Research Database (Denmark)

    Strebel, Christian Ejersbo; Murphy, Shane; Nielsen, Rasmus Munksgård

    2012-01-01

    affect the CO dissociation activity. The Ru nanoparticles were synthesized in a UHV chamber by gas-aggregation magnetron sputtering in the size range from 3 to 15 nm and the morphology was investigated in situ by scanning tunneling microscopy and ex situ by high resolution transmission electron...... microscopy. Surprisingly, it was found that larger particles were more active per surface area for CO dissociation. It is suggested that this is due to larger particles exposing a more rough surface than the smaller particles, giving rise to a higher relative amount of under-coordinated adsorption sites...... on the larger particles. The induced surface roughness is proposed to be a consequence of the growth processes in the gas-aggregation chamber....

  17. IGF-1 promotes angiogenesis in endothelial cells/adipose-derived stem cells co-culture system with activation of PI3K/Akt signal pathway.

    Science.gov (United States)

    Lin, Shiyu; Zhang, Qi; Shao, Xiaoru; Zhang, Tao; Xue, Changyue; Shi, Sirong; Zhao, Dan; Lin, Yunfeng

    2017-12-01

    The aim of this study was to investigate the role of insulin-like growth factor-1 (IGF-1) and crosstalk between endothelial cells (ECs) and adipose-derived stem cells (ASCs) in the process of angiogenesis. A three-dimensional collagen gel used to culture mouse ASCs and mouse ECs in vitro was established. The effects of angiogenesis after exposure to IGF-1 were observed by confocal laser scanning microscopy. Western blotting and qPCR were performed to elucidate the underlying mechanisms. IGF-1 treatment promoted the formation of vessel-like structures and the recruitment of ASCs in the three-dimensional collagen gel. The angiogenic genes and proteins in ECs were up-regulated by IGF-1 and in co-culture. Similar changes in the genes and in the proteins were detected in ASCs after exposure to IGF-1 and co-culture. p-Akt expression levels were high in ECs and ASCs after exposure to IGF-1 and co-culture. IGF-1 and co-culture between cells facilitate the process of angiogenesis via the PI3-kinase/Akt signalling pathway. In ECs, IGF-1 stimulates the expression of angiogenesis-related growth factors with the activation of the PI3-kinase/Akt signalling pathway. Co-cultured ECs exposed to excess VEGF-A and other angiogenesis-related growth factors para-secreted from ASCs exhibit high expression of angiogenesis-related genes and proteins. In ASCs, IGF-1 induces the recruitment and function of ASCs by up-regulating the expression of PDGFB, MMPs and α-SMA. Crosstalk with ECs further facilitates changes in ASCs. © 2017 John Wiley & Sons Ltd.

  18. Probing the Active Surface Sites for CO Reduction on Oxide-Derived Copper Electrocatalysts

    DEFF Research Database (Denmark)

    Verdaguer Casadevall, Arnau; Li, Christina W.; Johansson, Tobias Peter

    2015-01-01

    CO electroreduction activity on oxide-derived Cu (OD-Cu) was found to correlate with metastable surface features that bind CO strongly. OD-Cu electrodes prepared by H-2 reduction of Cu2O precursors reduce CO to acetate and ethanol with nearly 50% Faradaic efficiency at moderate overpotential. Tem...

  19. Catabolite regulation analysis of Escherichia coli for acetate overflow mechanism and co-consumption of multiple sugars based on systems biology approach using computer simulation.

    Science.gov (United States)

    Matsuoka, Yu; Shimizu, Kazuyuki

    2013-10-20

    It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. CATALYTIC WET PEROXIDE OXIDATION OF HYDROQUINONE WITH Co(II)/ACTIVE CARBON CATALYST LOADED IN STATIC BED

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Catalysts based on Co(II) supported on active carbon were prepared and loaded in static bed. The hydroquinone would be degraded completely after treated by Catalytic wet peroxide oxidation method with Co(II)/active carbon catalyst. After activate treatment, the active carbon was immerged in cobaltous nitrate solution, then put into a drying oven, Co(II) could be loaded on the micro-surface of carbon. Taking the static bed as the equipment, the absorption of active carbon and catalysis of Co(II) was used to reduce activation energy of hydroquinone. Thus hydroquinone could be drastically degraded and the effluent can be drained under the standard. Referring to Fenton reaction mechanism, experiment had been done to study the heterogeneous catalyzed oxidation mechanism of Co(II). The degradation rate of hydroquinone effluent could be achieved to 92% when treated in four columns at H2O2 concentration 10%, reaction temperature 40℃ , pH 5 and reaction time 2.5h.

  1. Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR Activity.

    Directory of Open Access Journals (Sweden)

    Firhan A Malik

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR attenuates sphingosine-1-phosphate (S1P signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK, establishing a potential feedback link. In Baby Hamster Kidney (BHK cells expressing wild-type human CFTR, S1P (1μmol/L attenuates forskolin-stimulated, CFTR-dependent iodide efflux. S1P's inhibitory effect is rapid (within 30 seconds, transient and correlates with CFTR serine residue 737 (S737 phosphorylation. Both S1P receptor antagonism (4μmol/L VPC 23019 and AMPK inhibition (80μmol/L Compound C or AMPK siRNA attenuate S1P-stimluated (i AMPK phosphorylation, (ii CFTR S737 phosphorylation and (iii CFTR activity inhibition. In BHK cells expressing the ΔF508 CFTR mutant (CFTRΔF508, the most common mutation causing cystic fibrosis, both S1P receptor antagonism and AMPK inhibition enhance CFTR activity, without instigating discernable correction. In summary, we demonstrate that S1P/AMPK signaling transiently attenuates CFTR activity. Since our previous work positions CFTR as a negative S1P signaling regulator, this signaling link may positively reinforce S1P signals. This discovery has clinical ramifications for the treatment of disease states associated with enhanced S1P signaling and/or deficient CFTR activity (e.g. cystic fibrosis, heart failure. S1P receptor/AMPK inhibition could synergistically enhance the efficacy of therapeutic strategies aiming to correct aberrant CFTR trafficking.

  2. Early bovine embryos regulate oviduct epithelial cell gene expression during in vitro co-culture.

    Science.gov (United States)

    Schmaltz-Panneau, Barbara; Cordova, Amanda; Dhorne-Pollet, Sophie; Hennequet-Antier, Christelle; Uzbekova, Sveltlana; Martinot, Emmanuelle; Doret, Sarah; Martin, Patrice; Mermillod, Pascal; Locatelli, Yann

    2014-10-01

    In mammals, the oviduct may participate to the regulation of early embryo development. In vitro co-culture of early bovine embryos with bovine oviduct epithelial cells (BOEC) has been largely used to mimic the maternal environment. However, the mechanisms of BOEC action have not been clearly elucidated yet. The aim of this study was to determine the response of BOEC cultures to the presence of developing bovine embryos. A 21,581-element bovine oligonucleotide array was used compare the gene expression profiles of confluent BOEC cultured for 8 days with or without embryos. This study revealed 34 differentially expressed genes (DEG). Of these 34 genes, IFI6, ISG15, MX1, IFI27, IFI44, RSAD2, IFITM1, EPSTI1, USP18, IFIT5, and STAT1 expression increased to the greatest extent due to the presence of embryos with a major impact on antiviral and immune response. Among the mRNAs at least 25 are already described as induced by interferons. In addition, transcript levels of new candidate genes involved in the regulation of transcription, modulation of the maternal immune system and endometrial remodeling were found to be increased. We selected 7 genes and confirmed their differential expression by quantitative RT-PCR. The immunofluorescence imaging of cellular localization of STAT1 protein in BOEC showed a nuclear translocation in the presence of embryos, suggesting the activation of interferon signaling pathway. This first systematic study of BOEC transcriptome changes in response to the presence of embryos in cattle provides some evidences that these cells are able to adapt their transcriptomic profile in response to embryo signaling. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. KCC2-mediated regulation of respiration-related rhythmic activity during postnatal development in mouse medulla oblongata.

    Science.gov (United States)

    Okabe, Akihito; Shimizu-Okabe, Chigusa; Arata, Akiko; Konishi, Shiro; Fukuda, Atsuo; Takayama, Chitoshi

    2015-03-19

    GABA acts as inhibitory neurotransmitter in the adult central nervous system but as excitatory neurotransmitter during early postnatal development. This shift in GABA's action from excitation to inhibition is caused by a decrease in intracellular chloride concentration ([Cl(-)]i), which in turn is caused by changes in the relative expression levels of the K(+)-Cl(-) co-transporter (KCC2) and the Na(+), K(+)-2Cl(-) co-transporter (NKCC1) proteins. Previous studies have used slices containing the medullary pre-Bötzinger complex (pre-BötC) to record respiration-related rhythmic activity (RRA) from the hypoglossal nucleus (12 N). The role of GABAergic transmission in the regulation of medullary RRA neonatally, however, is yet to be determined. Here, we examined how GABA and chloride co-transporters contribute to RRA during development in the 12 N where inspiratory neurons reside. We recorded extracellular RRA in medullary slices obtained from postnatal day (P) 0-7 mice. RRA was induced by soaking slices in artificial cerebrospinal fluid (aCSF) containing 8mM-K(+). Application of GABA significantly increased the frequency of RRA after P3, whereas application of a KCC2 blocker (R (+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-indenyl-5-yl)oxy]acetic acid (DIOA)) significantly decreased the frequency of RRA after P1. In addition, dense KCC2 immunolabeling was seen in the superior longitudinalis (SL) of the 12 N, which is responsible for retraction of the tongue, from P0 and P7. These results indicate that GABA administration can increase RRA frequency during the first week following birth. This in turn suggests that decreasing [Cl(-)]i levels caused by increasing KCC2 levels in the 12 N could play important roles in regulating the frequency of RRA during development. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. [Effect of elevated atmospheric CO2 on soil urease and phosphatase activities].

    Science.gov (United States)

    Chen, Lijun; Wu, Zhijie; Huang, Guohong; Zhou, Likai

    2002-10-01

    The response of soil urease and phosphatase activities at different rice growth stages to free air CO2 enrichment (FACE) was studied. The results showed that comparing with the ambient atmospheric CO2 concentration (370 mumol.mol-1), FACE (570 mumol.mol-1) significantly increased the urease activity of 0-5 cm soil layer at the vigorous growth stage of rice, whole that of 5-10 cm layer had no significant change during the whole growing season. Phosphatase activity of 0-5 cm and 5-10 cm soil layers significantly increased, and the peak increment was at the vigorous growth stage of rice.

  5. Integrating co-morbid depression and chronic physical disease management: identifying and resolving failures in self-regulation.

    Science.gov (United States)

    Detweiler-Bedell, Jerusha B; Friedman, Michael A; Leventhal, Howard; Miller, Ivan W; Leventhal, Elaine A

    2008-12-01

    Research suggests that treatments for depression among individuals with chronic physical disease do not improve disease outcomes significantly, and chronic disease management programs do not necessarily improve mood. For individuals experiencing co-morbid depression and chronic physical disease, demands on the self-regulation system are compounded, leading to a rapid depletion of self-regulatory resources. Because disease and depression management are not integrated, patients lack the understanding needed to prioritize self-regulatory goals in a way that makes disease and depression management synergistic. A framework in which the management of co-morbidity is considered alongside the management of either condition alone offers benefits to researchers and practitioners and may help improve clinical outcomes.

  6. Characterization of Co-Cultivation of Cyanobacteria on Growth, Productions of Polysaccharides and Extracellular Proteins, Nitrogenase Activity, and Photosynthetic Activity.

    Science.gov (United States)

    Xue, Chuizhao; Wang, Libo; Wu, Tong; Zhang, Shiping; Tang, Tao; Wang, Liang; Zhao, Quanyu; Sun, Yuhan

    2017-01-01

    Cyanobacteria as biofertilizers are benefit to reduce the use of chemical fertilizers and reestablish the ecological system in soil. In general, several strains of cyanobacteria were involved in the biofertilizers. The co-cultivation of cyanobacteria were characterized on growth profile, production of polysaccharides and extracellular proteins, nitrogenase activity, and photosynthetic activity for three selected N 2 -fixing cyanobacteria, Anabaena cylindrica (B1611 and F243) and Nostoc sp. (F280). After eight-day culture, the highest dry weights were obtained in F280 pure culture and co-cultivation of B1611 and F280. Higher production of extracellular proteins and cell-bonding polysaccharides (CPS) were observed in co-cultivations compared with pure culture. The highest released polysaccharides (RPS) contents were obtained in pure culture of F280 and co-cultivation of F280 and F243. Galactose and glucose were major components of CPS and RPS in all samples. Trehalose was a specific component of RPS in F280 pure culture. Based on the monosaccharide contents of CPS and RPS, F280 was the dominant species in the related treatments of co-cultivation. The nitrogenase activities in all treatments exhibited a sharp rise at the late stage while a significant decrease existed when three cyanobacteria strains were mixed. Photosynthetic activities for all treatments were determined with rapid light curve, and the related parameters were estimated.

  7. Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Yin [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Zhao, Shaomin [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States); School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069 (China); Song, Langying [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Wang, Manyuan [School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069 (China); Jiao, Kai, E-mail: kjiao@uab.edu [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2013-11-29

    Highlights: •SERTAD1 interacts with SMAD1. •Sertad1 is expressed in mouse embryonic hearts. •SERTAD1 is localized in both cytoplasm and nucleus of cardiomyocytes. •SERTAD1 enhances expression of BMP target cardiogenic genes as a SMAD1 co-activator. -- Abstract: Despite considerable advances in surgical repairing procedures, congenital heart diseases (CHDs) remain the leading noninfectious cause of infant morbidity and mortality. Understanding the molecular/genetic mechanisms underlying normal cardiogenesis will provide essential information for the development of novel diagnostic and therapeutic strategies against CHDs. BMP signaling plays complex roles in multiple cardiogenic processes in mammals. SMAD1 is a canonical nuclear mediator of BMP signaling, the activity of which is critically regulated through its interaction partners. We screened a mouse embryonic heart yeast two-hybrid library using Smad1 as bait and identified SERTAD1 as a novel interaction partner of SMAD1. SERTAD1 contains multiple potential functional domains, including two partially overlapping transactivation domains at the C terminus. The SERTAD1-SMAD1 interaction in vitro and in mammalian cells was further confirmed through biochemical assays. The expression of Sertad1 in developing hearts was demonstrated using RT-PCR, western blotting and in situ hybridization analyses. We also showed that SERTAD1 was localized in both the cytoplasm and nucleus of immortalized cardiomyocytes and primary embryonic cardiomyocyte cultures. The overexpression of SERTAD1 in cardiomyocytes not only enhanced the activity of two BMP reporters in a dose-dependent manner but also increased the expression of several known BMP/SMAD regulatory targets. Therefore, these data suggest that SERTAD1 acts as a SMAD1 transcriptional co-activator to promote the expression of BMP target genes during mouse cardiogenesis.

  8. Concomitant carboxylate and oxalate formation from the activation of CO{sub 2} by a thorium(III) complex

    Energy Technology Data Exchange (ETDEWEB)

    Formanuik, Alasdair; Ortu, Fabrizio; Mills, David P. [School of Chemistry, The University of Manchester (United Kingdom); Inman, Christopher J. [Department of Chemistry and Biochemistry, School of Life Sciences, University of Sussex, Brighton (United Kingdom); Kerridge, Andrew [Department of Chemistry, Lancaster University (United Kingdom); Castro, Ludovic; Maron, Laurent [LPCNO, CNRA et INSA, Universite Paul Sabatier, Toulouse (France)

    2016-12-12

    Improving our comprehension of diverse CO{sub 2} activation pathways is of vital importance for the widespread future utilization of this abundant greenhouse gas. CO{sub 2} activation by uranium(III) complexes is now relatively well understood, with oxo/carbonate formation predominating as CO{sub 2} is readily reduced to CO, but isolated thorium(III) CO{sub 2} activation is unprecedented. We show that the thorium(III) complex, [Th(Cp''){sub 3}] (1, Cp''={C_5H_3(SiMe_3)_2-1,3}), reacts with CO{sub 2} to give the mixed oxalate-carboxylate thorium(IV) complex [{Th(Cp'')_2[κ"2-O_2C{C_5H_3-3,3'-(SiMe_3)_2}]}{sub 2}(μ-κ{sup 2}:κ{sup 2}-C{sub 2}O{sub 4})] (3). The concomitant formation of oxalate and carboxylate is unique for CO{sub 2} activation, as in previous examples either reduction or insertion is favored to yield a single product. Therefore, thorium(III) CO{sub 2} activation can differ from better understood uranium(III) chemistry. (copyright 2016 The Authors. Published by Wiley-VCH Verlag GmbH and Co. KGaA.)

  9. Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

    Directory of Open Access Journals (Sweden)

    Dan Lv

    Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

  10. Activity of carbon supported Pt3Ru2 nanocatalyst in CO oxidation

    Directory of Open Access Journals (Sweden)

    KSENIJA DJ. POPOVIĆ

    2009-08-01

    Full Text Available The electrocatalytic activity of Pt3Ru2/C nanocatalyst toward the electro-oxidation of bulk CO was examined in acid and alkaline solution at ambient temperature using the thin-film, rotating disk electrode (RDE method. The catalyst was characterized by XRD analysis. The XRD pattern revealed that the Pt3Ru2/C catalyst consisted of two structures, i.e., Pt–Ru-fcc and Ru-hcp (a solid solution of Ru in Pt and a small amount of Ru or a solid solution of Pt in Ru. Electrocatalytic activities were measured by applying potentiodynamic and steady state techniques. The oxidation of CO on the Pt3Ru2/C catalyst was influenced by pH and anions from the supporting electrolytes. The Pt3Ru2/C was more active in alkaline than in acid solution, as well as in perchloric than in sulfuric acid. Comparison of CO oxidation on Pt3Ru2/C and Pt/C revealed that the Pt3Ru2/C was more active than Pt/C in acid solution, while both catalysts had a similar activity in alkaline solution.

  11. Metformin affects the features of a human hepatocellular cell line (HepG2) by regulating macrophage polarization in a co-culture microenviroment.

    Science.gov (United States)

    Chen, Miaojiao; Zhang, Jingjing; Hu, Fang; Liu, Shiping; Zhou, Zhiguang

    2015-11-01

    Accumulating evidence suggests an association between diabetes and cancer. Inflammation is a key event that underlies the pathological processes of the two diseases. Metformin displays anti-cancer effects, but the mechanism is not completely clear. This study investigated whether metformin regulated the microenvironment of macrophage polarization to affect the characteristics of HepG2 cells and the possible role of the Notch-signalling pathway. RAW264.7 macrophages were cultured alone or co-cultured with HepG2 cells and treated with metformin. We analysed classical (M1) and alternative (M2) gene expression in RAW264.7 cells using quantitative real-time polymerase chain reaction. Changes in mRNA and protein expressions of Notch signalling in both cell types were also detected using quantitative real-time polymerase chain reaction and Western-blotting analyses. The proliferation, apoptosis and migration of HepG2 cells were detected using Cell Titer 96 AQueous One Solution Cell Proliferation Assay (MTS) (Promega Corporation, Fitchburg, WI, USA), Annexin V-FITC/PI (7SeaPharmTech, Shanghai, China) and the cell scratch assay, respectively. Metformin induced single-cultured RAW264.7 macrophages with an M2 phenotype but attenuated the M2 macrophage differentiation and inhibited monocyte chemoattractant protein-1 (MCP-1) secretion in a co-culture system. The co-cultured group of metformin pretreatment activated Notch signalling in macrophages but repressed it inHepG2 cells. Co-culture also promoted the proliferation and migration of HepG2 cells. However, along with the enhanced apoptosis, the proliferation and the migration of HepG2 cells were remarkably inhibited in another co-culture system with metformin pretreatment. Metformin can skew RAW264.7 macrophages toward different phenotypes according to changes in the microenvironment, which may affect the inflammatory conditions mediated by macrophages, induce apoptosis and inhibit the proliferation and migration of HepG2

  12. Activation of peroxisome proliferator-activated receptor-α (PPARα) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

    International Nuclear Information System (INIS)

    Kimura, Rino; Takahashi, Nobuyuki; Murota, Kaeko; Yamada, Yuko; Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko; Moriyama, Tatsuya; Goto, Tsuyoshi; Kawada, Teruo

    2011-01-01

    Highlights: → PPARα activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. → PPARα activation also increased oxygen consumption rate and CO 2 production and decreased secretion of triglyceride and ApoB from Caco-2 cells. → Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO 2 production in small intestinal epithelial cells. → Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. → It suggested that intestinal lipid metabolism regulated by PPARα activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-α which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPARα activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPARα activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPARα agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO 2 and acid soluble metabolites in enterocytes. Moreover

  13. Activation cross section of 63Cu(n,α)60Co reaction

    International Nuclear Information System (INIS)

    Lu Hanlin; Zhao Wenrong; Yu Weixiang; Yuan Xialin

    1990-01-01

    The mechanical properties of copper during the irradiation with intensive neutron fluence rate are significant for the safe operation of D-T fusion power reactors. The cross sections measured by activation method show a large discrepancy from 36 to 54 mb in 14 MeV region. The cross sections of 69 Cu(n, α) 60 Co reaction were measured by activation method. Two irradiations were carried out at the Cockcroft-wallon and Van de Graaff accelerators of CIAE using T(d, n) 4 He reaction to produce neutrons. The activities of 24 Na and 60 Co γ-rays for monitor and sample foils were determined absolutely by a calibrated Ge(Li) detector system with an accuracy better than 1%. The present results are compared with the others

  14. Identification of evolutionarily conserved exons as regulated targets for the splicing activator tra2β in development.

    Directory of Open Access Journals (Sweden)

    Sushma Grellscheid

    2011-12-01

    Full Text Available Alternative splicing amplifies the information content of the genome, creating multiple mRNA isoforms from single genes. The evolutionarily conserved splicing activator Tra2β (Sfrs10 is essential for mouse embryogenesis and implicated in spermatogenesis. Here we find that Tra2β is up-regulated as the mitotic stem cell containing population of male germ cells differentiate into meiotic and post-meiotic cells. Using CLIP coupled to deep sequencing, we found that Tra2β binds a high frequency of exons and identified specific G/A rich motifs as frequent targets. Significantly, for the first time we have analysed the splicing effect of Sfrs10 depletion in vivo by generating a conditional neuronal-specific Sfrs10 knock-out mouse (Sfrs10(fl/fl; Nestin-Cre(tg/+. This mouse has defects in brain development and allowed correlation of genuine physiologically Tra2β regulated exons. These belonged to a novel class which were longer than average size and importantly needed multiple cooperative Tra2β binding sites for efficient splicing activation, thus explaining the observed splicing defects in the knockout mice. Regulated exons included a cassette exon which produces a meiotic isoform of the Nasp histone chaperone that helps monitor DNA double-strand breaks. We also found a previously uncharacterised poison exon identifying a new pathway of feedback control between vertebrate Tra2 proteins. Both Nasp-T and the Tra2a poison exon are evolutionarily conserved, suggesting they might control fundamental developmental processes. Tra2β protein isoforms lacking the RRM were able to activate specific target exons indicating an additional functional role as a splicing co-activator. Significantly the N-terminal RS1 domain conserved between flies and humans was essential for the splicing activator function of Tra2β. Versions of Tra2β lacking this N-terminal RS1 domain potently repressed the same target exons activated by full-length Tra2β protein.

  15. Regulation of the Osem gene by abscisic acid and the transcriptional activator VP1: analysis of cis-acting promoter elements required for regulation by abscisic acid and VP1.

    Science.gov (United States)

    Hattori, T; Terada, T; Hamasuna, S

    1995-06-01

    Osem, a rice gene homologous to the wheat Em gene, which encodes one of the late-embryogenesis abundant proteins was isolated. The gene was characterized with respect to control of transcription by abscisic acid (ABA) and the transcriptional activator VP1, which is involved in the ABA-regulated gene expression during late embryo-genesis. A fusion gene (Osem-GUS) consisting of the Osem promoter and the bacterial beta-glucuronidase (GUS) gene was constructed and tested in a transient expression system, using protoplasts derived from a suspension-cultured line of rice cells, for activation by ABA and by co-transfection with an expression vector (35S-Osvp1) for the rice VP1 (OSVP1) cDNA. The expression of Osem-GUS was strongly (40- to 150-fold) activated by externally applied ABA and by over-expression of (OS)VP1. The Osem promoter has three ACGTG-containing sequences, motif A, motif B and motif A', which resemble the abscisic acid-responsive element (ABRE) that was previously identified in the wheat Em and the rice Rab16. There is also a CATGCATG sequence, which is known as the Sph box and is shown to be essential for the regulation by VP1 of the maize anthocyanin regulatory gene C1. Focusing on these sequence elements, various mutant derivatives of the Osem promoter in the transient expression system were assayed. The analysis revealed that motif A functions not only as an ABRE but also as a sequence element required for the regulation by (OS)VP1.

  16. Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.

    Science.gov (United States)

    Lightfoot, J Timothy; DE Geus, Eco J C; Booth, Frank W; Bray, Molly S; DEN Hoed, Marcel; Kaprio, Jaakko; Kelly, Scott A; Pomp, Daniel; Saul, Michael C; Thomis, Martine A; Garland, Theodore; Bouchard, Claude

    2018-04-01

    Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity. Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

  17. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

    Science.gov (United States)

    Hertz, Rachel; Kalderon, Bella; Byk, Tamara; Berman, Ina; Za'tara, Ghadeer; Mayer, Raphael; Bar-Tana, Jacob

    2005-07-01

    Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

  18. Elevated CO2 causes changes in the photosynthetic apparatus of a toxic cyanobacterium, Cylindrospermopsis raciborskii.

    Science.gov (United States)

    Pierangelini, Mattia; Stojkovic, Slobodanka; Orr, Philip T; Beardall, John

    2014-07-15

    We studied the physiological acclimation of growth, photosynthesis and CO2-concentrating mechanism (CCM) in Cylindrospermopsis raciborskii exposed to low (present day; L-CO2) and high (1300ppm; H-CO2) pCO2. Results showed that under H-CO2 the cell specific division rate (μc) was higher and the CO2- and light-saturated photosynthetic rates (Vmax and Pmax) doubled. The cells' photosynthetic affinity for CO2 (K0.5CO2) was halved compared to L-CO2 cultures. However, no significant differences were found in dark respiration rates (Rd), pigment composition and light harvesting efficiency (α). In H-CO2 cells, non-photochemical quenching (NPQ), associated with state transitions of the electron transport chain (ETC), was negligible. Simultaneously, a reorganisation of PSII features including antenna connectivity (JconPSIIα), heterogeneity (PSIIα/β) and effective absorption cross sectional area (σPSIIα/β) was observed. In relation to different activities of the CCM, our findings suggest that for cells grown under H-CO2: (1) there is down-regulation of CCM activity; (2) the ability of cells to use the harvested light energy is altered; (3) the occurrence of state transitions is likely to be associated with changes of electron flow (cyclic vs linear) through the ETC; (4) changes in PSII characteristics are important in regulating state transitions. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. c-Abl Mediated Tyrosine Phosphorylation of Aha1 Activates Its Co-chaperone Function in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Diana M. Dunn

    2015-08-01

    Full Text Available The ability of Heat Shock Protein 90 (Hsp90 to hydrolyze ATP is essential for its chaperone function. The co-chaperone Aha1 stimulates Hsp90 ATPase activity, tailoring the chaperone function to specific “client” proteins. The intracellular signaling mechanisms directly regulating Aha1 association with Hsp90 remain unknown. Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1, promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity, enhances Hsp90 interaction with kinase clients, and compromises the chaperoning of non-kinase clients such as glucocorticoid receptor and CFTR. Suggesting a regulatory paradigm, we also find that Y223 phosphorylation leads to ubiquitination and degradation of hAha1 in the proteasome. Finally, pharmacologic inhibition of c-Abl prevents hAha1 interaction with Hsp90, thereby hypersensitizing cancer cells to Hsp90 inhibitors both in vitro and ex vivo.

  20. Synthesis of Co/N-HNTs composites and investigation on its catalytic activity for H{sub 2} generation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Dongcui; Cheng, Zhilin; Nan, Zhaodong, E-mail: zdnan@yzu.edu.cn

    2016-11-01

    Co/N-HNTs composites were synthesized via a one-pot solvothermal method, where amine functional halloysite nanotubes (N-HNTs) were used as support materials. Effects of sulfosuccinate sodium salt (AOT), an anionic surfactant, on morphology and dispersibility of Co particles anchored at the N-HNTs were studied. The dispersibility of the Co particles was promoted with the increase of the AOT concentration. The as-obtained composite was used as a catalyst to generate H{sub 2} gas by hydrolysis of NaBH{sub 4} solution. The catalytic activity of the composite was significantly enhanced than the pure Co and Co/graphene composite at the same experimental conditions reported by our laboratory, and the catalyst was conveniently separated from the solution by a magnet. The catalytic activity was enhanced when the dispersibility of the Co particles was improved at the surface of the N-HNTs and the Co content contained in the composite was lowed. At the same time, the Co particles anchored at the inner surface of the N-HNTs resulted in higher catalytic activity, where the Co particles may bond with nitrogen atoms. The activation energy for the hydrolysis of NaBH{sub 4} was calculated to be about 15.42 kJ mol{sup −1}. The catalyst can be continuously used for four times with about the same catalytic activity. - Highlights: • Co/N-HNTs composites are synthesized. • The dispersibility and morphology of the Co particles anchored at the N-HNTs are modified by AOT. • The composite shows higher catalytic activity for production H{sub 2} gas.

  1. A study of structure–activity relationships of commercial tertiary amines for post-combustion CO_2 capture

    International Nuclear Information System (INIS)

    Xiao, Min; Liu, Helei; Idem, Raphael; Tontiwachwuthikul, Paitoon; Liang, Zhiwu

    2016-01-01

    Highlights: • Ethyl group is beneficial for tertiary amines of CO_2 absorption. • The existence of side carbon chain may promote the activity of tertiary amine. • Hydroxyl group reduces the equilibrium CO_2 solubility, k_2 and pKa. • Heterocyclic structure decrease the equilibrium CO_2 solubility, k_2 and pKa. • Hydroxyl group results in higher CO_2 absorption heat. - Abstract: This work examined the relationship between the structure of various commercial tertiary amines and their activity in CO_2 absorption/desorption in terms of rate of CO_2 absorption, equilibrium CO_2 loading, pKa and heat of CO_2 absorption in order to establish possible guidelines for selection of tertiary amine components for amine blends. Results show that any electron donating group linked directly to the nitrogen atom increases their reactivity with CO_2. In addition, the presence of steric hindrance effect and good water solubility also show enhancements in activity. In contrast, the existence of a hydroxyl group leads to a decrease in all the activity of the tertiary amine. The heat of CO_2 absorption of tertiary amines, which is closely related to the regeneration energy, can be reduced by decreasing the number of hydroxyethyl groups or by positing the hydroxyl group at the proper carbon relative to the nitrogen atom.

  2. Iro/IRX transcription factors negatively regulate Dpp/TGF-β pathway activity during intestinal tumorigenesis.

    Science.gov (United States)

    Martorell, Òscar; Barriga, Francisco M; Merlos-Suárez, Anna; Stephan-Otto Attolini, Camille; Casanova, Jordi; Batlle, Eduard; Sancho, Elena; Casali, Andreu

    2014-11-01

    Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co-activation of these pathways in the adult Drosophila midgut induces "tumor-like" overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF-β acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX-family-protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF-β. IRX3 and IRX5 are upregulated in human adenomas, and their levels correlate inversely with the gene expression signature of response to TGF-β. In addition, Irx5 expression confers a growth advantage in the presence of TGF-β, but is selected against in its absence. Together, our results identify a set of Iro/IRX proteins as conserved negative regulators of Dpp/TGF-β activity. We propose that during the characteristic adenoma-to-carcinoma transition of human CRC, the activity of IRX proteins could reduce the sensitivity to the cytostatic effect of TGF-β, conferring a growth advantage to tumor cells prior to the acquisition of mutations in TGF-β pathway components. © 2014 The Authors.

  3. Structural Bases for the Regulation of CO Binding in the Archaeal Protoglobin from Methanosarcina acetivorans.

    Directory of Open Access Journals (Sweden)

    Lesley Tilleman

    Full Text Available Studies of CO ligand binding revealed that two protein states with different ligand affinities exist in the protoglobin from Methanosarcina acetivorans (in MaPgb*, residue Cys(E20101 was mutated to Ser. The switch between the two states occurs upon the ligation of MaPgb*. In this work, site-directed mutagenesis was used to explore the role of selected amino acids in ligand sensing and stabilization and in affecting the equilibrium between the "more reactive" and "less reactive" conformational states of MaPgb*. A combination of experimental data obtained from electronic and resonance Raman absorption spectra, CO ligand-binding kinetics, and X-ray crystallography was employed. Three amino acids were assigned a critical role: Trp(60B9, Tyr(61B10, and Phe(93E11. Trp(60B9 and Tyr(61B10 are involved in ligand stabilization in the distal heme pocket; the strength of their interaction was reflected by the spectra of the CO-ligated MaPgb* and by the CO dissociation rate constants. In contrast, Phe(93E11 is a key player in sensing the heme-bound ligand and promotes the rotation of the Trp(60B9 side chain, thus favoring ligand stabilization. Although the structural bases of the fast CO binding rate constant of MaPgb* are still unclear, Trp(60B9, Tyr(61B10, and Phe(93E11 play a role in regulating heme/ligand affinity.

  4. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (∼160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

  5. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (~160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

  6. Co-N-macrocyclic modified graphene with excellent electrocatalytic activity for lithium-thionyl chloride batteries

    International Nuclear Information System (INIS)

    Li, Bimei; Yuan, Zhongzhi; Xu, Ying; Liu, Jincheng

    2016-01-01

    Highlights: • A Co-N-graphene catalyst composed of CoN 4 -macrocyclic-like (CoN x ) structure is synthesized. • Co-N x -Graphene has effective electrocatalytic activity for Li/SOCl 2 batteries. • The storage stability of the catalyst is attributed to its insolubility in electrolyte. - Abstract: A mixture of cobalt phthalocyanine (CoPc) and graphene is thermally decomposed at 800 °C to synthesize a novel catalyst. Scanning electron microscopy (SEM) and transmission electron microscope (TEM) show that the catalyst retains the lamellar structure of graphene. X-ray diffraction (XRD) reveals that the catalyst is no longer composed of CoPc and high-resolution TEM (HRTEM), X-ray photoelectron spectra (XPS) prove that Co and N elements have entered the graphene molecular structure, thus forming a Co-N x -graphene (Co-N x -G) catalyst composed of a CoN 4 -macrocyclic-like structure. This catalyst serves as an excellent catalyst of thionyl chloride (SOCl 2 ) reduction. Cyclic voltammetry and battery discharge tests reveal that Co-N x -G-800 substantially increases the discharge voltage and capacity of a Li/SOCl 2 battery. Moreover, Co-N x -G-800 exhibits stable catalytic activity during battery storage. Ultraviolet–visible spectroscopy shows that CoPc is soluble in a SOCl 2 electrolyte solution, whereas Co-N x -G-800 is not, this characteristic contributes to the stable catalytic property of Co-N x -G.

  7. System to determine leaf photosynthetic activity by means of 14CO2

    International Nuclear Information System (INIS)

    Fernandez Gonzalez, J.

    1977-01-01

    A method to determine leaf photosynthetic activity is described. 14 CO 2 labeled air is produced from 14 CO 3 Ba and stored in a poliethylene balloon and supplied by means of an automatic dispenser to a perspex chamber inside of which is the leaf. (author) [es

  8. Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression.

    Science.gov (United States)

    Iser, David M; Avihingsanon, Anchalee; Wisedopas, Naruemon; Thompson, Alexander J; Boyd, Alison; Matthews, Gail V; Locarnini, Stephen A; Slavin, John; Desmond, Paul V; Lewin, Sharon R

    2011-01-14

    to determine if intrahepatic immune activation is increased in HIV-hepatitis B virus (HBV) co-infected patients compared to HBV mono-infected patients and whether this reduced following HBV-active antiretroviral therapy (ART) in HIV-HBV co-infected patients. : Case-control observational study. we examined liver biopsies for markers of T-cell and monocyte infiltration and activation, natural killer cells, hepatic stellate cell (HSC) activation (staining for alpha smooth muscle actin) and apoptosis [using terminal dUTP nick-end labelling (TUNEL)] in treatment-naive Asian HIV-HBV co-infected (n = 16) and HBV mono-infected patients matched for age and HBV e-antigen status (n = 16). Liver biopsies from a subset of co-infected patients (n = 15) were also compared prior to and following 48 weeks of HBV-active ART. HIV-HBV co-infected patients had a median CD4 T-cell count of 25 cells/microl and lower alanine aminotransferase levels than HBV mono-infected patients (P = 0.03). In HIV-HBV co-infected patients, hepatocyte apoptosis was increased (P = 0.04) but there were fewer intrahepatic CD4 and CD8 T cells (P < 0.001), lower activation of intrahepatic T cells, Kupffer cells and HSC (P = 0.002, 0.008 and < 0.001, respectively). Following ART, there was a significant decrease in intrahepatic HBsAg staining (P = 0.04) and Kupffer cell activation (P = 0.003). we found no evidence of increased intrahepatic mononuclear and HSC activation in this cohort of HIV-HBV co-infected individuals with advanced immune suppression. An increase in intra-hepatic apoptosis in HIV-HBV co-infected individuals may potentially contribute to accelerated fibrosis in this setting. 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  9. [Immune regulation activity and mechanism of Tibetan Kefir exopolysaccharide fractions].

    Science.gov (United States)

    Meng, Li; Zhang, Lanwei

    2009-12-01

    To investigate the effects and mechanism on immune regulation activity in mice of two Tibetan Kefir exoploysaccharides (EPS) with different molecular weight of 0.1 x 10(5) - 3 x 10(5) (fraction 1) and 1.8 x 10(3) (fraction 2). The immune regulation activity experiment was carried out in vitro based on the Functional Assessment Procedure and Test Methods of Health Food, which was issued by Ministry of Health of China. First, we treated mice subjects with EPS at doses of 40 mg/kg, 80 mg/kg, 120 mg/kg through ig. Then we detected the index of immune organs, the ability of antibody production (tested by HC50), activity of NK cell, delayed type hypersensitivity (DTH) and phagocytosis of macrophage in mice. Finally, we examined the expression of Erk protein in Macrophages by Western Blot assay. Fraction 1 could promote HC50, activity of NK cell and DTH in mice which low dose showed better. Fraction 2 could promote DTH, phagocytosis of macrophage which high dose showed better. The expression of Erk and COX-2 had the same trend with Phagocytic index. We verified the two fractions of Tibetan Kefir EPS could enhance immune functions in mice. Fraction 1 regulated immune function through NK cell and B cell while fraction 2 through macrophage cell and T cell. The effects to macrophage of Tibetan Kefir EPS in mice may realize through extra cellular signal-regulated kinase Erk pathway.

  10. Regulation of pokemon 1 activity by sumoylation.

    Science.gov (United States)

    Roh, Hee-Eun; Lee, Min-Nyung; Jeon, Bu-Nam; Choi, Won-Il; Kim, Yoo-Jin; Yu, Mi-Young; Hur, Man-Wook

    2007-01-01

    Pokemon 1 is a proto-oncogenic transcriptional regulator that contains a POZ domain at the N-terminus and four Kruppel-like zinc fingers at the C-terminus. Pokemon 1 plays an important role in adipogenesis, osteogenesis, oncogenesis, and transcription of NF-kB responsive genes. Recent reports have shown that biological activities of transcription factors are regulated by sumolylation. We investigated whether Pokemon 1 is post-translationally modified by sumoylation and whether the modification affects Pokemon 1's transcriptional properties. We found that Pokemon 1 is sumoylated in vitro and in vivo. Upon careful analysis of the amino acid sequence of Pokemon 1, we found ten potential sumoylation sites located at lysines 61, 354, 371, 379, 383, 396, 486, 487, 536 and 539. We mutated each of these amino acids into arginine and tested whether the mutation could affect the transcriptional properties of Pokemon 1 on the Pokemon 1 responsive genes, such as ADH5/FDH and pG5-FRE-Luc. Wild-type Pokemon 1 potently represses transcription of ADH5/FDH. Most of the mutants, however, were weaker transcription repressors and repressed transcription 1.3-3.3 fold less effective. Although potential sumoylation sites were located close to the DNA binding domain or the nuclear localization sequence, the mutations did not alter nuclear localization or DNA binding activity. In addition, on the pG5-FRE-Luc test promoter construct, ectopic SUMO-1 repressed transcription in the presence of Pokemon 1. The sumoylation target lysine residue at amino acid 61, which is located in the middle of the POZ-domain, is important because K61R mutation resulted in a much weaker molecular interaction with corepressors. Our data suggest that Pokemon 1's activity as a transcription factor may involve sumoylation, and that sumoylation might be important in the regulation of transcription by Pokemon 1.

  11. Co-operative approaches to regulation

    National Research Council Canada - National Science Library

    Huigen, Hans; Organisation for Economic Co-operation and Development

    1997-01-01

    ... from traditional command-and-control regulation. The case studies are organized according to a common framework designed to give information about the specific design and use of the alternative, positive and negative results, and more generally...

  12. Simultaneous Activation of Iron- and Thiol-Based Sensor-Regulator Systems by Redox-Active Compounds.

    Science.gov (United States)

    Lee, Kang-Lok; Yoo, Ji-Sun; Oh, Gyeong-Seok; Singh, Atul K; Roe, Jung-Hye

    2017-01-01

    Bacteria in natural habitats are exposed to myriad redox-active compounds (RACs), which include producers of reactive oxygen species (ROS) and reactive electrophile species (RES) that alkylate or oxidize thiols. RACs can induce oxidative stress in cells and activate response pathways by modulating the activity of sensitive regulators. However, the effect of a certain compound on the cell has been investigated primarily with respect to a specific regulatory pathway. Since a single compound can exert multiple chemical effects in the cell, its effect can be better understood by time-course monitoring of multiple sensitive regulatory pathways that the compound induces. We investigated the effect of representative RACs by monitoring the activity of three sensor-regulators in the model actinobacterium Streptomyces coelicolor ; SoxR that senses reactive compounds directly through oxidation of its [2Fe-2S] cluster, CatR/PerR that senses peroxides through bound iron, and an anti-sigma factor RsrA that senses RES via disulfide formation. The time course and magnitude of induction of their target transcripts were monitored to predict the chemical activities of each compound in S. coelicolor . Phenazine methosulfate (PMS) was found to be an effective RAC that directly activated SoxR and an effective ROS-producer that induced CatR/PerR with little thiol-perturbing activity. p -Benzoquinone was an effective RAC that directly activated SoxR, with slower ROS-producing activity, and an effective RES that induced the RsrA-SigR system. Plumbagin was an effective RAC that activated SoxR, an effective ROS-producer, and a less agile but effective RES. Diamide was an RES that effectively formed disulfides and a weak RAC that activated SoxR. Monobromobimane was a moderately effective RES and a slow producer of ROS. Interestingly, benzoquinone induced the SigR system by forming adducts on cysteine thiols in RsrA, revealing a new pathway to modulate RsrA activity. Overall, this study showed

  13. Abscisic acid-activated SNRK2 protein kinases function in the gene-regulation pathway of ABA signal transduction by phosphorylating ABA response element-binding factors.

    Science.gov (United States)

    Kobayashi, Yuhko; Murata, Michiharu; Minami, Hideyuki; Yamamoto, Shuhei; Kagaya, Yasuaki; Hobo, Tokunori; Yamamoto, Akiko; Hattori, Tsukaho

    2005-12-01

    The plant hormone abscisic acid (ABA) induces gene expression via the ABA-response element (ABRE) present in the promoters of ABA-regulated genes. A group of bZIP proteins have been identified as ABRE-binding factors (ABFs) that activate transcription through this cis element. A rice ABF, TRAB1, has been shown to be activated via ABA-dependent phosphorylation. While a large number of signalling factors have been identified that are involved in stomatal regulation by ABA, relatively less is known about the ABA-signalling pathway that leads to gene expression. We have shown recently that three members of the rice SnRK2 protein kinase family, SAPK8, SAPK9 and SAPK10, are activated by ABA signal as well as by hyperosmotic stress. Here we show that transient overexpression in cultured cell protoplasts of these ABA-activated SnRK2 protein kinases leads to the activation of an ABRE-regulated promoter, suggesting that these kinases are involved in the gene-regulation pathway of ABA signalling. We further show several lines of evidence that these ABA-activated SnRK2 protein kinases directly phosphorylate TRAB1 in response to ABA. Kinetic analysis of SAPK10 activation and TRAB1 phosphorylation indicated that the latter immediately followed the former. TRAB1 was found to be phosphorylated not only in response to ABA, but also in response to hyperosmotic stress, which was interpreted as the consequence of phosphorylation of TRAB1 by hyperosmotically activated SAPKs. Physical interaction between TRAB1 and SAPK10 in vivo was demonstrated by a co-immunoprecipitation experiment. Finally, TRAB1 was phosphorylated in vitro by the ABA-activated SnRK2 protein kinases at Ser102, which is phosphorylated in vivo in response to ABA and is critical for the activation function.

  14. Commission of energy regulation. 2004 activity report

    International Nuclear Information System (INIS)

    2004-01-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  15. Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

    Science.gov (United States)

    Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

    2015-01-01

    In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

  16. Phosphodiesterase activity is regulated by CC2D1A that is implicated in non-syndromic intellectual disability

    KAUST Repository

    Altawashi, Azza

    2013-07-04

    Background: Cyclic adenosine 3?5?-monophosphate (cAMP) is a key regulator of many cellular processes, including in the neuronal system, and its activity is tuned by Phosphodiesterase (PDE) activation. Further, the CC2D1A protein, consisting of N-Terminal containing four DM14 domains and C-terminal containing C2 domain, was shown to regulate the cAMP-PKA pathway. A human deletion mutation lacking the fourth DM14 and the adjacent C2 domain results in Non Syndromic Intellectual Disability (NSID) also referred to as Non Syndromic Mental Retardation (NSMR). Findings. Here we demonstrate that in Mouse Embryonic Fibroblasts (MEF) CC2D1A co-localizes with PDE4D in the cytosol before cAMP stimulation and on the periphery after stimulation, and that the movement to the periphery requires the full-length CC2D1A. In CC2D1A mouse mutant cells, the absence of three of the four DM14 domains abolishes migration of the complex to the periphery and causes constitutive phosphorylation of PDE4D Serine 126 (Sssup126esup) via the cAMP-dependent protein kinase A (PKA) resulting in PDE4D hyperactivity. Suppressing PDE4D activity with Rolipram in turn restores the down-stream phosphorylation of the "cAMP response element-binding protein" (CREB) that is defective in mouse mutant cells. Conclusion: Our findings suggest that CC2D1A is a novel regulator of PDE4D. CC2D1A interacts directly with PDE4D regulating its activity and thereby fine-tuning cAMP-dependent downstream signaling. Based on our in vitro evidence we propose a model which links CC2D1A structure and function to cAMP homeostasis thereby affecting CREB phosphorylation. We speculate that CC2D1A and/or PDE4D may be promising targets for therapeutic interventions in many disorders with impaired PDE4D function such as NSID. 2013 Al-Tawashi and Gehring; licensee BioMed Central Ltd.

  17. NMR characterization of altered lignins extracted from tobacco plants down-regulated for lignification enzymes cinnamylalcohol dehydrogenase and cinnamoyl-CoA reductase.

    Science.gov (United States)

    Ralph, J; Hatfield, R D; Piquemal, J; Yahiaoui, N; Pean, M; Lapierre, C; Boudet, A M

    1998-10-27

    Homologous antisense constructs were used to down-regulate tobacco cinnamyl-alcohol dehydrogenase (CAD; EC 1.1.1.195) and cinnamoyl-CoA reductase (CCR; EC 1.2.1.44) activities in the lignin monomer biosynthetic pathway. CCR converts activated cinnamic acids (hydroxycinnamoyl-SCoAs) to cinnamaldehydes; cinnamaldehydes are then reduced to cinnamyl alcohols by CAD. The transformations caused the incorporation of nontraditional components into the extractable tobacco lignins, as evidenced by NMR. Isolated lignin of antisense-CAD tobacco contained fewer coniferyl and sinapyl alcohol-derived units that were compensated for by elevated levels of benzaldehydes and cinnamaldehydes. Products from radical coupling of cinnamaldehydes, particularly sinapaldehyde, which were barely discernible in normal tobacco, were major components of the antisense-CAD tobacco lignin. Lignin content was reduced in antisense-CCR tobacco, which displayed a markedly reduced vigor. That lignin contained fewer coniferyl alcohol-derived units and significant levels of tyramine ferulate. Tyramine ferulate is a sink for the anticipated build-up of feruloyl-SCoA, and may be up-regulated in response to a deficit of coniferyl alcohol. Although it is not yet clear whether the modified lignins are true structural components of the cell wall, the findings provide further indications of the metabolic plasticity of plant lignification. An ability to produce lignin from alternative monomers would open new avenues for manipulation of lignin by genetic biotechnologies.

  18. Improving the Way State and Federal Co-Regulators Communicate about Risk

    International Nuclear Information System (INIS)

    Easton, E.; Janairo, L.R.

    2009-01-01

    This paper explores risk communications concepts that could be used by Federal and state governments to help the public understand how government officials rely on risk analysis and management to ensure that shipments of spent fuel and other radioactive wastes take place in a safe, secure manner that merits public confidence. A key focus in the communication concepts put forward in the paper is the relationship between understanding and validating the public's concerns and explaining how those concerns are being addressed by current safety requirements and practices. The authors will recommend best practices to state and Federal officials that have the responsibility for communicating with the public about radioactive waste transportation. The paper will also suggest ways to bring these state and federal co-regulators together to communicate more effectively and to speak with one voice on the issue of shipment safety. (authors)

  19. Effect of elevated CO2 on degradation of azoxystrobin and soil microbial activity in rice soil.

    Science.gov (United States)

    Manna, Suman; Singh, Neera; Singh, V P

    2013-04-01

    An experiment was conducted in open-top chambers (OTC) to study the effect of elevated CO2 (580 ± 20 μmol mol(-1)) on azoxystrobin degradation and soil microbial activities. Results indicated that elevated CO2 did not have any significant effect on the persistence of azoxystrobin in rice-planted soil. The half-life values for the azoxystrobin in rice soils were 20.3 days in control (rice grown at ambient CO2 outdoors), 19.3 days in rice grown under ambient CO2 atmosphere in OTC, and 17.5 days in rice grown under elevated CO2 atmosphere in OTC. Azoxystrobin acid was recovered as the only metabolite of azoxystrobin, but it did not accumulate in the soil/water and was further metabolized. Elevated CO2 enhanced soil microbial biomass (MBC) and alkaline phosphatase activity of soil. Compared with rice grown at ambient CO2 (both outdoors and in OTC), the soil MBC at elevated CO2 increased by twofold. Elevated CO2 did not affect dehydrogenase, fluorescein diacetate, and acid phosphatase activity. Azoxystrobin application to soils, both ambient and elevated CO2, inhibited alkaline phosphates activity, while no effect was observed on other enzymes. Slight increase (1.8-2 °C) in temperature inside OTC did not affect microbial parameters, as similar activities were recorded in rice grown outdoors and in OTC at ambient CO2. Higher MBC in soil at elevated CO2 could be attributed to increased carbon availability in the rhizosphere via plant metabolism and root secretion; however, it did not significantly increase azoxystrobin degradation, suggesting that pesticide degradation was not the result of soil MBC alone. Study suggested that increased CO2 levels following global warming might not adversely affect azoxystrobin degradation. However, global warming is a continuous and cumulative process, therefore, long-term studies are necessary to get more realistic assessment of global warming on fate of pesticide.

  20. The SUD1 gene encodes a putative E3 ubiquitin ligase and is a positive regulator of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in Arabidopsis.

    Science.gov (United States)

    Doblas, Verónica G; Amorim-Silva, Vítor; Posé, David; Rosado, Abel; Esteban, Alicia; Arró, Montserrat; Azevedo, Herlander; Bombarely, Aureliano; Borsani, Omar; Valpuesta, Victoriano; Ferrer, Albert; Tavares, Rui M; Botella, Miguel A

    2013-02-01

    The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the major rate-limiting step of the mevalonic acid (MVA) pathway from which sterols and other isoprenoids are synthesized. In contrast with our extensive knowledge of the regulation of HMGR in yeast and animals, little is known about this process in plants. To identify regulatory components of the MVA pathway in plants, we performed a genetic screen for second-site suppressor mutations of the Arabidopsis thaliana highly drought-sensitive drought hypersensitive2 (dry2) mutant that shows decreased squalene epoxidase activity. We show that mutations in SUPPRESSOR OF DRY2 DEFECTS1 (SUD1) gene recover most developmental defects in dry2 through changes in HMGR activity. SUD1 encodes a putative E3 ubiquitin ligase that shows sequence and structural similarity to yeast Degradation of α factor (Doα10) and human TEB4, components of the endoplasmic reticulum-associated degradation C (ERAD-C) pathway. While in yeast and animals, the alternative ERAD-L/ERAD-M pathway regulates HMGR activity by controlling protein stability, SUD1 regulates HMGR activity without apparent changes in protein content. These results highlight similarities, as well as important mechanistic differences, among the components involved in HMGR regulation in plants, yeast, and animals.

  1. Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity.

    Science.gov (United States)

    Sahu, Bhanu P; Hazarika, Hemanga; Bharadwaj, Rituraj; Loying, Pojul; Baishya, Rinku; Dash, Suvakanta; Das, Malay K

    2016-08-01

    A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

  2. Monocyte to macrophage differentiation-associated (MMD) positively regulates ERK and Akt activation and TNF-α and NO production in macrophages.

    Science.gov (United States)

    Liu, Qiang; Zheng, Jin; Yin, Dan-Dan; Xiang, Jie; He, Fei; Wang, Yao-Chun; Liang, Liang; Qin, Hong-Yan; Liu, Li; Liang, Ying-Min; Han, Hua

    2012-05-01

    Macrophage activation is modulated by both environmental cues and endogenous programs. In the present study, we investigated the role of a PAQR family protein, monocyte to macrophage differentiation-associated (MMD), in macrophage activation and unveiled its underlying molecular mechanism. Our results showed that while MMD expression could be detected in all tissues examined, its expression level is significantly up-regulated upon monocyte differentiation. Within cells, EGFP-MMD fusion protein could be co-localized to endoplasmic reticulum, mitochondria, Golgi apparatus, but not lysosomes and cytoplasm. MMD expression is up-regulated in macrophages after LPS stimulation, and this might be modulated by RBP-J, the critical transcription factor of Notch signaling. Overexpression of MMD in macrophages increased the production of TNF-α and NO upon LPS stimulation. We found that MMD overexpression enhanced ERK1/2 and Akt phosphorylation in macrophages after LPS stimulation. Blocking Erk or Akt by pharmacological agent reduced TNF-α or NO production in MMD-overexpressing macrophages, respectively. These results suggested that MMD modulates TNF-α and NO production in macrophages, and this process might involves Erk or Akt.

  3. Neural activity to a partner's facial expression predicts self-regulation after conflict

    Science.gov (United States)

    Hooker, Christine I.; Gyurak, Anett; Verosky, Sara; Miyakawa, Asako; Ayduk, Özlem

    2009-01-01

    Introduction Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to the regulation of emotional experience in response to lab-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk-factor for mood and behavior problems after an interpersonal stressor. However, it remains unclear whether LPFC activity to a lab-based affective challenge predicts self-regulation in real-life. Method We investigated whether LPFC activity to a lab-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During an fMRI scan, healthy, adult participants in committed, dating relationships (N = 27) viewed positive, negative, and neutral facial expressions of their partners. In an online daily-diary, participants reported conflict occurrence, level of negative mood, rumination, and substance-use. Results LPFC activity in response to the lab-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to the change in mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted the change in mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance-use. Conclusions Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor. PMID:20004365

  4. Neural activity to a partner's facial expression predicts self-regulation after conflict.

    Science.gov (United States)

    Hooker, Christine I; Gyurak, Anett; Verosky, Sara C; Miyakawa, Asako; Ayduk, Ozlem

    2010-03-01

    Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to emotion regulation in response to laboratory-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk factor for mood and behavior problems after an interpersonal conflict. However, it remains unclear whether LPFC activity to a laboratory-based affective challenge predicts self-regulation in real life. We investigated whether LPFC activity to a laboratory-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During a functional magnetic resonance imaging scan, healthy, adult participants in committed relationships (n = 27) viewed positive, negative, and neutral facial expressions of their partners. In a three-week online daily diary, participants reported conflict occurrence, level of negative mood, rumination, and substance use. LPFC activity in response to the laboratory-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance use. Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. In situ characterization of cofacial Co(IV) centers in Co4O4 cubane: Modeling the high-valent active site in oxygen-evolving catalysts.

    Science.gov (United States)

    Brodsky, Casey N; Hadt, Ryan G; Hayes, Dugan; Reinhart, Benjamin J; Li, Nancy; Chen, Lin X; Nocera, Daniel G

    2017-04-11

    The Co 4 O 4 cubane is a representative structural model of oxidic cobalt oxygen-evolving catalysts (Co-OECs). The Co-OECs are active when residing at two oxidation levels above an all-Co(III) resting state. This doubly oxidized Co(IV) 2 state may be captured in a Co(III) 2 (IV) 2 cubane. We demonstrate that the Co(III) 2 (IV) 2 cubane may be electrochemically generated and the electronic properties of this unique high-valent state may be probed by in situ spectroscopy. Intervalence charge-transfer (IVCT) bands in the near-IR are observed for the Co(III) 2 (IV) 2 cubane, and spectroscopic analysis together with electrochemical kinetics measurements reveal a larger reorganization energy and a smaller electron transfer rate constant for the doubly versus singly oxidized cubane. Spectroelectrochemical X-ray absorption data further reveal systematic spectral changes with successive oxidations from the cubane resting state. Electronic structure calculations correlated to experimental data suggest that this state is best represented as a localized, antiferromagnetically coupled Co(IV) 2 dimer. The exchange coupling in the cofacial Co(IV) 2 site allows for parallels to be drawn between the electronic structure of the Co 4 O 4 cubane model system and the high-valent active site of the Co-OEC, with specific emphasis on the manifestation of a doubly oxidized Co(IV) 2 center on O-O bond formation.

  6. Motivation and Behavioral Regulation of Physical Activity in Middle School Students.

    Science.gov (United States)

    Dishman, Rod K; McIver, Kerry L; Dowda, Marsha; Saunders, Ruth P; Pate, Russell R

    2015-09-01

    This study aimed to examine whether intrinsic motivation and behavioral self-regulation are related to physical activity during middle school. Structural equation modeling was applied in cross-sectional and longitudinal tests of self-determination theory. Consistent with theory, hypothesized relations among variables were supported. Integrated regulation and intrinsic motivation were most strongly correlated with moderate-to-vigorous physical activity measured by an accelerometer. Results were independent of a measure of biological maturity. Construct validity and equivalence of measures were confirmed longitudinally between the sixth and seventh grades and between boys and girls, non-Hispanic Black and White children and overweight and normal-weight students. Measures of autonomous motivation (identified, integrated, and intrinsic) were more strongly related to physical activity in the seventh grade than measures of controlled motivation (external and introjected), implying that physical activity became more intrinsically motivating for some girls and boys as they moved through middle school. Nonetheless, change in introjected regulation was related to change in physical activity in the seventh grade, suggesting that internalized social pressures, which can be detrimental to sustained activity and well-being, also became motivating. These results encourage longer prospective studies during childhood and adolescence to clarify how controlled and autonomous motivations for physical activity develop and whether they respond to interventions designed to increase physical activity.

  7. Motivation and Behavioral Regulation of Physical Activity in Middle-School Students

    Science.gov (United States)

    Dishman, Rod K.; McIver, Kerry L; Dowda, Marsha; Saunders, Ruth P.; Pate, Russell R.

    2015-01-01

    Purpose To examine whether intrinsic motivation and behavioral self-regulation are related to physical activity during middle school. Method Structural equation modeling was applied in cross-sectional and longitudinal tests of self-determination theory. Results Consistent with theory, hypothesized relationships among variables were supported. Integrated regulation and intrinsic motivation were most strongly correlated with moderate-to-vigorous physical activity measured by an accelerometer. Results were independent of a measure of biological maturity. Construct validity and equivalence of measures was confirmed longitudinally between 6th and 7th grades and between boys and girls, non-Hispanic black and white children and overweight and normal weight students. Conclusions Measures of autonomous motivation (identified, integrated, and intrinsic) were more strongly related to physical activity in the 7th grade than measures of controlled motivation (external and introjected), implying that physical activity became more intrinsically motivating for some girls and boys as they moved through middle school. Nonetheless, introjected regulation was related to physical activity in 7th grade, suggesting that internalized social pressures, which can be detrimental to sustained activity and well-being, also became motivating. These results encourage longer prospective studies during childhood and adolescence to clarify how controlled and autonomous motivations for physical activity develop and whether they respond to interventions designed to increase physical activity. PMID:25628178

  8. DEPTOR regulates vascular endothelial cell activation and proinflammatory and angiogenic responses.

    Science.gov (United States)

    Bruneau, Sarah; Nakayama, Hironao; Woda, Craig B; Flynn, Evelyn A; Briscoe, David M

    2013-09-05

    The maintenance of normal tissue homeostasis and the prevention of chronic inflammatory disease are dependent on the active process of inflammation resolution. In endothelial cells (ECs), proinflammation results from the activation of intracellular signaling responses and/or the inhibition of endogenous regulatory/pro-resolution signaling networks that, to date, are poorly defined. In this study, we find that DEP domain containing mTOR interacting protein (DEPTOR) is expressed in different microvascular ECs in vitro and in vivo, and using a small interfering RNA (siRNA) knockdown approach, we find that it regulates mammalian target of rapamycin complex 1 (mTORC1), extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 1 activation in part through independent mechanisms. Moreover, using limited gene arrays, we observed that DEPTOR regulates EC activation including mRNA expression of the T-cell chemoattractant chemokines CXCL9, CXCL10, CXCL11, CX3CL1, CCL5, and CCL20 and the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (P < .05). DEPTOR siRNA-transfected ECs also bound increased numbers of peripheral blood mononuclear cells (P < .005) and CD3+ T cells (P < .005) in adhesion assays in vitro and had increased migration and angiogenic responses in spheroid sprouting (P < .01) and wound healing (P < .01) assays. Collectively, these findings define DEPTOR as a critical upstream regulator of EC activation responses and suggest that it plays an important role in endogenous mechanisms of anti-inflammation and pro-resolution.

  9. BAFF induces spleen CD4+ T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

    International Nuclear Information System (INIS)

    Ji, Fang; Chen, Rongjing; Liu, Baojun; Zhang, Xiaoping; Han, Junli; Wang, Haining; Shen, Gang; Tao, Jiang

    2012-01-01

    Highlights: ► Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4 + T cells. ► Carrying out siRNA technology to study FOXO3A protein function. ► Helpful to understand the T cell especially CD4 + T cell‘s role in immunological reaction. -- Abstract: The TNF ligand family member “B cell-activating factor belonging to the TNF family” (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4 + spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4 + T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4 + spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4 + T cell proliferation.

  10. Boron transport in plants: co-ordinated regulation of transporters

    Science.gov (United States)

    Miwa, Kyoko; Fujiwara, Toru

    2010-01-01

    Background The essentiality of boron (B) for plant growth was established >85 years ago. In the last decade, it has been revealed that one of the physiological roles of B is cross-linking the pectic polysaccharide rhamnogalacturonan II in primary cell walls. Borate cross-linking of pectic networks serves both for physical strength of cell walls and for cell adhesion. On the other hand, high concentrations of B are toxic to plant growth. To avoid deficiency and toxicity problems, it is important for plants to maintain their tissue B concentrations within an optimum range by regulating transport processes. Boron transport was long believed to be a passive, unregulated process, but the identification of B transporters has suggested that plants sense and respond to the B conditions and regulate transporters to maintain B homeostasis. Scope Transporters responsible for efficient B uptake by roots, xylem loading and B distribution among leaves have been described. These transporters are required under B limitation for efficient acquisition and utilization of B. Transporters important for tolerating high B levels in the environment have also been identified, and these transporters export B from roots back to the soil. Two types of transporters are involved in these processes: NIPs (nodulin-26-like intrinsic proteins), boric acid channels, and BORs, B exporters. It is demonstrated that the expression of genes encoding these transporters is finely regulated in response to B availability in the environment to ensure tissue B homeostasis. Furthermore, plants tolerant to stress produced by low B or high B in the environment can be generated through altered expression of these transporters. Conclusions The identification of the first B transporter led to the discovery that B transport was a process mediated not only by passive diffusion but also by transporters whose activity was regulated in response to B conditions. Now it is evident that plants sense internal and external B

  11. Effects of 200 Gy 60Co-γ Radiation on the Regulation of Antioxidant Enzymes, Hsp70 Genes, and Serum Molecules of Plutella xylostella (Linnaeus).

    Science.gov (United States)

    Li, Xiaoxue; Luo, Lingyan; Karthi, Sengodan; Zhang, Ke; Luo, Jianjun; Hu, Qiongbo; Weng, Qunfang

    2018-04-26

    The diamondback moth, Plutella xylostella (Linnaeus), is one of the notorious pests causing substantial loses to many cruciferous vegetables across the nations. The effects of 60 Co-γ radiation on physiology of P. xylostella were investigated and the results displayed that 200 Gy irradiation significantly alters the antioxidant enzyme regulation in six-day-old male pupae of P. xylostella . First, in our research, we detected Oxidase system and stress response mechanism of irradiated pupae, the results displayed that 200 Gy irradiation significantly alters the antioxidant enzyme regulation in six-day-old male pupae of P. xylostella . The levels of superoxide dismutase (SOD) and catalase (CAT) were increased significantly in contrast the level of peroxidase (POD) and glutathione S-transferase (GST) were decreased in 12⁻24 h post-treatment. The heat shock proteins (Hsps) gene expression level was significant increasing, maximum > 2-folds upregulation of genes were observed in peak. However, they also had a trend of gradual recovery with development. Second, we detected the testis lactate dehydrogenase (LDH) and acid phosphatase (ACP) activity found that in male adults testis they increased significantly than control during its development. Thus the present research investigation highlights that the 60 Co-γ radiation treatments alters the physiological development of diamondback moth. The results showed that 200 Gy dosage resulted in stress damage to the body and reproductive system of the diamondback moth.

  12. Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the iron-sulfur cluster assembly protein IscU.

    Science.gov (United States)

    Silberg, Jonathan J; Tapley, Tim L; Hoff, Kevin G; Vickery, Larry E

    2004-12-24

    The ATPase activity of HscA, a specialized hsp70 molecular chaperone from Escherichia coli, is regulated by the iron-sulfur cluster assembly protein IscU and the J-type co-chaperone HscB. IscU behaves as a substrate for HscA, and HscB enhances the binding of IscU to HscA. To better understand the mechanism by which HscB and IscU regulate HscA, we examined binding of HscB to the different conformational states of HscA and the effects of HscB and IscU on the kinetics of the individual steps of the HscA ATPase reaction cycle. Affinity sensor studies revealed that whereas IscU binds both ADP (R-state) and ATP (T-state) HscA complexes, HscB interacts only with an ATP-bound state. Studies of ATPase activity under single-turnover and rapid mixing conditions showed that both IscU and HscB interact with the low peptide affinity T-state of HscA (HscA++.ATP) and that both modestly accelerate (3-10-fold) the rate-determining steps in the HscA reaction cycle, k(hyd) and k(T-->R). When present together, IscU and HscB synergistically stimulate both k(hyd) (approximately = 500-fold) and k(T-->R) (approximately = 60-fold), leading to enhanced formation of the HscA.ADP-IscU complex (substrate capture). Following ADP/ATP exchange, IscU also stimulates k(R-->T) (approximately = 50-fold) and thereby accelerates the rate at which the low peptide affinity HscA++.ATP T-state is regenerated. Because HscA nucleotide exchange is fast, the overall rate of the chaperone cycle in vivo will be determined by the availability of the IscU-HscB substrate-co-chaperone complex.

  13. Regulation of mitogen-activated protein kinase pathways by the plasma membrane Na+/H+ exchanger, NHE1

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Darborg, Barbara Vasek; Rentsch, Maria Louise

    2006-01-01

    activity is regulated by a three-tiered phosphorelay system, which is in turn regulated by a complex network of signaling events and scaffolding proteins. The ubiquitous plasma membrane Na(+)/H(+) exchanger NHE1 is activated by, and implicated in, the physiological/pathophysiological responses to many...... of the same stimuli that modulate MAPK activity. While under some conditions, NHE1 is regulated by MAPKs, a number of studies have, conversely, implicated NHE1 in the regulation of MAPK activity. Here, we discuss the current evidence indicating the involvement of NHE1 in MAPK regulation, the mechanisms...

  14. Emotion regulation strategies: procedure modeling of J. Gross and cultural activity approach

    Directory of Open Access Journals (Sweden)

    Elena I. Pervichko

    2015-03-01

    Full Text Available The first part of this paper argued the desirability of structural-dynamic model of emotion regulation in the theoretical and methodological framework of cultural activity paradigm with the construction of a psychologically-based typology of emotion regulation strategies in norm and pathology, and also psychological mechanisms enabling the regulation of emotions. This conclusion was based on the analysis of the basic concepts and paradigms in which the issue of emotion regulation is studied: cognitive and psychoanalytic approaches, concept and emotional development of emotional intelligence, cultural activity approach. The paper considers the procedure model of emotion regulation by J. Gross, identifies emotion regulation strategies and evaluates their effectiveness. The possibilities and limitations of the model. Based on the review of the today research the conclusion is arrived at that the existing labels on a wide range of regulatory strategies remain an open issue.The author’s definition of emotion regulation is drawn. Emotion regulation is deemed as a set of mental processes, psychological mechanisms and regulatory strategies that people use to preserve the capacity for productive activities in a situation of emotional stress; to ensure optimal impulse control and emotions; to maintain the excitement at the optimum level. The second part of this paper provides the general description of emotion regulation strategies, the approach to their typology, the psychological mechanisms of emotion regulation that lie in the basis of this typology, i.e. the main elements of the structural-dynamic model of emotion regulation. The work shows theoretical and methodological efficacy of empirical significance of signs and symbols and also personal reflection. The diagnostic system to allow empirically identify a wide range of emotion regulation strategies is suggested. The psychological mechanisms used by the subject to solve the problem of emotional

  15. Combustion synthesis and catalytic activity of LaCoO{sub 3} for HMX thermal decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Zhi-Xian; Chi, Ying-Nan [Department of Chemistry, Institute for Chemical Physics, Beijing Institute of Technology (China); Hu, Chang-Wen [State Key Laboratory of Explosion Science, Technology Beijing Institute of Technology, Beijing (China); Liu, Hai-Yan [Department of Chemistry, Science Institute, North China University, Taiyuan, Shanxi (China)

    2009-10-15

    Perovskite-type LaCoO{sub 3} was prepared by stearic acid solution combustion method and characterized by XRD, DSC-TG, and XPS techniques. The catalytic activities of LaCoO{sub 3} for HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) thermal decomposition were investigated. The as-prepared LaCoO{sub 3} shows higher activity than the calcined one. This could be due to higher concentration of surface-adsorbed oxygen and hydroxyl species as well as higher BET surface area of the as-prepared LaCoO{sub 3}. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  16. Catalytic activity trends of CO oxidation – A DFT study

    DEFF Research Database (Denmark)

    Jiang, Tao

    theoretical study of CO oxidation with experimental studies. The latter shows promoted catalytic activity when gold particle size decreases to 5 nm. Oxidizing CO by N2O was found to involve a CO␣O transition state, with atomic O adsorbed on the gold B5 sites and CO on the corners. On the other hand, CO...... and experiment were found to be the same. The experiment findings are in good agreement with our theoretical calculations. The second part of the thesis focuses on improving the convergence property of Quasi-Newton algorithm. The eigenvalues of the Hessian matrix of 54 atoms bulk Cu model are calculated......, and the sizes of eigenvalues follow power-law distribution. It is found that the anharmonicity of the weak modes lead to poor Newton step and poor Hessian update in BFGS type Quasi-Newton algorithm, which slow down the geometry optimization. Line search that fulfills Wolff conditions is then applied to improve...

  17. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    Science.gov (United States)

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Effect of elevated CO2 on chlorpyriphos degradation and soil microbial activities in tropical rice soil.

    Science.gov (United States)

    Adak, Totan; Munda, Sushmita; Kumar, Upendra; Berliner, J; Pokhare, Somnath S; Jambhulkar, N N; Jena, M

    2016-02-01

    Impact of elevated CO2 on chlorpyriphos degradation, microbial biomass carbon, and enzymatic activities in rice soil was investigated. Rice (variety Naveen, Indica type) was grown under four conditions, namely, chambered control, elevated CO2 (550 ppm), elevated CO2 (700 ppm) in open-top chambers and open field. Chlorpyriphos was sprayed at 500 g a.i. ha(-1) at maximum tillering stage. Chlorpyriphos degraded rapidly from rice soils, and 88.4% of initially applied chlorpyriphos was lost from the rice soil maintained under elevated CO2 (700 ppm) by day 5 of spray, whereas the loss was 80.7% from open field rice soil. Half-life values of chlorpyriphos under different conditions ranged from 2.4 to 1.7 days with minimum half-life recorded with two elevated CO2 treatments. Increased CO2 concentration led to increase in temperature (1.2 to 1.8 °C) that played a critical role in chlorpyriphos persistence. Microbial biomass carbon and soil enzymatic activities specifically, dehydrogenase, fluorescien diacetate hydrolase, urease, acid phosphatase, and alkaline phosphatase responded positively to elevated CO2 concentrations. Generally, the enzyme activities were highly correlated with each other. Irrespective of the level of CO2, short-term negative influence of chlorpyriphos was observed on soil enzymes till day 7 of spray. Knowledge obtained from this study highlights that the elevated CO2 may negatively influence persistence of pesticide but will have positive effects on soil enzyme activities.

  19. Gemfibrozil and Fenofibrate, Food and Drug Administration-approved Lipid-lowering Drugs, Up-regulate Tripeptidyl-peptidase 1 in Brain Cells via Peroxisome Proliferator-activated Receptor α

    Science.gov (United States)

    Ghosh, Arunava; Corbett, Grant T.; Gonzalez, Frank J.; Pahan, Kalipada

    2012-01-01

    The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an autosomal recessive disease, where the defective gene is Cln2, encoding tripeptidyl-peptidase I (TPP1). At the molecular level, LINCL is caused by accumulation of autofluorescent storage materials in neurons and other cell types. Currently, there is no established treatment for this fatal disease. This study reveals a novel use of gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, in up-regulating TPP1 in brain cells. Both gemfibrozil and fenofibrate up-regulated mRNA, protein, and enzymatic activity of TPP1 in primary mouse neurons and astrocytes as well as human astrocytes and neuronal cells. Because gemfibrozil and fenofibrate are known to activate peroxisome proliferator-activated receptor-α (PPARα), the role of PPARα in gemfibrozil- and fenofibrate-mediated up-regulation of TPP1 was investigated revealing that both drugs up-regulated TPP1 mRNA, protein, and enzymatic activity both in vitro and in vivo in wild type (WT) and PPARβ−/−, but not PPARα−/−, mice. In an attempt to delineate the mechanism of TPP1 up-regulation, it was found that the effects of the fibrate drugs were abrogated in the absence of retinoid X receptor-α (RXRα), a molecule known to form a heterodimer with PPARα. Accordingly, all-trans-retinoic acid, alone or together with gemfibrozil, up-regulated TPP1. Co-immunoprecipitation and ChIP studies revealed the formation of a PPARα/RXRα heterodimer and binding of the heterodimer to an RXR-binding site on the Cln2 promoter. Together, this study demonstrates a unique mechanism for the up-regulation of TPP1 by fibrate drugs via PPARα/RXRα pathway. PMID:22989886

  20. Interaction of the phosphorylated DNA-binding domain in nuclear receptor CAR with its ligand-binding domain regulates CAR activation.

    Science.gov (United States)

    Shizu, Ryota; Min, Jungki; Sobhany, Mack; Pedersen, Lars C; Mutoh, Shingo; Negishi, Masahiko

    2018-01-05

    The nuclear protein constitutive active/androstane receptor (CAR or NR1I3) regulates several liver functions such as drug and energy metabolism and cell growth or death, which are often involved in the development of diseases such as diabetes and hepatocellular carcinoma. CAR undergoes a conversion from inactive homodimers to active heterodimers with retinoid X receptor α (RXRα), and phosphorylation of the DNA-binding domain (DBD) at Thr-38 in CAR regulates this conversion. Here, we uncovered the molecular mechanism by which this phosphorylation regulates the intramolecular interaction between CAR's DBD and ligand-binding domain (LBD), enabling the homodimer-heterodimer conversion. Phosphomimetic substitution of Thr-38 with Asp increased co-immunoprecipitation of the CAR DBD with CAR LBD in Huh-7 cells. Isothermal titration calorimetry assays also revealed that recombinant CAR DBD-T38D, but not nonphosphorylated CAR DBD, bound the CAR LBD peptide. This DBD-LBD interaction masked CAR's dimer interface, preventing CAR homodimer formation. Of note, EGF signaling weakened the interaction of CAR DBD T38D with CAR LBD, converting CAR to the homodimer form. The DBD-T38D-LBD interaction also prevented CAR from forming a heterodimer with RXRα. However, this interaction opened up a CAR surface, allowing interaction with protein phosphatase 2A. Thr-38 dephosphorylation then dissociated the DBD-LBD interaction, allowing CAR heterodimer formation with RXRα. We conclude that the intramolecular interaction of phosphorylated DBD with the LBD enables CAR to adapt a transient monomer configuration that can be converted to either the inactive homodimer or the active heterodimer.

  1. Hydrolysis of ibuprofenoyl-CoA and other 2-APA-CoA esters by human acyl-CoA thioesterases-1 and -2 and their possible role in the chiral inversion of profens.

    Science.gov (United States)

    Qu, Xiao; Allan, Amanda; Chui, Grace; Hutchings, Thomas J; Jiao, Ping; Johnson, Lawrence; Leung, Wai Y; Li, Portia K; Steel, Georgina R; Thompson, Andrew S; Threadgill, Michael D; Woodman, Timothy J; Lloyd, Matthew D

    2013-12-01

    Ibuprofen and related 2-arylpropanoic acid (2-APA) drugs are often given as a racemic mixture and the R-enantiomers undergo activation in vivo by metabolic chiral inversion. The chiral inversion pathway consists of conversion of the drug to the coenzyme A ester (by an acyl-CoA synthetase) followed by chiral inversion by α-methylacyl-CoA racemase (AMACR; P504S). The enzymes responsible for hydrolysis of the product S-2-APA-CoA ester to the active S-2-APA drug have not been identified. In this study, conversion of a variety of 2-APA-CoA esters by human acyl-CoA thioesterase-1 and -2 (ACOT-1 and -2) was investigated. Human recombinant ACOT-1 and -2 (ACOT-1 and -2) were both able to efficiently hydrolyse a variety of 2-APA-CoA substrates. Studies with the model substrates R- and S-2-methylmyristoyl-CoA showed that both enzymes were able to efficiently hydrolyse both of the epimeric substrates with (2R)- and (2S)- methyl groups. ACOT-1 is located in the cytosol and is able to hydrolyse 2-APA-CoA esters exported from the mitochondria and peroxisomes for inhibition of cyclo-oxygenase-1 and -2 in the endoplasmic reticulum. It is a prime candidate to be the enzyme responsible for the pharmacological action of chiral inverted drugs. ACOT-2 activity may be important in 2-APA toxicity effects and for the regulation of mitochondrial free coenzyme A levels. These results support the idea that 2-APA drugs undergo chiral inversion via a common pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Alloying Au surface with Pd reduces the intrinsic activity in catalyzing CO oxidation

    KAUST Repository

    Qian, Kun

    2016-03-30

    © 2016. Various Au-Pd/SiO2 catalysts with a fixed Au loading but different Au:Pd molar ratios were prepared via deposition-precipitation method followed by H2 reduction. The structures were characterized and the catalytic activities in CO oxidation were evaluated. The formation of Au-Pd alloy particles was identified. The Au-Pd alloy particles exhibit enhanced dispersions on SiO2 than Au particles. Charge transfer from Pd to Au within Au-Pd alloy particles. Isolated Pd atoms dominate the surface of Au-Pd alloy particles with large Au:Pd molar ratios while contiguous Pd atoms dominate the surface of Au-Pd alloy particles with small Au:Pd molar ratios. Few synergetic effect of Au-Pd alloy occurs on catalyzing CO oxidation under employed reaction conditions. Alloying Au with Pd reduces the intrinsic activity in catalyzing CO oxidation, and contiguous Pd atoms on the Au-Pd alloy particles are capable of catalyzing CO oxidation while isolated Pd atoms are not. These results advance the fundamental understandings of Au-Pd alloy surfaces in catalyzing CO oxidation.

  3. Mycotoxins: Risks, regulations and European co-operation

    Directory of Open Access Journals (Sweden)

    Van Egmond Hans P.

    2013-01-01

    Full Text Available Mycotoxins and mycotoxicises have been problems of the past and the present, but scientific attention for mycotoxins did not start until the early 1960’s. Nowa­days, many mycotoxins are known, and their occurrence in food and animal feed may cause various adverse effects on human and animal health, including carcinogenic, hepatotoxic, immunotoxic, nephrotoxic, neurotoxic, oestrogenic and teratogenic effects. Some important mycotoxins include the aflatoxins, ochratoxin A, the fumonisins and the trichothecenes, and their significance is briefly described. To protect human and animal health, many countries have enacted specific regulations for mycotoxins in food and animal feed. Risk assessment is a major factor for scientific underpinning of regulations, but other factors such as availability of adequate sampling and analysis procedures also play an important a role in the establishment of mycotoxin regulations. In addition, socio-economic factors such as cost-benefit considerations, trade issues and sufficiency of food supply are equally important in the decision-taking process to come to meaningful regulations. Nowadays, more than 100 countries have formal mycotoxin regulations for food and feed. The mycotoxin regulations are the most stringent in the EU, where various organizations and pan-European networks contribute to combat the mycotoxin problem. It is to be expected that mycotoxins will stay with us in the future and climate change might have a negative influence in this respect. Several possibilities exist to mitigate the problems caused by mycotoxins. In particular prevention of mould growth and mycotoxin formation is key to the control of mycotoxins.

  4. PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

    DEFF Research Database (Denmark)

    Chung, Ho-Ryun; Xu, Chao; Fuchs, Alisa

    2016-01-01

    and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA Pol......II. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue...... that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes....

  5. Reciprocal regulation of LXRα activity by ASXL1 and ASXL2 in lipogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ui-Hyun; Seong, Mi-ran [Department of Bioscience and Biotechnology, Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747 (Korea, Republic of); Kim, Eun-Joo; Hur, Wonhee; Kim, Sung Woo [Department of Molecular Biology, BK21 Graduate Program, Dankook University, Gyeonggi-do 448-701 (Korea, Republic of); Yoon, Seung Kew [The Catholic University Liver Research Center and WHO Collaborating Center of Viral Hepatitis, The Catholic University, College of Medicine, Seoul 137-701 (Korea, Republic of); Um, Soo-Jong, E-mail: umsj@sejong.ac.kr [Department of Bioscience and Biotechnology, Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747 (Korea, Republic of)

    2014-01-10

    Highlights: •ASXL1 and ASXL2 directly interact with ligand-bound LXRα. •Ligand-induced LXRα activity is repressed by ASXL1 and activated by ASXL2. •ASXL1 and ASXL2 bind to the LXRE of the LXRα target promoter. •ASXL1 and ASXL2 reciprocally regulate lipogenesis in liver cells. -- Abstract: Liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, plays a pivotal role in hepatic cholesterol and lipid metabolism, regulating the expression of genes associated with hepatic lipogenesis. The additional sex comb-like (ASXL) family was postulated to regulate chromatin function. Here, we investigate the roles of ASXL1 and ASXL2 in regulating LXRα activity. We found that ASXL1 suppressed ligand-induced LXRα transcriptional activity, whereas ASXL2 increased LXRα activity through direct interaction in the presence of the ligand. Chromatin immunoprecipitation (ChIP) assays showed ligand-dependent recruitment of ASXLs to ABCA1 promoters, like LXRα. Knockdown studies indicated that ASXL1 inhibits, while ASXL2 increases, lipid accumulation in H4IIE cells, similar to their roles in transcriptional regulation. We also found that ASXL1 expression increases under fasting conditions, and decreases in insulin-treated H4IIE cells and the livers of high-fat diet-fed mice. Overall, these results support the reciprocal role of the ASXL family in lipid homeostasis through the opposite regulation of LXRα.

  6. Effect of Activation Temperature on CO{sub 2} Capture Behaviors of Resorcinol-based Carbon Aerogels

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Cheolwhan; Im, Seungsoon; Park, Soojin [Hanyang Univ., Seoul (Korea, Republic of); Kim, Youngjoo [Inha Univ., Incheon (Korea, Republic of)

    2014-01-15

    In this study, carbon aerogel (CA) was synthesized using a soft-template method, and the optimum conditions for the adsorption of carbon dioxide (CO{sub 2}) by the carbon aerogel were evaluated by controlling the activation temperature. KOH was used as the activation agent at a KOH/CA activation ratio of 4:1. Three types of activated CAs were synthesized at activation temperatures of 800 .deg. C (CA-K-800), 900 .deg. C (CA-K-900), and 1000 .deg. C (CA-K-1000), and their surface and pore characteristics along with the CO{sub 2} adsorption characteristics were examined. The results showed that with the increase in activation temperature from 800 to 900 .deg. C, the total pore volume and specific surface area sharply increased from 1.2165 to 1.2500 cm{sup 3}/g and 1281 to 1526 m{sup 2}/g, respectively. However, the values for both these parameters decreased at temperatures above 1000 .deg. C. The best CO{sub 2} adsorption capacity of 10.9 wt % was obtained for the CA-K-900 sample at 298 K and 1 bar. This result highlights the importance of the structural and textural characteristics of the carbon aerogel, prepared at different activation temperatures on CO{sub 2} adsorption behaviors.

  7. How to develop students’ approaches to learning: Experiences from a programme based on co-regulated learning

    Directory of Open Access Journals (Sweden)

    Stančić Milan

    2017-01-01

    Full Text Available Starting from the insight that during their education students do not manage to learn how to learn, we created the programme called Blooming with the intention of enabling the students to reconsider their own approaches to learning by developing collaborative activities and relations in the classroom. The programme was realised in a secondary school class, and research goals were to explore the contribution of the programme to the change in students’ approach to learning - regarding the learning motivation and strategies - and to obtain an insight into students’ perspective of the benefits of the programme. The changes in learning strategies and students’ motivation were investigated using the MSLQ before and after programme attendance. The data on the programme benefits were obtained via focus groups with students and analysed by the thematic content analysis. It has been established that the students achieved a significant improvement when it comes to the mastering of the learning strategies that refer to self-regulation, critical thinking, peer learning and help seeking. In addition, the students pointed out as benefits a different method of work and pleasant atmosphere, the feeling of autonomy in classes, as well as the development of a different understanding of the nature of knowledge, the learning process and instruction. The results indicate that the use of Bloom’s taxonomy as the tool for co-regulated learning and self-evaluation of students can contribute to the change in students’ learning approaches. This finding is relevant for further considering of the possibility for this method to grow from a special programme into everyday teaching practice.

  8. DMPD: Genetic regulation of macrophage priming/activation: the Lsh gene story. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1757110 Genetic regulation of macrophage priming/activation: the Lsh gene story. Bl... (.svg) (.html) (.csml) Show Genetic regulation of macrophage priming/activation: the Lsh gene story. Pubmed...ID 1757110 Title Genetic regulation of macrophage priming/activation: the Lsh gen

  9. Effect of Relative Humidity on Adsorption Breakthrough of CO2 on Activated Carbon Fibers

    Directory of Open Access Journals (Sweden)

    Yu-Chun Chiang

    2017-11-01

    Full Text Available Microporous activated carbon fibers (ACFs were developed for CO2 capture based on potassium hydroxide (KOH activation and tetraethylenepentamine (TEPA amination. The material properties of the modified ACFs were characterized using several techniques. The adsorption breakthrough curves of CO2 were measured and the effect of relative humidity in the carrier gas was determined. The KOH activation at high temperature generated additional pore networks and the intercalation of metallic K into the carbon matrix, leading to the production of mesopore and micropore volumes and providing access to the active sites in the micropores. However, this treatment also resulted in the loss of nitrogen functionalities. The TEPA amination has successfully introduced nitrogen functionalities onto the fiber surface, but its long-chain structure blocked parts of the micropores and, thus, made the available surface area and pore volume limited. Introduction of the power of time into the Wheeler equation was required to fit the data well. The relative humidity within the studied range had almost no effects on the breakthrough curves. It was expected that the concentration of CO2 was high enough so that the impact on CO2 adsorption capacity lessened due to increased relative humidity.

  10. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  11. USP21 regulates Hippo pathway activity by mediating MARK protein turnover

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Loya, Anand Chainsukh

    2017-01-01

    observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components...

  12. The Cloning and Functional Characterization of Peach CONSTANS and FLOWERING LOCUS T Homologous Genes PpCO and PpFT.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    Full Text Available Flowering is an essential stage of plant growth and development. The successful transition to flowering not only ensures the completion of plant life cycles, it also serves as the basis for the production of economically important seeds and fruits. CONSTANS (CO and FLOWERING LOCUS T (FT are two genes playing critical roles in flowering time control in Arabidopsis. Through homology-based cloning and rapid-amplifications of cDNA ends (RACE, we obtained full-lengths cDNA sequences of Prunus persica CO (PpCO and Prunus persica FT (PpFT from peach (Prunus persica (L. Batsch and investigated their functions in flowering time regulation. PpCO and PpFT showed high homologies to Arabidopsis CO and FT at DNA, mRNA and protein levels. We showed that PpCO and PpFT were nucleus-localized and both showed transcriptional activation activities in yeast cells, consistent with their potential roles as transcription activators. Moreover, we established that the over-expression of PpCO could restore the late flowering phenotype of the Arabidopsis co-2 mutant, and the late flowering defect of the Arabidopsis ft-1 mutant can be rescued by the over-expression of PpFT, suggesting functional conservations of CO and FT genes in peach and Arabidopsis. Our results suggest that PpCO and PpFT are homologous genes of CO and FT in peach and they may function in regulating plant flowering time.

  13. Comparative study of CO2 and H2O activation in the synthesis of carbon electrode for supercapacitors

    Science.gov (United States)

    Taer, E.; Apriwandi, Yusriwandi, Mustika, W. S.; Zulkifli, Taslim, R.; Sugianto, Kurniasih, B.; Agustino, Dewi, P.

    2018-02-01

    The physical activation for the comparative study of carbon electrode synthesized for supercapacitor applications made from rubber wood sawdust has been performed successfully. Comparison of physical activation used in this research is based on the different gas activation such as CO2 and H2O. The CO2 and H2O activation are made by using an integrated carbonization and activation system. The carbonization process is performed in N2 atmosphere followed by CO2 and H2O activation process. The carbonization process at temperature of 600°C, the CO2 and H2O activation process at a temperature of 900°C and maintained at this condition for 2 h and 3 h. The electrochemical properties were analyzed using cyclic voltammetric (CV) method. The CV results show that the carbon electrode with CO2 activation has better capacitive properties than H2O, the highest specific capacitance obtained is 93.22 F/g for 3 h of activation time. In addition, the analysis of physical properties such as surface morphology and degree of crystallinity was also performed.

  14. Bi-directional astrocytic regulation of neuronal activity within a network

    Directory of Open Access Journals (Sweden)

    Susan Yu Gordleeva

    2012-11-01

    Full Text Available The concept of a tripartite synapse holds that astrocytes can affect both the pre- and postsynaptic compartments through the Ca2+-dependent release of gliotransmitters. Because astrocytic Ca2+ transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the postsynaptic currents. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

  15. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation

    DEFF Research Database (Denmark)

    Dzamko, Nicolas; Schertzer, Jonathan D.; Ryall, James G.

    2008-01-01

    The activation of AMP-activated protein kinase (AMPK) and phosphorylation/inhibition of acetyl-CoA carboxylase 2 (ACC2) is believed to be the principal pathway regulating fatty acid oxidation. However, during exercise AMPK activity and ACC Ser-221 phosphorylation does not always correlate...... with rates of fatty acid oxidation. To address this issue we have investigated the requirement for skeletal muscle AMPK in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) and contraction-stimulated fatty acid oxidation utilizing transgenic mice expressing a muscle-specific kinase...... dead (KD) AMPK alpha2. In wild-type (WT) mice, AICAR and contraction increased AMPK alpha2 and alpha1 activities, the phosphorylation of ACC2 and rates of fatty acid oxidation while tending to reduce malonyl-CoA levels. Despite no activation of AMPK in KD mic