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  1. Connexin 32 and connexin 43 are involved in lineage restriction of hepatic progenitor cells to hepatocytes

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    Haiyun Pei

    2017-11-01

    Full Text Available Abstract Background Bi-potential hepatic progenitor cells can give rise to both hepatocytes and cholangiocytes, which is the last phase and critical juncture in terms of sequentially hepatic lineage restriction from any kind of stem cells. If their differentiation can be controlled, it might access to functional hepatocytes to develop pharmaceutical and biotechnology industries as well as cell therapies for end-stage liver diseases. Methods In this study, we investigated the influence of Cx32 and Cx43 on hepatocyte differentiation of WB-F344 cells by in vitro gain and loss of function analyses. An inhibitor of Cx32 was also used to make further clarification. To reveal p38 MAPK pathway is closely related to Cxs, rats with 70% partial hepatectomy were injected intraperitoneally with a p38 inhibitor, SB203580. Besides, the effects of p38 MAPK pathway on differentiation of hepatoblasts isolated from fetal rat livers were evaluated by addition of SB203580 in culture medium. Results In vitro gain and loss of function analyses showed overexpression of Connexin 32 and knockdown of Connexin 43 promoted hepatocytes differentiation from hepatic progenitor cells. In addition, in vitro and ex vivo research revealed inhibition of p38 mitogen-activated protein kinase pathway can improve hepatocytes differentiation correlating with upregulation of Connexin 32 expression and downregulation of Connexin 43 expression. Conclusions Here we demonstrate that Connexins play crucial roles in facilitating differentiation of hepatic progenitors. Our work further implicates that regulators of Connexins and their related pathways might provide new insights to improve lineage restriction of stem cells to mature hepatocytes.

  2. Connexin43 orthologues in vertebrates: phylogeny from fish to man

    NARCIS (Netherlands)

    van der Heyden, Marcel A. G.; van Eijk, Marleen; Wilders, Ronald; de Bakker, Jacques M. T.; Opthof, Tobias

    2004-01-01

    The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization

  3. Connexin43 gene and its irradiation-induced expression

    International Nuclear Information System (INIS)

    Long Xianhui; Zhou Pingkun

    2005-01-01

    Gap junctions, composed of connexin protein subunits, provide the important channel for the intercellular communication. Connexin43, the most popular component of the connexin protein family, is widely expressed in multiple tissues and cell lines and plays an important role in cell proliferation, differention and tissue homeostasis. Recently it was reported that the expression of connexin43 gene is remarkedly up-regulated by low dose ionizing radiation, the available data suggest connexin43 gene to be a poten-tial sensitive bio-marker in radiation damage. (authors)

  4. Regulation of connexin26 and connexin43 expression in rat endometrium by ovarian steroid hormones.

    Science.gov (United States)

    Grümmer, R; Chwalisz, K; Mulholland, J; Traub, O; Winterhager, E

    1994-12-01

    A distinct spatial and temporal pattern of connexin26 and connexin43 (cx26 and cx43) expression was observed in the rat endometrium in response to embryo implantation; however, connexin expression was suppressed during the preimplantation period. Pseudopregnant rats did not show connexin mRNA, while artificial decidualization induced by a scratch led to a strong expression of cx26 and cx43 in the endometrium of these animals. In order to examine the regulatory effects of ovarian steroid hormones on connexin expression, ovariectomized rats were treated with progesterone (P) and/or estradiol-17 beta (E2). Untreated, ovariectomized animals expressed mRNA for cx43, but not for cx26. Endometrial expression of mRNA for both connexins was strongly enhanced by E2 treatment; immunolabeling revealed protein for cx26 in the uterine luminal epithelial cells and for cx43 in the uterine stromal cells. P treatment, either alone or in combination with E2, suppressed expression of connexin mRNA. P suppression in the presence of E2 was reversible when P was withdrawn. When administered on Days 0-2 of pregnancy, the antiprogestin onapristone inhibited the effect of P and gave rise to strong expression of both connexin transcripts. These results demonstrate that expression of cx26 and cx43 in the rat uterine endometrium is differentially regulated by E2 and P during early pregnancy.

  5. Gap junction protein connexin-43 interacts directly with microtubules

    NARCIS (Netherlands)

    Giepmans, B N; Verlaan, I; Hengeveld, T; Janssen, H; Calafat, J; Falk, M M; Moolenaar, W H

    2001-01-01

    Gap junctions are specialized cell-cell junctions that mediate intercellular communication. They are composed of connexin proteins, which form transmembrane channels for small molecules [1, 2]. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated

  6. Gap junction protein connexin43 exacerbates lung vascular permeability.

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    James J O'Donnell

    Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

  7. Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin

    NARCIS (Netherlands)

    Giepmans, B N; Verlaan, I; Moolenaar, W H

    2001-01-01

    Gap junctions are composed of connexins that form transmembrane channels between adjacent cells. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated in the regulation of Cx43 channel gating. Interestingly, channel-independent processes regulated

  8. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

    Science.gov (United States)

    Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-01-01

    Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

  9. Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

    International Nuclear Information System (INIS)

    Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

    2010-01-01

    Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

  10. Targeting connexin 43 in diabetic wound healing: Future perspectives

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    Bajpai S

    2009-01-01

    Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

  11. Green fluorescent protein changes the conductance of connexin 43 (Cx43) hemichannels reconstituted in planar lipid bilayers.

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    Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

    2012-01-20

    In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein.

  12. Association of connexin43 with a receptor protein tyrosine phosphatase

    NARCIS (Netherlands)

    Giepmans, Ben N G; Feiken, Elles; Gebbink, Martijn F B G; Moolenaar, Wouter H

    2003-01-01

    Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap

  13. Green Fluorescent Protein Changes the Conductance of Connexin 43 (Cx43) Hemichannels Reconstituted in Planar Lipid Bilayers*

    Science.gov (United States)

    Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

    2012-01-01

    In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein. PMID:22139870

  14. Friend or foe: Endoplasmic reticulum protein 29 (ERp29) in epithelial cancer

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    Chen, Shaohua; Zhang, Daohai

    2015-01-01

    The endoplasmic reticulum (ER) protein 29 (ERp29) is a molecular chaperone that plays a critical role in protein secretion from the ER in eukaryotic cells. Recent studies have also shown that ERp29 plays a role in cancer. It has been demonstrated that ERp29 is inversely associated with primary tumor development and functions as a tumor suppressor by inducing cell growth arrest in breast cancer. However, ERp29 has also been reported to promote epithelial cell morphogenesis, cell survival against genotoxic stress and distant metastasis. In this review, we summarize the current understanding on the biological and pathological functions of ERp29 in cancer and discuss the pivotal aspects of ERp29 as “friend or foe” in epithelial cancer. PMID:25709888

  15. Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

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    Malmström Anders

    2006-05-01

    Full Text Available Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7, term pregnant women not in labour (n = 14, in normal labour (n = 7 and in prolonged labour (n = 7. mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

  16. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

    NARCIS (Netherlands)

    van Zeijl, Leonie; Ponsioen, Bas; Giepmans, Ben N G; Ariaens, Aafke; Postma, Friso R; Várnai, Péter; Balla, Tamas; Divecha, Nullin; Jalink, Kees; Moolenaar, Wouter H

    2007-01-01

    Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol

  17. The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein

    NARCIS (Netherlands)

    Giepmans, B N; Moolenaar, W H

    1998-01-01

    Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins, termed connexins [1-3]. Connexin43 (Cx43) is the most widely expressed and the most well-studied member of this family. Cx43-based cell-cell communication is regulated

  18. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

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    Guoqiang Zhong

    2017-05-01

    Full Text Available In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2 is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge of the crossing molecules.

  19. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

    Science.gov (United States)

    Zhong, Guoqiang; Akoum, Nazem; Appadurai, Daniel A.; Hayrapetyan, Volodya; Ahmed, Osman; Martinez, Agustin D.; Beyer, Eric C.; Moreno, Alonso P.

    2017-01-01

    In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2) is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj) for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge) of the crossing molecules. PMID:28611680

  20. The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

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    Mélanie Busby

    2018-02-01

    Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

  1. The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

    Science.gov (United States)

    Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

    2018-01-01

    Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

  2. Expression of connexin 37, 40 and 43 in rat mesenteric arterioles and resistance arteries

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Mikkelsen, Hanne B; Arensbak, Birgitte

    2003-01-01

    Connexins are the protein constituents of gap junctions which mediate intercellular communication in most tissues. In arterioles gap junctions appear to be important for conduction of vasomotor responses along the vessel. Studies of the expression pattern of connexin isoforms in the microcirculat......Connexins are the protein constituents of gap junctions which mediate intercellular communication in most tissues. In arterioles gap junctions appear to be important for conduction of vasomotor responses along the vessel. Studies of the expression pattern of connexin isoforms...... in the microcirculation are sparse. We investigated the expression of the three major vascular connexins in mesenteric arterioles (diameter micro m) from male Sprague-Dawley rats, since conducted vasomotor responses have been described in these vessels. The findings were compared with those obtained from upstream...... small resistance arteries. Indirect immunofluorescence techniques were used on whole mounts of mesenteric arterioles and on frozen sections of resistance arteries (diameter approximately 300 micro m). Mesenteric arterioles expressed Cx40 and Cx43 in the endothelial layer, and Cx37 was found in most...

  3. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring.

    Science.gov (United States)

    Rossini, Kamila Fernanda; Oliveira, Camila Andrea de; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-07-01

    The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. A limitação dietética durante a gravidez influencia o crescimento e desenvolvimento do feto e da prole e sua saúde na vida adulta. Os mecanismos subjacentes dos efeitos adversos da restrição proteica gestacional (RPG) no desenvolvimento dos corações da prole não são bem compreendidos. Avaliar os efeitos da RPG sobre a estrutura cardíaca em filhotes machos de ratas aos 60 dias após o nascimento (d60). Ratos fêmeas Wistar grávidas foram alimentadas com uma dieta de proteína normal (PN, 17% caseína) ou de baixa proteína (BP, caseína 6%). Os valores de pressão arterial (PA) de descendentes do sexo masculino de

  4. Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

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    Hossein Mostafavi

    2014-02-01

    Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

  5. c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

    International Nuclear Information System (INIS)

    Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang

    2007-01-01

    AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

  6. Studies on level of cytokines and expression of connexin43 in tumor and normal cells in culture conditions

    International Nuclear Information System (INIS)

    Asati, V.; Pandey, B.N.

    2016-01-01

    Factors secreted from the tumor cells in culture medium have been known to facilitate the growth of fresh cultures and also to affect the cellular radio-sensitivity. Moreover, expression of gap junction proteins like connexin-43 is known as a key player in cell survival and proliferation. The present study is aimed to evaluate the effects of conditioned medium on the growth of respective tumor/normal cells and the expression of connexin-43 in these cells

  7. Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory

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    Laura Walrave

    2016-12-01

    Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

  8. TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

    Science.gov (United States)

    Li, Hanjun; Spagnol, Gaelle; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

    2014-01-01

    ABSTRACT Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperature-sensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phospho-specific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health. PMID:24849651

  9. Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias

    NARCIS (Netherlands)

    Fernandes, Sarah; van Rijen, Harold V. M.; Forest, Virginie; Evain, Stéphane; Leblond, Anne-Laure; Mérot, Jean; Charpentier, Flavien; de Bakker, Jacques M. T.; Lemarchand, Patricia

    2009-01-01

    Cell-based therapies have great potential for the treatment of cardiovascular diseases. Recently, using a transgenic mouse model Roell et al. reported that cardiac engraftment of connexin43 (Cx43)-overexpressing myoblasts in vivo prevents post-infarct arrhythmia, a common cause of death in patients

  10. Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

    Directory of Open Access Journals (Sweden)

    Miaki Uzu

    2015-05-01

    Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

  11. Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels

    DEFF Research Database (Denmark)

    Alstrøm, Jette Skov; Stroemlund, Line Waring; Nielsen, Morten Schak

    2015-01-01

    Connexin43 (Cx43) generates intercellular gap junction channels involved in, among others, cardiac and brain function. Gap junctions are formed by the docking of two hemichannels from neighbouring cells. Undocked Cx43 hemichannels can upon different stimuli open towards the extracellular matrix...... and allow transport of molecules such as fluorescent dyes and ATP. A range of phosphorylated amino acids have been detected in the C-terminus of Cx43 and their physiological role has been intensively studied both in the gap junctional form of Cx43 and in its hemichannel configuration. We present the current...... knowledge of protein kinase C (PKC)-dependent regulation of Cx43 and discuss the divergent results....

  12. The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

    Science.gov (United States)

    Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  13. Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.

    Science.gov (United States)

    Grippo, Angela J; Moffitt, Julia A; Henry, Matthew K; Firkins, Rachel; Senkler, Jonathan; McNeal, Neal; Wardwell, Joshua; Scotti, Melissa-Ann L; Dotson, Ashley; Schultz, Rachel

    2015-01-01

    Exposure to social and environmental stressors may influence behavior as well as autonomic and cardiovascular regulation, potentially leading to depressive disorders and cardiac dysfunction including elevated sympathetic drive, reduced parasympathetic function, and ventricular arrhythmias. The cellular mechanisms that underlie these interactions are not well understood. One mechanism may involve alterations in the expression of Connexin43 (Cx43) and Connexin45 (Cx45), gap junction proteins in the heart that play an important role in ensuring efficient cell-to-cell coupling and the maintenance of cardiac rhythmicity. The present study investigated the hypothesis that long-term social isolation, combined with mild environmental stressors, would produce both depressive behaviors and altered Cx43 and Cx45 expression in the left ventricle of prairie voles - a socially monogamous rodent model. Adult, female prairie voles were exposed to either social isolation (n = 22) or control (paired, n = 23) conditions (4 weeks), alone or in combination with chronic mild stress (CMS) (1 week). Social isolation, versus paired control conditions, produced significantly (p Social isolation (alone) reduced (p social and environmental stress in the prairie vole.

  14. Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

    Directory of Open Access Journals (Sweden)

    Mauricio A. Retamal

    2017-11-01

    Full Text Available In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia. It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs. Recent evidence shows that connexin43 (Cx43 hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

  15. Sex differences in connexin-43 expression in left ventricles of aging rats

    Czech Academy of Sciences Publication Activity Database

    Tribulová, N.; Dupont, E.; Soukup, Tomáš; Okruhlicová, L.; Severs, N. J.

    2005-01-01

    Roč. 54, č. 6 (2005), s. 705-708 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/05/0327 Grant - others:MYORES(XE) 511978; CZ-SK(CZ) 02-2004-05 Institutional research plan: CEZ:AV0Z50110509 Keywords : connexin-43 * rat cardiomyocytes * male and female specificity Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

  16. Effect of Beta-Carotene on Oxidative Stress and Expression of Cardiac Connexin 43

    Energy Technology Data Exchange (ETDEWEB)

    Novo, Rosangela; Azevedo, Paula S.; Minicucci, Marcos F.; Zornoff, Leonardo A. M., E-mail: lzornoff@fmb.unesp.br; Paiva, Sergio A. R. [Faculdade de Medicina de Botucatu - Universidade Estadual Paulista ' Júlio de Mesquita Filho' , Botucatu, SP (Brazil)

    2013-09-15

    Intervention studies have shown an increased mortality in patients who received beta-carotene. However, the mechanisms involved in this phenomenon are still unknown. Evaluate the influence of beta-carotene on oxidative stress and the expression of connexin 43 in rat hearts. Wistar rats, weighing approximately 100 g, were allocated in two groups: Control Group (n = 30), that received the diet routinely used in our laboratory, and Beta-Carotene Group (n = 28), which received beta-carotene (in crystal form, added and mixed to the diet) at a dose of 500 mg of beta carotene/kg of diet. The animals received the treatment until they reached 200-250g, when they were sacrificed. Samples of blood, liver and heart were collected to perform Western blotting and immunohistochemistry for connexin 43; morphometric studies, dosages of beta carotene by high performance liquid chromatography as well as reduced glutathione, oxidized glutathione and lipids hydroperoxides were performed by biochemical analysis. Beta-carotene was detected only in the liver of Beta-Carotene Group animals (288 ± 94.7 μg/kg). Levels of reduced/ oxidized glutathione were higher in the liver and heart of Beta-Carotene Group animals (liver - Control Group: 42.60 ± 1.62; liver - Beta-Carotene Group: 57.40 ± 5.90; p = 0.04; heart: - Control Group: 117.40 ± 1.01; heart - Beta-Carotene Group: 121.81 ± 1.32 nmol/mg protein; p = 0.03). The content of total connexin 43 was larger in Beta-Carotene Group. Beta-carotene demonstrated a positive effect, characterized by the increase of intercellular communication and improvement of anti-oxidizing defense system. In this model, mechanism does not explain the increased mortality rate observed with the beta-carotene supplementation in clinical studies.

  17. Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Shuo Liu

    Full Text Available Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases

  18. Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

    Science.gov (United States)

    Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

    2015-01-01

    Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

  19. Astrocyte and Oligodendrocyte Connexins of the Glial Syncytium in Relation to Astrocyte Anatomical Domains and Spatial Buffering

    OpenAIRE

    NAGY, JAMES I.; RASH, JOHN E.

    2003-01-01

    Astroctyes express a set of three connexins (Cx26, Cx30, and Cx43) that are contained in astrocyte-to-astrocyte (A/A) gap junctions; oligodendrocytes express a different set of three connexins (Cx29, Cx32, and Cx47) that are contained in the oligodendrocyte side of necessarily heterotypic astrocyte-to-oligodendrocyte (A/O) gap junctions, and there is little ultrastructural evidence for gap junction formation between individual oligodendrocytes. In addition, primarily Cx29 and Cx32 are contain...

  20. Down-regulation of Connexin43 expression reveals the involvement of caveolin-1 containing lipid rafts in human U251 glioblastoma cell invasion.

    Science.gov (United States)

    Strale, Pierre-Olivier; Clarhaut, Jonathan; Lamiche, Coralie; Cronier, Laurent; Mesnil, Marc; Defamie, Norah

    2012-11-01

    Glioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap-junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down-regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that the invasion capacity measured in vitro and ex vivo correlates with Cx43 expression level. For the first time in a cancer cell context, our work demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with a lipid raft marker, caveolin-1 and that this interaction is inversely correlated to the level of Cx43. This localization of Cx43 in these lipid raft microdomains regulates both homo- and heterocellular gap junctional communications (respectively between U251 cells, or between U251 cells and astrocytes). Moreover, the adhesive and invasive capacities are not dependent, in our model, on Cav-1 expression level. Our results tend to show that heterocellular gap junctional communication between cancer and stroma cells may affect the behavior of the tumor cells. Altogether, our data demonstrate that Cx43 controls the tumor phenotype of glioblastoma U251 cells and in particular, invasion capacity, through its localization in lipid rafts containing Cav-1. Copyright © 2011 Wiley Periodicals, Inc.

  1. Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication

    Science.gov (United States)

    Garciarena, Carolina D.; Malik, Akif; Swietach, Pawel; Moreno, Alonso P.; Vaughan-Jones, Richard D.

    2018-01-01

    Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional channels. To regulate signal transmission, connexin (Cx) channel permeability must respond dynamically to physiological and pathophysiological stimuli. One key stimulus is intracellular pH (pHi), which is modulated by a tissue’s metabolic and perfusion status. Our understanding of the molecular mechanism of H+ gating of Cx43 channels—the major isoform in the heart and brain—is incomplete. To interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging, performed over a range of pHi values. We demonstrate that Cx43 channels expressed in HeLa or N2a cell pairs are gated biphasically by pHi via a process that consists of activation by H+ ions at alkaline pHi and inhibition at more acidic pHi. For Cx43 channel–mediated solute/ion transmission, the ensemble of these effects produces a pHi optimum, near resting pHi. By using Cx43 mutants, we demonstrate that alkaline gating involves cysteine residues of the C terminus and is independent of motifs previously implicated in acidic gating. Thus, we present a molecular mechanism by which cytoplasmic acid–base chemistry fine tunes intercellular communication and establishes conditions for the optimal transmission of solutes and signals in tissues, such as the heart and brain.—Garciarena, C. D., Malik, A., Swietach, P., Moreno, A. P., Vaughan-Jones, R. D. Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication. PMID:29183963

  2. Different domains are critical for oligomerization compatibility of different connexins

    Science.gov (United States)

    MARTÍNEZ, Agustín D.; MARIPILLÁN, Jaime; ACUÑA, Rodrigo; MINOGUE, Peter J.; BERTHOUD, Viviana M.; BEYER, Eric C.

    2011-01-01

    Oligomerization of connexins is a critical step in gap junction channel formation. Some members of the connexin family can oligomerize with other members and form functional heteromeric hemichannels [e.g. Cx43 (connexin 43) and Cx45], but others are incompatible (e.g. Cx43 and Cx26). To find connexin domains important for oligomerization, we constructed chimaeras between Cx43 and Cx26 and studied their ability to oligomerize with wild-type Cx43, Cx45 or Cx26. HeLa cells co-expressing Cx43, Cx45 or Cx26 and individual chimaeric constructs were analysed for interactions between the chimaeras and the wild-type connexins using cell biological (subcellular localization by immunofluorescence), functional (intercellular diffusion of microinjected Lucifer yellow) and biochemical (sedimentation velocity through sucrose gradients) assays. All of the chimaeras containing the third transmembrane domain of Cx43 interacted with wild-type Cx43 on the basis of co-localization, dominant-negative inhibition of intercellular communication, and altered sedimentation velocity. The same chimaeras also interacted with co-expressed Cx45. In contrast, immunofluorescence and intracellular diffusion of tracer suggested that other domains influenced oligomerization compatibility when chimaeras were co-expressed with Cx26. Taken together, these results suggest that amino acids in the third transmembrane domain are critical for oligomerization with Cx43 and Cx45. However, motifs in different domains may determine oligomerization compatibility in members of different connexin subfamilies. PMID:21348854

  3. Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

  4. Differential Connexin Function Enhances Self-Renewal in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Masahiro Hitomi

    2015-05-01

    Full Text Available The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43, but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.

  5. Multifaceted Roles of Connexin 43 in Stem Cell Niches.

    Science.gov (United States)

    Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

    2018-01-01

    Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

  6. Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43

    NARCIS (Netherlands)

    Boogerd, Kees-Jan; Wong, L. Y. Elaine; Christoffels, Vincent M.; Klarenbeek, Meinke; Ruijter, Jan M.; Moorman, Antoon F. M.; Barnett, Phil

    2008-01-01

    AIMS: T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering

  7. The B[a]P-increased intercellular communication via translocation of connexin-43 into gap junctions reduces apoptosis

    International Nuclear Information System (INIS)

    Tekpli, X.; Rivedal, E.; Gorria, M.; Landvik, N.E.; Rissel, M.; Dimanche-Boitrel, M.-T.; Baffet, G.; Holme, J.A.; Lagadic-Gossmann, D.

    2010-01-01

    Gap junctions are channels in plasma membrane composed of proteins called connexins. These channels are organized in special domains between cells, and provide for direct gap junctional intercellular communication (GJIC), allowing diffusion of signalling molecules < 1 kD. GJIC regulates cell homeostasis and notably the balance between proliferation, cell cycle arrest, cell survival and apoptosis. Here, we have investigated benzo[a]pyrene (B[a]P) effects on GJIC and on the subcellular localization of the major protein of gap junction: connexin-43 (Cx43). Our results showed that B[a]P increased GJIC between mouse hepatoma Hepa1c1c7 cells via translocation of Cx43 from Golgi apparatus and lipid rafts into gap junction plaques. Interestingly, inhibition of GJIC by chlordane or small interference RNA directed against Cx43 enhanced B[a]P-induced apoptosis in Hepa1c1c7 cells. The increased apoptosis caused by inhibition of GJIC appeared to be mediated by ERK/MAPK pathway. It is suggested that B[a]P could induce transfer of cell survival signal or dilute cell death signal via regulation of ERK/MAPK through GJIC.

  8. Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

    Energy Technology Data Exchange (ETDEWEB)

    Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States); Panda, Satya P., E-mail: panda@uthscsa.edu [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States)

    2011-08-05

    Highlights: {yields} Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. {yields} First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. {yields} Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. {yields} Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. {yields} Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b{sub 5} and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

  9. Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

    International Nuclear Information System (INIS)

    Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue; Panda, Satya P.

    2011-01-01

    Highlights: → Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. → First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. → Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. → Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. → Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b 5 and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

  10. The oligodendroglial precursor cell line Oli-neu represents a cell culture system to examine functional expression of the mouse gap junction gene connexin29 (Cx29

    Directory of Open Access Journals (Sweden)

    Goran Christoph Söhl

    2013-06-01

    Full Text Available The potential gap junction forming mouse connexin29 (Cx29 protein is concomitantly expressed with connexin32 (Cx32 in peripheral myelin forming Schwann cells and together with both Cx32 and connexin47 (Cx47 in oligodendrocytes of the CNS. To study the genomic structure and functional expression of Cx29, either primary cells or cell culture systems might be selected, from which the latter are easier to cultivate. Both structure and expression of Cx29 is still not fully understood. In the mouse sciatic nerve, brain and the oligodendroglial precursor cell line Oli-neu the Cx29 gene is processed in two transcript isoforms both harbouring a unique reading frame. In contrast to Cx32 and Cx47, only Cx29 protein is abundantly expressed in undifferentiated as well as differentiated Oli-neu cells but the absence of Etbr dye transfer after microinjection concealed the function of Cx29 mediated gap junction communication between those cells. Although HeLa cells stably transfected with Cx29 or Cx29-eGFP neither demonstrated any permeability for Lucifer yellow nor for neurobiotin, blocking of Etbr uptake from the media by gap junction blockers does suppose a role of Cx29 in hemi-channel function. Thus, we conclude that, due to its high abundance of Cx29 expression and its reproducible culture conditions, the oligodendroglial precursor cell line Oli-neu might constitute an appropriate cell culture system to study molecular mechanisms or putative extracellular stimuli to functionally open Cx29 channels or hemi-channels.

  11. The Cx43-like connexin protein Cx40.8 is differentially localized during fin ontogeny and fin regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah V Gerhart

    Full Text Available Connexins (Cx are the subunits of gap junctions, membraneous protein channels that permit the exchange of small molecules between adjacent cells. Cx43 is required for cell proliferation in the zebrafish caudal fin. Previously, we found that a Cx43-like connexin, cx40.8, is co-expressed with cx43 in the population of proliferating cells during fin regeneration. Here we demonstrate that Cx40.8 exhibits novel differential subcellular localization in vivo, depending on the growth status of the fin. During fin ontogeny, Cx40.8 is found at the plasma membrane, but Cx40.8 is retained in the Golgi apparatus during regeneration. We next identified a 30 amino acid domain of Cx40.8 responsible for its dynamic localization. One possible explanation for the differential localization is that Cx40.8 contributes to the regulation of Cx43 in vivo, perhaps modifying channel activity during ontogenetic growth. However, we find that the voltage-gating properties of Cx40.8 are similar to Cx43. Together our findings reveal that Cx40.8 exhibits differential subcellular localization in vivo, dependent on a discrete domain in its carboxy terminus. We suggest that the dynamic localization of Cx40.8 differentially influences Cx43-dependent cell proliferation during ontogeny and regeneration.

  12. Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

    International Nuclear Information System (INIS)

    Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

    2015-01-01

    Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support

  13. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian; Wang, Xuhui; Wang, Guangchao; Wu, Junhua

    2013-01-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication

  14. Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

    Science.gov (United States)

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

    2016-06-15

    Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Connexin Hemichannels in Astrocytes

    DEFF Research Database (Denmark)

    Nielsen, Brian Skriver; Hansen, Daniel Bloch; Ransom, Bruce R.

    2017-01-01

    Astrocytes in the mammalian central nervous system are interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. These proteins may exist as hemichannels in the plasma membrane in the absence of a ‘docked’ counterpart on the neighboring cell. A variety of stimuli are repo...... selectivity. We expect that some, or all, of the controversies discussed here will be resolved by future research and sincerely hope that this review serves to motivate such clarifying investigations.......Astrocytes in the mammalian central nervous system are interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. These proteins may exist as hemichannels in the plasma membrane in the absence of a ‘docked’ counterpart on the neighboring cell. A variety of stimuli....... Published studies about astrocyte hemichannel behavior, however, have been highly variable and/or contradictory. The field of connexin hemichannel research has been complicated by great variability in the experimental preparations employed, a lack of highly specific pharmacological inhibitors...

  16. Correlations of differentially expressed gap junction connexins Cx26, Cx30, Cx32, Cx43 and Cx46 with breast cancer progression and prognosis.

    Directory of Open Access Journals (Sweden)

    Ivett Teleki

    Full Text Available Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models.The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively.Differential expression of Cx43 and Cx

  17. Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Steven C., E-mail: bug@uw.edu [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States); University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Kennedy, Brian K., E-mail: bkennedy@buckinstitute.org [University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945 (United States); Lampe, Paul D., E-mail: plampe@fhcrc.org [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

    2013-04-01

    An understanding of the molecular mechanism behind the arrhythmic phenotype associated with laminopathies has yet to emerge. A-type lamins have been shown to interact and sequester activated phospho-ERK1/2(pERK1/2) at the nucleus. The gap junction protein connexin43 (Cx43) can be phosphorylated by pERK1/2 on S279/282 (pS279/282), inhibiting intercellular communication. We hypothesized that without A-type lamins, pS279/282 Cx43 will increase due to inappropriate phosphorylation by pERK1/2, resulting in decreased gap junction function. We observed a 1.6-fold increase in pS279/282 Cx43 levels in Lmna{sup −/−} mouse embryonic fibroblasts (MEFs) compared to Lmna{sup +/+}, and 1.8-fold more pERK1/2 co-precipitated from Lmna{sup −/−} MEFs with Cx43 antibodies. We found a 3-fold increase in the fraction of non-nuclear pERK1/2 and a concomitant 2-fold increase in the fraction of pS279/282 Cx43 in Lmna{sup −/−} MEFs by immunofluorescence. In an assay of gap junctional function, Lmna{sup −/−} MEFs transferred dye to 60% fewer partners compared to Lmna{sup +/+} controls. These results are mirrored in 5–6 week-old Lmna{sup −/−} mice compared to their Lmna{sup +/+} littermates as we detect increased pS279/282 Cx43 in gap junctions by immunofluorescence and 1.7-fold increased levels by immunoblot. We conclude that increased pS279/282 Cx43 in the Lmna{sup −/−} background results in decreased cell communication and may contribute to the arrhythmic pathology in vivo. - Highlights: ► Connexin43 phosphorylation plays a role in laminopathy-associated conduction defects. ► Loss of A-type lamin activity results in release of pERK1/2 from the nucleus. ► Increased cytoplasmic localization of pERK1/2 acts to phosphorylate S279/282 of Cx43. ► Phosphorylation of S279/282 on Cx43 decreases gap junction activity in cell culture. ► Mice lacking A-type lamins have increased phosphorylation on S279/282 of Cx43.

  18. Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

    Science.gov (United States)

    Ram, Rashmi; Wescott, Andrew P; Varandas, Katherine; Dirksen, Robert T; Blaxall, Burns C

    2014-01-01

    Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

  19. Ultrastructure and regulation of lateralized connexin43 in the failing heart.

    Science.gov (United States)

    Hesketh, Geoffrey G; Shah, Manish H; Halperin, Victoria L; Cooke, Carol A; Akar, Fadi G; Yen, Timothy E; Kass, David A; Machamer, Carolyn E; Van Eyk, Jennifer E; Tomaselli, Gordon F

    2010-04-02

    Gap junctions mediate cell-to-cell electric coupling of cardiomyocytes. The primary gap junction protein in the working myocardium, connexin43 (Cx43), exhibits increased localization at the lateral membranes of cardiomyocytes in a variety of heart diseases, although the precise location and function of this population is unknown. To define the subcellular location of lateralized gap junctions at the light and electron microscopic level, and further characterize the biochemical regulation of gap junction turnover. By electron microscopy, we characterized gap junctions formed between cardiomyocyte lateral membranes in failing canine ventricular myocardium. These gap junctions were varied in structure and appeared to be extensively internalizing. Internalized gap junctions were incorporated into multilamellar membrane structures, with features characteristic of autophagosomes. Intracellular Cx43 extensively colocalized with the autophagosome marker GFP-LC3 when both proteins were exogenously expressed in HeLa cells, and endogenous Cx43 colocalized with GFP-LC3 in neonatal rat ventricular myocytes. Furthermore, a distinct phosphorylated form of Cx43, as well as the autophagosome-targeted form of LC3 (microtubule-associated protein light chain 3) targeted to lipid rafts in cardiac tissue, and both were increased in heart failure. Our data demonstrate a previously unrecognized pathway of gap junction internalization and degradation in the heart and identify a cellular pathway with potential therapeutic implications.

  20. Modulation of cardiac connexin-43 by omega-3 fatty acid ethyl-ester supplementation demonstrated in spontaneously diabetic rats

    Czech Academy of Sciences Publication Activity Database

    Radošinská, J.; Kurahara, L. H.; Hiraishi, K.; Viczenczová, C.; Egan Beňová, T.; Szeiffová Bačová, B.; Dosenko, V.; Navarová, J.; Obšitník, B.; Imanaga, I.; Soukup, Tomáš; Tribulová, N.

    2015-01-01

    Roč. 64, č. 6 (2015), s. 795-806 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 7AMB14SK123 Institutional support: RVO:67985823 Keywords : diabetes * omega-3 fatty acids * cardiac connexin-43 * PKC * ultrastructure Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

  1. Connexin 43 expression in human and mouse testes with impaired spermatogenesis

    Directory of Open Access Journals (Sweden)

    M Kotula-Balak

    2009-08-01

    Full Text Available Connexin 43 (Cx43 belongs to a family of proteins that form gap junction channels. The aim of this study was to examine the expression of Cx43 in the testis of a patient with Klinefelter’s syndrome and of mice with the mosaic mutation and a partial deletion in the long arm of the Y chromosome. These genetic disorders are characterized by the presence of numerous degenerated seminiferous tubules and impaired spermatogenesis. In mouse testes, the expression and presence of Cx43 were detected by means of immunohistochemistry and Western blot analysis, respectively. In testes of Klinefelter’s patient only immunoexpression of Cx43 was detected. Regardless of the species Cx43 protein was ubiquitously distributed in testes of reproductively normal males, whereas in those with testicular disorders either a weak intensity of staining or no staining within the seminiferous tubules was observed. Moderate to strong or very strong staining was confined to the interstitial tissue. In an immunoblot analysis of testicular homogenates Cx43 appeared as one major band of approximately 43 kDa. Our study adds three more examples of pathological gonads in which the absence or apparent decrease of Cx43 expression within the seminiferous tubules was found. A positive correlation between severe spermatogenic impairment and loss of Cx43 immunoreactivity observed in this study supports previous data that gap junctions play a crucial role in spermatogenesis. Strong Cx43 expression detected mostly in the interstitial tissue of the Klinefelter’s patient may presumably be of importance in sustaining Leydig cell metabolic activity. However, the role of gap junction communication in the control of Leydig cell function seems to be more complex than originally thought.

  2. Control of Vascular Smooth Muscle Cell Growth by Connexin 43

    Directory of Open Access Journals (Sweden)

    Chintamani eJoshi

    2012-06-01

    Full Text Available Connexin 43 (Cx43, the principal gap junction protein in vascular smooth muscle cells (VSMCs, regulates movement of ions and other signaling molecules through gap junction intercellular communication (GJIC and plays important roles in maintaining normal vessel function; however, many of the signaling mechanisms controlling Cx43 in VSMCs are not clearly described. The goal of this study was to investigate mechanisms of Cx43 regulation with respect to VSMC proliferation. Treatment of rat primary VSMCs with the cAMP analog 8Br-cAMP, the soluble guanylate cyclase (sGC stimulator BAY 41-2272 (BAY, or the Cx inducer diallyl disulfide (DADS significantly reduced proliferation after 72 h compared to vehicle controls. Bromodeoxyuridine uptake revealed reduction (p<.001 in DNA synthesis after 6 h and flow cytometry showed reduced (40% S phase cell numbers after 16 h in DADS-treated cells compared to controls. Cx43 expression significantly increased after 270 min treatment with 8Br-cAMP, 8Br-cGMP, BAY or DADS. Inhibition of PKA, PKG or PKC reversed 8Br-cAMP-stimulated increases in Cx43 expression, whereas only PKG or PKC inhibition reversed 8Br-cGMP- and BAY-stimulated increases in total Cx43. Interestingly, stimulation of Cx43 expression by DADS was not dependent on PKA, PKG or PKC. Using fluorescence recovery after photobleaching, only 8Br-cAMP or DADS increased GJIC with 8Br-cAMP mediated by PKC and DADS mediated by PKG. Further, DADS significantly increased phosphorylation at the MAPK-sensitive serine (Ser255 and Ser279, the cell cycle regulatory kinase-sensitive Ser262 and the PKC-sensitive Ser368 after 30 min while 8Br-cAMP significantly increased phosphorylation only at Ser279 compared to controls. This study demonstrates that 8Br-cAMP- and DADS-enhanced GJIC rather than Cx43 expression and/or phosphorylation plays an important role in regulation of VSMC proliferation and provides new insights into the growth-regulatory capacities of Cx43 in VSMCs.

  3. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

    Science.gov (United States)

    Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

    2016-04-01

    Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to

  4. Connexin 43 Communication Channels in Follicular Dendritic Cell Development and in Follicular Lymphomas

    Directory of Open Access Journals (Sweden)

    Hajnalka Rajnai

    2015-01-01

    Full Text Available Follicular dendritic cells (FDC show homo- and heterocellular metabolic coupling through connexin 43 (Cx43 gap junctions and support B cell selection and maturation in germinal centers. In follicular lymphomas B cells escape apoptosis while FDC develop abnormally. Here we tested Cx43 channels in reactive FDC development and follicular lymphomas. In culture, the treatment of FDC-B cell clusters (resembling to “ex vivo” germinal centers with Gap27 peptide, mimicking the 2nd extracellular loop of Cx43 protein, significantly impaired FDC-B cell cluster formation and cell survival. In untreated cultures of intact clusters, cell proliferation showed a moderate reduction. In tissues, Cx43 protein levels run parallel with the density of FDC both in reactive germinal centers and in malformed follicles of follicular lymphomas and showed strong upregulation in newly generated and/or degrading bi-/multinuclear FDC of rudimentary processes. However, the inverse correlation between Cx43 expression and B cell proliferation seen in reactive germinal centers was not detected in follicular lymphomas. Furthermore, Cx43 levels were not associated with either lymphoma grade or bone marrow involvement. Our results suggest that Cx43 channels are critical in FDC and “ex vivo” germinal center development and in the persistence of FDC in follicular lymphomas but do not affect tumor progression.

  5. Gap junction connexins in female reproductive organs: implications for women's reproductive health.

    Science.gov (United States)

    Winterhager, Elke; Kidder, Gerald M

    2015-01-01

    Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This review provides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women's reproductive health. No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs, much of the cited information comes from research with genetically modified mice. In some cases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to non-channel roles. Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth

  6. Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

    Science.gov (United States)

    Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

    2016-10-01

    Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (PLucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

  7. Histone deacetylase inhibition reduces cardiac Connexin43 expression and gap junction communication

    Directory of Open Access Journals (Sweden)

    Qin eXu

    2013-04-01

    Full Text Available Histone deactylase (HDAC inhibitors are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDAC inhibitors on the functional expression of cardiac gap junctions (GJ are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA and vorinostat (VOR on functional GJ expression in ventricular cardiomyocytes. The effects of HDAC inhibition on connexin43 (Cx43 expression and functional GJ assembly were examined in primary cultured neonatal mouse ventricular myocytes. TSA and VOR reduced Cx43 mRNA, protein expression, and immunolocalized Cx43 GJ plaque area within ventricular myocyte monolayer cultures in a dose-dependent manner. Chromatin-immunoprecipitation experiments revealed altered protein interactions with the Cx43 promoter. VOR also altered the phosphorylation state of several key regulatory Cx43 phospho-serine sites. Patch clamp analysis revealed reduced electrical coupling between isolated ventricular myocyte pairs, altered transjunctional voltage-dependent inactivation kinetics, and steady state junctional conductance inactivation and recovery relationships. Single GJ channel conductance was reduced to 54 pS only by maximum inhibitory doses of TSA (>= 100 nM. These two hydroxamate pan-HDAC inhibitors exert multiple levels of regulation on ventricular GJ communication by altering Cx43 expression, GJ area, post-translational modifications (e.g. phosphorylation, acetylation, gating, and channel conductance. Although a 50% downregulation of Cx43 GJ communication alone may not be sufficient to slow ventricular conduction or induce arrhythmias, the development of class-selective HDAC inhibitors may help avoid the potential negative cardiovascular effects of pan-HDACI.

  8. Na,K-ATPase regulates intercellular communication in the vascular wall via cSrc kinase dependent connexin43 phosphorylation

    DEFF Research Database (Denmark)

    Hangaard, Lise; Bouzinova, Elena; Stæhr, Christian Albeck

    2017-01-01

    Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na-K-ATPase. The Na-K-ATPase is therefore important for synchronized VSMC oscillatory activity, i.e., vasomotion. The signaling between the Na-K-ATPase and gap junctions is unknown. We...... coupling in rat mesenteric small arteries in vitro. Phosphorylation of cSrc kinase and connexin43 (Cx43) were semiquantified by Western blotting. Micromole concentration of ouabain reduced the amplitude of norepinephrine-induced vasomotion and desynchronized Ca2+ transients in VSMC in the arterial wall...

  9. Different expressions of connexin 43 and 32 in the fibroblasts of human dental pulp.

    Science.gov (United States)

    Ibuki, N; Yamaoka, Y; Sawa, Y; Kawasaki, T; Yoshida, S

    2002-06-01

    The expression and localization of gap junctional proteins connexin (Cx) 26, 32, and 43 was examined in human dental pulp. Dental pulp tissues were obtained from human third molars immediately after extraction. Some pulp tissues were used for cell culture, and the rest for histological observations. Immunostaining for cultured dental pulp fibroblasts (DPFs) showed that Cx32 and 43 were expressed in human DPFs, and proteins corresponding to 27 (Cx32) and 43kDa (Cx43) were identified by Western blot analysis. Immunostaining for tissue sections showed that the expression of Cx32 and 43 was observed in the entire region of the pulp and further strong expression of Cx32 was established beneath the cell-rich zone. Considering the close relationship between Cx types and cell functions, the results indicate that DPFs beneath the cell-rich zone may have specific, Cx32-related functions. The cell rich zone is thought to contain progenitor odontoblasts that can be induced to differentiate into mature odontoblasts in response to wounding. Therefore, it may be hypothesized that DPFs just beneath the cell-rich zone produce proteins and induce odontoblast differentiation from the cells in the cell-rich zone.

  10. Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis.

    Science.gov (United States)

    Tsuchida, Shinji; Arai, Yuji; Kishida, Tsunao; Takahashi, Kenji A; Honjo, Kuniaki; Terauchi, Ryu; Inoue, Hiroaki; Oda, Ryo; Mazda, Osam; Kubo, Toshikazu

    2013-04-01

    The objective of the present study was to determine whether the expression of connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen-induced arthritis (CIA) were examined by in vivo electroporation method. LPS markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43 suppressing the over-expression of pro-inflammatory cytokines and the chemokine. Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and significantly reduced histological arthritis scores and radiographic scores. In histological appearance of rat ankle joints, siCx43 treatment significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive (osteoclast-like) cells. These findings indicated that siCx43 had anti-inflammatory effects in rat FLS and efficiently inhibited the development of CIA. Cx43 may play an important role in the pathophysiology of RA, and may be a potential target molecule for novel RA therapies. Copyright © 2012 Orthopaedic Research Society.

  11. Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

    Science.gov (United States)

    Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

    2016-01-01

    Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

    Science.gov (United States)

    Szilvásy-Szabó, Anett; Varga, Edina; Beliczai, Zsuzsa; Lechan, Ronald M; Fekete, Csaba

    2017-10-15

    Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of α-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of β-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among α-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Katsuhisa Masaki

    Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS

  14. Effects of androgen on immunohistochemical localization of androgen receptor and Connexin 43 in mouse ovary.

    Science.gov (United States)

    Yang, Mei; Li, Jianhua; An, Yulin; Zhang, Shuiwen

    2015-10-01

    Androgens have essential roles in the regulation of follicular development and female fertility. Androgen excess is the leading defect in polycystic ovary syndrome (PCOS) patients and involved in the ovarian dysfunction. The aim of this study was to elucidate the regarding regulatory role of androgen in the follicular development of female mouse. Immunohistochemical staining and Western blot analyses were performed to detect androgen receptor (AR) and Connexin 43 (Cx43) expression in ovaries from both control and testosterone-treated group mice. In this study, localizations of AR and Cx43 were dramatically altered in testosterone-treated mouse ovaries. In addition, AR expression was significantly increased, whereas Cx43 expression was markedly decreased after testosterone treatment. Alterations of AR and Cx43 expression by testosterone with concomitant reduction of MII oocytes. Overall, these results suggest the involvement of androgen in the regulation of AR and Cx43 localizations in mouse ovary. Alterations of AR and Cx43 expression by testosterone may affect normal folliculogenesis. Together these findings will enable us to begin understanding the important roles of AR and Cx43 actions in the regulation of follicular development, as well as providing insights into the role of AR and Cx43 actions in the androgen-associated reproductive diseases such as PCOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Molecular cloning and evolutionary analysis of the GJA1 (connexin43) gene from bats (Chiroptera).

    Science.gov (United States)

    Wang, Li; Li, Gang; Wang, Jinhong; Ye, Shaohui; Jones, Gareth; Zhang, Shuyi

    2009-04-01

    Gap junction protein connexin43 (Cx43), encoded by the GJA1 gene, is the most abundant connexin in the cardiovascular system and was reported as a crucial factor maintaining cardiac electrical conduction, as well as having a very important function in facilitating the recycling of potassium ions from hair cells in the cochlea back into the cochlear endolymph during auditory transduction processes. In mammals, bats are the only taxon possessing powered flight, placing exceptional demand on many organismal processes. To meet the demands of flying, the hearts of bats show many specialties. Moreover, ultrasonic echolocation allows bat species to orientate and often detect and locate food in darkness. In this study, we cloned the full-length coding region of GJA1 gene from 12 different species of bats and obtained orthologous sequences from other mammals. We used the maximum likelihood method to analyse the evolution of GJA1 gene in mammals and the lineage of bats. Our results showed this gene is much conserved in mammals, as well as in bats' lineage. Compared with other mammals, we found one private amino acid substitution shared by bats, which is located on the inner loop domain, as well as some species-specific amino acid substitutions. The evolution rate analyses showed the signature of purifying selection on not only different classification level lineages but also the different domains and amino acid residue sites of this gene. Also, we suggested that GJA1 gene could be used as a good molecular marker to do the phylogenetic reconstruction.

  16. Cardiac Connexin-43 and PKC Signaling in Rats With Altered Thyroid Status Without and With Omega-3 Fatty Acids Intake

    Czech Academy of Sciences Publication Activity Database

    Szeiffová Bačová, B.; Egan Beňová, T.; Viczenczová, C.; Soukup, Tomáš; Rauchová, Hana; Pavelka, Stanislav; Knezl, V.; Barančík, M.; Tribulová, N.

    2016-01-01

    Roč. 65, Suppl.1 (2016), S77-S90 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * Connexin-43 * omega-3 polyunsaturated fatty acids Subject RIV: ED - Physiology Impact factor: 1.461, year: 2016

  17. Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment.

    Science.gov (United States)

    Pecoraro, Michela; Rodríguez-Sinovas, Antonio; Marzocco, Stefania; Ciccarelli, Michele; Iaccarino, Guido; Pinto, Aldo; Popolo, Ada

    2017-10-11

    The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca 2+ ] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca 2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca 2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered.

  18. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    International Nuclear Information System (INIS)

    Talhouk, Rabih S.; Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania; El-Sabban, Marwan E.

    2013-01-01

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

  19. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    Energy Technology Data Exchange (ETDEWEB)

    Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

    2013-12-10

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

  20. Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

    Directory of Open Access Journals (Sweden)

    Harissios Vliagoftis

    2014-01-01

    Full Text Available Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

  1. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin 43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model

    Energy Technology Data Exchange (ETDEWEB)

    Carette, Diane [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Perrard, Marie-Hélène, E-mail: marie-helene.durand@ens-lyon.fr [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Prisant, Nadia [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Gilleron, Jérome; Pointis, Georges [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); Segretain, Dominique [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Durand, Philippe [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Kallistem SAS Ecole Normale Supérieure de Lyon, Lyon (France)

    2013-04-01

    Exposure to toxic metals, specifically those belonging to the nonessential group leads to human health defects and among them reprotoxic effects. The mechanisms by which these metals produce their negative effects on spermatogenesis have not been fully elucidated. By using the Durand's validated seminiferous tubule culture model, which mimics the in vivo situation, we recently reported that concentrations of hexavalent chromium, reported in the literature to be closed to that found in the blood circulation of men, increase the number of germ cell cytogenetic abnormalities. Since this metal is also known to affect cellular junctions, we investigated, in the present study, its potential influence on the Sertoli cell barrier and on junctional proteins present at this level such as connexin 43, claudin-11 and N-cadherin. Cultured seminiferous tubules in bicameral chambers expressed the three junctional proteins and ZO-1 for at least 12 days. Exposure to low concentrations of chromium (10 μg/l) increased the trans-epithelial resistance without major changes of claudin-11 and N-cadherin expressions but strongly delocalized the gap junction protein connexin 43 from the membrane to the cytoplasm of Sertoli cells. The possibility that the hexavalent chromium-induced alteration of connexin 43 indirectly mediates the effect of the toxic metal on the blood–testis barrier dynamic is postulated. - Highlights: ► Influence of Cr(VI) on the Sertoli cell barrier and on junctional proteins ► Use of cultured seminiferous tubules in bicameral chambers ► Low concentrations of Cr(VI) (10 μg/l) altered the trans-epithelial resistance. ► Cr(VI) did not alter claudin-11 and N-cadherin. ► Cr(VI) delocalized connexin 43 from the membrane to the cytoplasm of Sertoli cells.

  2. Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria

    Directory of Open Access Journals (Sweden)

    Mariana C. Fiori

    2017-11-01

    Full Text Available In addition to gap junctional channels that mediate cell-to-cell communication, connexins form hemichannels that are present at the plasma membrane. Since hemichannels are permeable to small hydrophilic compounds, including metabolites and signaling molecules, their abnormal opening can cause or contribute to cell damage in disorders such as cardiac infarct, stroke, deafness, skin diseases, and cataracts. Therefore, hemichannels are potential pharmacological targets. A few aminoglycosides, well-known broad-spectrum antibiotics, have been shown to inhibit hemichannels. Here, we tested several commercially available aminoglycosides for inhibition of human connexin hemichannels using a cell-based bacterial growth complementation assay that we developed recently. We found that kanamycin A, kanamycin B, geneticin, neomycin, and paromomycin are effective inhibitors of hemichannels formed by connexins 26, 43, and 46 (Cx26, Cx43, and Cx46. Because of the >70 years of clinical experience with aminoglycosides and the fact that several of the aminoglycosides tested here have been used in humans, they are promising starting points for the development of effective connexin hemichannel inhibitors.

  3. Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123)

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Stahlhut, Martin; Mohammed, Shabaz

    2006-01-01

    Previous studies suggest that dephosphorylation of connexin43 (Cx43) is related to uncoupling of gap junction communication, which plays an important role in the genesis of ischemia-induced ventricular tachycardia. We studied changes in Cx43 phosphorylation during global ischemia in the absence...... and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass...... of ischemia, the critical time interval where gap junction uncoupling occurs, Ser297 and Ser368 also became fully dephosphorylated. During the same time period, all untreated hearts developed asystole. Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed...

  4. Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

    Science.gov (United States)

    Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

    2016-07-01

    Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

  5. Connexin 43 Channels are Essential for Normal Bone Structure and Osteocyte Viability

    Science.gov (United States)

    Xu, Huiyun; Gu, Sumin; Riquelme, Manuel A.; Burra, Sirisha; Callaway, Danielle; Cheng, Hongyun; Guda, Teja; Schmitz, James; Fajardo, Roberto J.; Werner, Sherry L.; Zhao, Hong; Shang, Peng; Johnson, Mark L.; Bonewald, Lynda F.; Jiang, Jean X.

    2014-01-01

    Connexin (Cx) 43 serves important roles in bone function and development. Targeted deletion of Cx43 in osteoblasts or osteocytes leads to increased osteocyte apoptosis, osteoclast recruitment, and reduced biomechanical properties. Cx43 forms both gap junction channels and hemichannels, which mediate the communication between adjacent cells or between cell and extracellular environments, respectively. Two transgenic mouse models driven by a DMP1 promoter with the overexpression of dominant negative Cx43 mutants were generated to dissect the functional contribution of Cx43 gap junction channels and hemichannels in osteocytes. The R76W mutant blocks gap junction channel, but not hemichannel function, and the Δ130-136 mutant inhibits activity of both types of channels. Δ130-136 mice showed a significant increase in bone mineral density compared to WT and R76W mice. MicroCT analyses revealed a significant increase in total tissue and bone area in midshaft cortical bone of Δ130-136 mice. The bone marrow cavity was expanded, whereas the cortical thickness was increased and associated with increased bone formation along the periosteal area. However, there is no significant alteration in the structure of trabecular bone. Histologic sections of the midshaft showed increased apoptotic osteocytes in Δ130-136, but not in WT and R76W, mice which correlated with altered biomechanical and estimated bone material properties. Osteoclasts were increased along the endocortical surface in both transgenic mice with a greater effect in Δ130-136 mice which likely contributed to the increased marrow cavity. Interestingly, the overall expression of serum bone formation and resorption markers were higher in R76W mice. These findings suggest that osteocytic Cx43 channels play distinctive roles in the bone; hemichannels play a dominant role in regulating osteocyte survival, endocortical bone resorption and periosteal apposition, and gap junction communication is involved in the process of

  6. Connexin43 hemichannels contributes to the disassembly of cell junctions through modulation of intracellular oxidative status

    Directory of Open Access Journals (Sweden)

    Yuan Chi

    2016-10-01

    Full Text Available Connexin (Cx hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca2+-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance. These changes were preceded by an activation of Cx43 hemichannels, as revealed by extracellular efflux of ATP and intracellular influx of Lucifer Yellow. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA greatly attenuated the disassembly of cell junctions. Further analysis using fetal fibroblasts derived from Cx43 wide-type (Cx43+/+, heterozygous (Cx43+/- and knockout (Cx43-/- littermates showed that Cx43-positive cells (Cx43+/+ exhibited more dramatic changes in cell shape, F-actin, and cadherin in response to Ca2+ depletion, as compared to Cx43-null cells (Cx43-/-. Consistently, these cells had higher level of protein carbonyl modification and phosphorylation, and much stronger activation of P38 and JNK. Hemichannel opening led to extracellular loss of the major antioxidant glutathione (GSH. Supplement of cells with exogenous GSH or inhibition of oxidative sensitive kinases largely prevented the above-mentioned changes. Taken together, our study indicates that Cx43 hemichannels promote the disassembly of cell junctions through regulation of intracellular oxidative status.

  7. Connexins and Disease

    DEFF Research Database (Denmark)

    Delmar, Mario; Laird, Dale W; Naus, Christian C

    2017-01-01

    Inherited or acquired alterations in the structure and function of connexin proteins have long been associated with disease. In the present work, we review current knowledge on the role of connexins in diseases associated with the heart, nervous system, cochlea, and skin, as well as cancer...... of connexins are fundamental components in the pathophysiology of multiple connexin related disorders, many of them highly debilitating and life threatening. Improved understanding of connexin biology has the potential to advance our understanding of mechanisms, diagnosis, and treatment of disease....

  8. Proinflammatory cytokines downregulate connexin 43-gap junctions via the ubiquitin-proteasome system in rat spinal astrocytes.

    Science.gov (United States)

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

    2015-09-04

    Astrocytic gap junctions formed by connexin 43 (Cx43) are crucial for intercellular communication between spinal cord astrocytes. Various neurological disorders are associated with dysfunctional Cx43-gap junctions. However, the mechanism modulating Cx43-gap junctions in spinal astrocytes under pathological conditions is not entirely clear. A previous study showed that treatment of spinal astrocytes in culture with pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased both Cx43 expression and gap junction intercellular communication (GJIC) via a c-jun N-terminal kinase (JNK)-dependent pathway. The current study further elaborates the intracellular mechanism that decreases Cx43 under an inflammatory condition. Cycloheximide chase analysis revealed that TNF-α (10 ng/ml) alone or in combination with IFN-γ (5 ng/ml) accelerated the degradation of Cx43 protein in cultured spinal astrocytes. The reduction of both Cx43 expression and GJIC induced by a mixture of TNF-α and IFN-γ were blocked by pretreatment with proteasome inhibitors MG132 (0.5 μM) and epoxomicin (25 nM), a mixture of TNF-α and IFN-γ significantly increased proteasome activity and Cx43 ubiquitination. In addition, TNF-α and IFN-γ-induced activation of ubiquitin-proteasome systems was prevented by SP600125, a JNK inhibitor. Together, these results indicate that a JNK-dependent ubiquitin-proteasome system is induced under an inflammatory condition that disrupts astrocytic gap junction expression and function, leading to astrocytic dysfunction and the maintenance of the neuroinflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.

    Science.gov (United States)

    Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck

    2008-12-01

    One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

  10. Linoleic Acid Permeabilizes Gastric Epithelial Cells by Increasing Connexin43 Levels in the Cell Membrane Via a GPR40- and Akt-Dependent Mechanism

    Science.gov (United States)

    Puebla, Carlos; Cisterna, Bruno A.; Salas, Daniela P.; Delgado-López, Fernando; Lampe, Paul D.; Sáez, Juan C.

    2016-01-01

    Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC of similar intensity and additive with LA-induced change. Treatment with a CD36 blocker or transfection with siRNA-GPR120 maintain the LA-induced Cx HC activity. However, cells transfected with siRNA-GPR40 did not show LA-induced Cx HC activity but activity was increased upon exposure to DCFS, confirming the presence of activatable Cx HCs in the cell membrane. Treatment with AKTi (Akt inhibitor) abrogated the LA-induced Cx HC activity. In HeLa cells transfected with Cx43 (HeLa-Cx43), LA induced phosphorylation of surface Cx43 at serine 373 (S373), site for Akt phosphorylation. HeLa-Cx43 but not HeLa-Cx43 cells with a S373A mutation showed a LA-induced Cx HC activity directly related to an increase in cell surface Cx43 levels. Thus, the increase in membrane permeability induced by LA is mediated by an intracellular signaling pathway activated by GPR40 that leads to an increase in membrane levels of Cx43 phosphorylated at serine 373 via Akt. PMID:26869446

  11. Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation

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    Hongyan Xie

    2017-01-01

    Full Text Available Connexin 43 (Cx43 is the major component protein in astrocytic gap junction communication. Recent studies have shown the cellular processes of gap junction internalization and degradation, but many details remain unknown. This study investigated the distribution of Cx43 and its mechanism after ischemic insult. Astrocyte culture system and a model of ischemia/reperfusion (IR or oxygen-glucose deprivation and reoxygenation (OGDR were established. Cx43 distribution was observed by laser scanning confocal microscopy under different cultivation conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and MAPRE1 (microtubule-associated protein RP/EB family member 1 expression at different time points. The total number of Cx43 was unchanged in the normal and IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were significantly greater than that of the normal group. Particles in the cytoplasm were significantly fewer after endocytosis was blocked by dynasore. There was no difference among the groups at each time point regarding protein or gene expression of MAPRE1. We concluded that internalization of Cx43 into the cytoplasm occurred during ischemia, which was partially mediated through endocytosis, not by the change of Cx43 quantity. Moreover, internalization was not related to microtubule transport.

  12. Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo.

    Science.gov (United States)

    Mancuso, M; Pasquali, E; Leonardi, S; Rebessi, S; Tanori, M; Giardullo, P; Borra, F; Pazzaglia, S; Naus, C C; Di Majo, V; Saran, A

    2011-11-10

    Ionizing radiation is a genotoxic agent and human carcinogen. Recent work has questioned long-held dogmas by showing that cancer-associated genetic alterations occur in cells and tissues not directly exposed to radiation, questioning the robustness of the current system of radiation risk assessment. In vitro, diverse mechanisms involving secreted soluble factors, gap junction intercellular communication (GJIC) and oxidative metabolism are proposed to mediate these indirect effects. In vivo, the mechanisms behind long-range 'bystander' responses remain largely unknown. Here, we investigate the role of GJIC in propagating radiation stress signals in vivo, and in mediating radiation-associated bystander tumorigenesis in mouse central nervous system using a mouse model in which intercellular communication is downregulated by targeted deletion of the connexin43 (Cx43) gene. We show that GJIC is critical for transmission of oncogenic radiation damage to the non-targeted cerebellum, and that a mechanism involving adenosine triphosphate release and upregulation of Cx43, the major GJIC constituent, regulates transduction of oncogenic damage to unirradiated tissues in vivo. Our data provide a novel hypothesis for transduction of distant bystander effects and suggest that the highly branched nervous system, similar to the vascular network, has an important role.

  13. Air-Stimulated ATP Release from Keratinocytes Occurs through Connexin Hemichannels

    Science.gov (United States)

    Barr, Travis P.; Albrecht, Phillip J.; Hou, Quanzhi; Mongin, Alexander A.; Strichartz, Gary R.; Rice, Frank L.

    2013-01-01

    Cutaneous ATP release plays an important role in both epidermal stratification and chronic pain, but little is known about ATP release mechanisms in keratinocytes that comprise the epidermis. In this study, we analyzed ATP release from cultured human neonatal keratinocytes briefly exposed to air, a process previously demonstrated to trigger ATP release from these cells. We show that exposing keratinocytes to air by removing media for 15 seconds causes a robust, long-lasting ATP release. This air-stimulated ATP release was increased in calcium differentiated cultures which showed a corresponding increase in connexin 43 mRNA, a major component of keratinocyte hemichannels. The known connexin hemichannel inhibitors 1-octanol and carbenoxolone both significantly reduced air-stimulated ATP release, as did two drugs traditionally used as ABC transporter inhibitors (glibenclamide and verapamil). These same 4 inhibitors also prevented an increase in the uptake of a connexin permeable dye induced by air exposure, confirming that connexin hemichannels are open during air-stimulated ATP release. In contrast, activity of the MDR1 ABC transporter was reduced by air exposure and the drugs that inhibited air-stimulated ATP release had differential effects on this transporter. These results indicate that air exposure elicits non-vesicular release of ATP from keratinocytes through connexin hemichannels and that drugs used to target connexin hemichannels and ABC transporters may cross-inhibit. Connexins represent a novel, peripheral target for the treatment of chronic pain and dermatological disease. PMID:23457608

  14. Inhibition of Connexin 26/43 and Extracellular-Regulated Kinase Protein Plays a Critical Role in Melatonin Facilitated Gap Junctional Intercellular Communication in Hydrogen Peroxide-Treated HaCaT Keratinocyte Cells

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    Hyo-Jung Lee

    2012-01-01

    Full Text Available Though melatonin was known to regulate gap junctional intercellular communication (GJIC in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2- treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H2O2 at 300 μM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26 and connexin 43 (Cx43 at mRNA and protein levels, but not that of connexin 30 (Cx30 in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μM and vitamin C (10 μg/mL significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

  15. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

    Science.gov (United States)

    Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

    2006-09-01

    Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

  16. Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.

    Science.gov (United States)

    Stehberg, Jimmy; Moraga-Amaro, Rodrigo; Salazar, Christian; Becerra, Alvaro; Echeverría, Cesar; Orellana, Juan A; Bultynck, Geert; Ponsaerts, Raf; Leybaert, Luc; Simon, Felipe; Sáez, Juan C; Retamal, Mauricio A

    2012-09-01

    Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, d-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.

  17. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

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    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  18. Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.

    NARCIS (Netherlands)

    Paznekas, W.A.; Boyadjiev, S.A.; Shapiro, R.E.; Daniëls, O.; Wollnik, B.; Keegan, C.E.; Innis, J.W.; Dinulos, M.B.; Christian, C.; Hannibal, M.C.; Jabs, E.W.

    2003-01-01

    Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance

  19. Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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    Chen Li

    Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

  20. Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

    Science.gov (United States)

    Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

    2014-01-17

    Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

  1. Roles of gap junctions, connexins and pannexins in epilepsy

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    Shanthini eMylvaganam

    2014-05-01

    Full Text Available Enhanced gap junctional communication (GJC between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In addition, the hippocampal sharp wave ripple complexes, associated with learning and seizures, are diminished by GJC blocking agents. Although gap junctional blocking drugs inhibit experimental seizures, they all have other nonspecific actions. Besides interneuronal GJC between dendrites, inter-axonal and inter-glial GJC is also considered important for seizure generation. Interestingly, in most studies of cerebral tissue from animal seizure models and from human patients with epilepsy, there is up-regulation of glial, but not neuronal gap junctional mRNA and protein. Significant changes in the expression and post-translational modification of the astrocytic connexin Cx43, and Panx1 were observed in an in vitro Co++ seizure model, further supporting a role for glia in seizure-genesis, although the reasons for this remain unclear. Further suggesting an involvement of astrocytic GJC in epilepsy, is the fact that the expression of astrocytic Cx mRNAs (Cxs 30 and 43 is several fold higher than that of neuronal Cx mRNAs (Cxs 36 and 45, and the number of glial cells outnumber neuronal cells in mammalian hippocampal and cortical tissue. Pannexin expression is also increased in both animal and human epileptic tissues. Specific Cx43 mimetic peptides, Gap 27 and SLS, inhibit the docking of astrocytic connexin Cx43 proteins from forming intercellular gap junctions, diminishing spontaneous seizures. Besides GJs, Cx membrane hemichannels in glia and Panx membrane channels in neurons and glia are also inhibited by gap junctional pharmacological blockers. Although there is no doubt that connexin-based gap junctions and hemichannels, and pannexin-based membrane channels are related to epilepsy, the specific details of how they are involved and how we can modulate their function for therapeutic purposes remain to

  2. Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

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    Zahra Moinfar

    Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

  3. Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate

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    Anna Hejmej

    2013-01-01

    Full Text Available To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR and connexin 43 (Cx43 in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20, neonatal (PD2, and prepubertal (PD90 exposure to an antiandrogen flutamide (50 mg/kg bw. In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages.

  4. Cumulus expansion, nuclear maturation and connexin 43, cyclooxygenase-2 and FSH receptor mRNA expression in equine cumulus-oocyte complexes cultured in vitro in the presence of FSH and precursors for hyaluronic acid synthesis

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    Aiudi Giulio

    2004-06-01

    Full Text Available Abstract The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH and precursors for hyaluronic acid synthesis. Equine cumulus-oocyte complexes (COC were cultured in a control defined medium supplemented with eFSH (0 to 5 micrograms/ml, Fetal Calf Serum (FCS, precursors for hyaluronic acid synthesis or glutamine according to the experiments. After in vitro maturation, the cumulus expansion rate was increased with 1 microgram/ml eFSH, and was the highest with 20% FCS. It was not influenced by precursors for hyaluronic acid synthesis or glutamine. The expression of transcripts related to cumulus expansion was analyzed in equine cumulus cells before maturation, and after in vivo and in vitro maturation, by using reverse transcription-polymerase chain reaction (RT-PCR with specific primers. Connexin 43, cyclooxygenase-2 (COX-2 and FSH receptor (FSHr mRNA were detected in equine cumulus cells before and after maturation. Their level did not vary during in vivo or in vitro maturation and was influenced neither by FSH nor by precursors for hyaluronic acid synthesis. Results indicate that previously reported regulation of connexin 43 and COX-2 proteins during equine COC maturation may involve post-transcriptional mechanisms.

  5. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian

    2013-04-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. © 2012 Elsevier Inc. All rights reserved.

  6. 29 CFR 785.43 - Medical attention.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Medical attention. 785.43 Section 785.43 Labor Regulations..., Medical Attention, Civic and Charitable Work, and Suggestion Systems § 785.43 Medical attention. Time spent by an employee in waiting for and receiving medical attention on the premises or at the direction...

  7. Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle.

    Science.gov (United States)

    Clasadonte, Jerome; Scemes, Eliana; Wang, Zhongya; Boison, Detlev; Haydon, Philip G

    2017-09-13

    Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Connexin 43 Gene Therapy Delivered by Polymer-Modified Salmonella in Murine Tumor Models

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    Wei-Kuang Wang

    2014-04-01

    Full Text Available The use of preferentially tumor-targeting bacteria as vectors is one of the most innovative approaches for the treatment of cancer. This method is based on the observation that some obligate or facultative anaerobic bacteria are capable of selectively multiplying in tumors and inhibiting their growth. Previously, we found that the tumor-targeting efficiency of Salmonella could be modulated by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride (PAH, and these organisms are designated PAH-S.C. (S. choleraesuis. PAH can provide a useful platform for the chemical modification of Salmonella, perhaps by allowing a therapeutic gene to bind to tumor-targeting Salmonella. This study aimed to investigate the benefits of the use of PAH-S.C. for gene delivery. To evaluate this modulation, the invasion activity and gene transfer of DNA-PAH-S.C. were measured in vitro and in vivo. Treatment with PAH-S.C. carrying a tumor suppressor gene (connexin 43 resulted in inhibition of tumor growth, which suggested that tumor-targeted gene therapy using PAH-S.C. carrying a therapeutic gene could exert antitumor activities. This technique represents a promising strategy for the treatment of tumors.

  9. 43 CFR 29.11 - Investment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Investment. 29.11 Section 29.11 Public... Investment. (a) The monies accumulated in the Fund shall be prudently invested in the following types of... investment advisor or custodian to the Fund, or their affiliates may be purchased or held by the Fund. (3...

  10. 43 CFR 418.29 - Project management.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Project management. 418.29 Section 418.29... INTERIOR OPERATING CRITERIA AND PROCEDURES FOR THE NEWLANDS RECLAMATION PROJECT, NEVADA Enforcement § 418.29 Project management. In addition to the provisions of § 418.28, if the District is found to be...

  11. Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma‑associated epileptic discharge (Review).

    Science.gov (United States)

    Dong, Hui; Zhou, Xing-Wang; Wang, Xiang; Yang, Yuan; Luo, Jie-Wen; Liu, Yan-Hui; Mao, Qing

    2017-12-01

    Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi‑channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43‑associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43‑gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor‑inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43‑GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma‑associated seizure. Thus, Cx43 may take part in the onset and development of glioma‑associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi‑channels exert enduring effects in the promotion of glioma‑associated epileptic release through direct mass effects and change of the tumor microenvironment

  12. Connexin 30 expression and frequency of connexin heterogeneity in astrocyte gap junction plaques increase with age in the rat retina.

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    Hussein Mansour

    Full Text Available We investigated age-associated changes in retinal astrocyte connexins (Cx by assaying Cx numbers, plaque sizes, protein expression levels and heterogeneity of gap junctions utilizing six-marker immunohistochemistry (IHC. We compared Wistar rat retinal wholemounts in animals aged 3 (young adult, 9 (middle-aged and 22 months (aged. We determined that retinal astrocytes have gap junctions composed of Cx26, -30, -43 and -45. Cx30 was consistently elevated at 22 months compared to younger ages both when associated with parenchymal astrocytes and vascular-associated astrocytes. Not only was the absolute number of Cx30 plaques significantly higher (P<0.05 but the size of the plaques was significantly larger at 22 months compared to younger ages (p<0.05. With age, Cx26 increased significantly initially, but returned to basal levels; whereas Cx43 expression remained low and stable with age. Evidence that astrocytes alter connexin compositions of gap junctions was demonstrated by the significant increase in the number of Cx26/Cx45 gap junctions with age. We also found gap junctions comprised of 1, 2, 3 or 4 Cx proteins suggesting that retinal astrocytes use various connexin protein combinations in their gap junctions during development and aging. These data provides new insight into the dynamic and extensive Cx network utilized by retinal astrocytes for communication within both the parenchyma and vasculature for the maintenance of normal retinal physiology with age. This characterisation of the changes in astrocytic gap junctional communication with age in the CNS is crucial to the understanding of physiological aging and age-related neurodegenerative diseases.

  13. The dynamics of connexin expression, degradation and localisation are regulated by gonadotropins during the early stages of in vitro maturation of swine oocytes.

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    Nicolas Santiquet

    Full Text Available Gap junctional communication (GJC plays a primordial role in oocyte maturation and meiotic resumption in mammals by directing the transfer of numerous molecules between cumulus cells and the oocyte. Gap junctions are made of connexins (Cx, proteins that regulate GJC in numerous ways. Understanding the dynamic regulation of connexin arrangements during in vitro maturation (IVM could provide a powerful tool for controlling meiotic resumption and consequently in vitro development of fully competent oocytes. However, physiological events happening during the early hours of IVM may still be elucidated. The present study reports the dynamic regulation of connexin expression, degradation and localization during this stage. Cx43, Cx45 and Cx60 were identified as the main connexins expressed in swine COC. Cx43 and Cx45 transcripts were judged too static to be a regulator of GJC, while Cx43 protein expression was highly responsive to gonadotropins, suggesting that it might be the principal regulator of GJC. In addition, the degradation of Cx43 expressed after 4.5 h of IVM in response to equine chorionic gonadotropin appeared to involve the proteasomal complex. Cx43 localisation appeared to be associated with GJC. Taken together, these results show for the first time that gonadotropins regulate Cx43 protein expression, degradation and localisation in porcine COC during the first several hours of IVM. Regulation of Cx43 may in turn, via GJC, participate in the development of fully competent oocytes.

  14. Knockdown of connexin43-mediated regulation of the zone of polarizing activity in the developing chick limb leads to digit truncation.

    Science.gov (United States)

    Law, Lee Yong; Lin, Jun Sheng; Becker, David L; Green, Colin R

    2002-12-01

    In the developing chick wing, the use of antisense oligodeoxynucleotides to transiently knock down the expression of the gap junction protein, connexin43 (Cx43), results in limb patterning defects, including deletion of the anterior digits. To understand more about how such defects arise, the effects of transient Cx43 knockdown on the expression patterns of several genes known to play pivotal roles in limb formation were examined. Sonic hedgehog (Shh), which is normally expressed in the zone of polarizing activity (ZPA) and is required to maintain both the ZPA and the apical ectodermal ridge (AER), was found to be downregulated in treated limbs within 30 h. Bone morphogenetic protein-2 (Bmp-2), a gene downstream of Shh, was similarly downregulated. Fibroblast growth factor-8 expression, however, was unaltered 30 h after treatment but was greatly reduced at 48 h post-treatment, when the AER begins to regress. Expressions of Bmp-4 and Muscle segment homeobox-like gene (Msx-1) were not affected at any of the time points examined. Cx43 expression is therefore involved in some, but not all patterning cascades, and appears to play a role in the regulation of ZPA activity.

  15. Connexins in Prostate Cancer Initiation and Progression

    Science.gov (United States)

    2013-11-01

    Connexin43 in the Failing Heart . Circ Res, 106, 1153-1163. 69. Bejiarno,E., Girao,H., Yuste,A., Patel,B., Marques,C., Spray,D., Pereira,P., and...Roth C, Warkany J (1953) An analysis of the syndrome of malformations induced by maternal vitam A deficeincy. Effects of restoriation of vitamin A at...the syndrome of malformations induced by maternal vitamin A deficeincy. Effects of restoriation of vitamin A at varruous times during gestation. Am J

  16. Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy

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    Yuanyuan Xie

    2017-11-01

    Full Text Available Background/Aims: Cardiomyopathy-associated gene 1 (CMYA1 plays an important role in embryonic cardiac development, postnatal cardiac remodeling and myocardial injury repair. Abnormal CMYA1 expression may be involved in cardiac dysplasia and primary cardiomyopathy. Our study aims to establish the relationship between CMYA1 and Left ventricular noncompaction cardiomyopathy (LVNC pathogenesis. Methods: We explored the effects of CMYA1 on connexins (Cx, which contribute to gap junction intercellular communication (GJIC, and the underlying signaling pathway in human normal tissues, LVNC myocardial tissues and HL1 cells by means of western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, co-immunoprecipitation and scrape loading-dye transfer. Results: CMYA1 expression was inversely associated with Cx43 and Cx40 expression, as determined by gap junction PCR array analysis. An increased expression and disordered distribution of CMYA1 at the intercalated discs in LVNC myocardial tissue was also observed. CMYA1 and Cx43 are co-expressed and interact in myocardial cells. CMYA1 expression was positively correlated with p-Cx43 (S368 via the Protein kinase C (PKC signaling pathway in myocardial tissue and HL1 cells. The diffusion distance of Lucifer Yellow in the HL1 cells in which CMYA1 was over-expressed or knocked down was significantly less or more than that of the control group, respectively. Conclusion: Abnormal CMYA1 expression affects the expression and phosphorylation of Cx43 through the PKC signaling pathway, which is involved in the regulation of GJIC. CMYA1 participates in the molecular mechanism of LVNC pathogenesis.

  17. Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

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    Rong-Hui Tu

    2017-11-01

    Full Text Available Background/Aims: Previous studies have shown that heat shock protein 90 (HSP90-mediated mitochondrial import of connexin 43 (Cx43 is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. Methods: Cellular models of hypoxic postconditioning (HPC from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS production was assessed with the peroxide-sensitive fluorescent probe 2′,7′-dichlorofluorescin in diacetate (DCFH-DA. The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA, ROS scavengers superoxide dismutase (SOD and catalase (CAT, and small interfering RNA (siRNA targeting Cx43 and HSP90 were also investigated. Results: HPC significantly reduced hypoxia/reoxygenation (H/R-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA or siRNA targeting

  18. Connexins in the early development of the African clawed frog Xenopus laevis (Amphibia: The role of the connexin43 carboxyl terminal tail in the establishment of the dorso-ventral axis

    Directory of Open Access Journals (Sweden)

    Jaime Cofre

    2007-03-01

    Full Text Available Connexins are a family of related proteins identified in vertebrate forming gap junctions, which mediate cell-to-cell communication in early embryos, with an important role in establishing embryonic asymmetry and ‘communication compartments’. By in situ hybridization, immunocytochemistry, reverse transcriptase PCR (RT-PCR and western blotting we show that a Cx43-like molecule is present in oocytes and embryos of the African clawed frog Xenopus laevis, with specific localization in the animal-vegetal axis. This specific distribution is suggestive for an important role for this protein in the establishment of the dorso-ventral axis. Antisense RNA and antibodies directed against rat carboxyl terminal tail of the Cx43 (CT-Cx43 and injected in 1-cell stage Xenopus embryos, induced pronounced alterations in nervous system development, with a severe ventralization phenotype. Coherently, the overexpression of CT-Cx43 produced a dorsalization of the embryos. In antisense treated embryos, the expression of the beta-catenin gene is eliminated from the Nieuwkoop center, the pattern expression of the Chordin, Xnot and Xbra is modified, with no effect in expression of the Goosecoid gene. In CT-Cx43 mRNA treated embryos the pattern of expression of the beta-catenin, Chordin, Goosecoid, Xnot and engrailed-2 genes is modified. The expression of beta-catenin is increased in the Nieuwkoop center, the expression pattern of Chordin and Goosecoid is expanded to the posterior neural plate and engrailed-2 presents ectopic expression in the ventral region. Taken together our data suggest a role for CT-Cx43 as a maternal determinant with a critical function in the formation of the dorso-ventral axis in Xenopus laevis. The Cx43 may be one of the earliest markers of the dorso-ventral axis in these embryos and could possibly be acting through regionalization of factors responsible for the establishment of this axis.

  19. Cell proliferation and expression of connexins differ in melanotic and amelanotic canine oral melanomas.

    Science.gov (United States)

    Teixeira, Tarso Felipe; Gentile, Luciana Boffoni; da Silva, Tereza Cristina; Mennecier, Gregory; Chaible, Lucas Martins; Cogliati, Bruno; Roman, Marco Antonio Leon; Gioso, Marco Antonio; Dagli, Maria Lucia Zaidan

    2014-03-01

    Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.

  20. The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models.

    Science.gov (United States)

    Schrobback, Karsten; Klein, Travis Jacob; Woodfield, Tim B F

    2015-06-01

    Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular

  1. Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43.

    Science.gov (United States)

    Boogerd, Kees-Jan; Wong, L Y Elaine; Christoffels, Vincent M; Klarenbeek, Meinke; Ruijter, Jan M; Moorman, Antoon F M; Barnett, Phil

    2008-06-01

    T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering protein partners of Tbx2 and Tbx3 will shed light on the mechanisms by which these factors regulate these gene programs. Employing an yeast 2-hybrid screen and subsequent in vitro pull-down experiments we demonstrate that muscle segment homeobox genes Msx1 and Msx2 are able to bind the cardiac T-box proteins Tbx2, Tbx3, and Tbx5. This interaction, as that of the related Nkx2.5 protein, is supported by the T-box and homeodomain alone. Overlapping spatiotemporal expression patterns of Msx1 and Msx2 together with the T-box genes during cardiac development in mouse and chicken underscore the biological significance of this interaction. We demonstrate that Msx proteins together with Tbx2 and Tbx3 suppress Cx43 promoter activity and down regulate Cx43 gene activity in a rat heart-derived cell line. Using chromatin immunoprecipitation analysis we demonstrate that Msx1 can bind the Cx43 promoter at a conserved binding site located in close proximity to a previously defined T-box binding site, and that the activity of Msx proteins on this promoter appears dependent in the presence of Tbx3. Msx1 and Msx2 can function in concert with the T-box proteins to suppress Cx43 and other working myocardial genes.

  2. Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric OxideSummary

    Directory of Open Access Journals (Sweden)

    Isola A.M. Brown

    2016-01-01

    Full Text Available Background & Aims: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R; triggering adenosine triphosphate (ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca2+]i in surrounding enteric glia. We tested the hypothesis that the activation of enteric glia contributes to neuron death during inflammation. Methods: We studied neuroinflammation in vivo using the 2,4-dinitrobenzene sulfonic acid model of colitis and in situ using whole-mount preparations of human and mouse intestine. Transgenic mice with a targeted deletion of glial connexin-43 (Cx43 [GFAP::CreERT2+/−/Cx43f/f] were used to specifically disrupt glial signaling pathways. Mice deficient in inducible nitric oxide (NO synthase (iNOS−/− were used to study NO production. Protein expression and oxidative stress were measured using immunohistochemistry and in situ Ca2+ and NO imaging were used to monitor glial [Ca2+]i and [NO]i. Results: Purinergic activation of enteric glia drove [Ca2+]i responses and enteric neuron death through a Cx43-dependent mechanism. Neurotoxic Cx43 activity, driven by NO production from glial iNOS, was required for neuron death. Glial Cx43 opening liberated ATP and Cx43-dependent ATP release was potentiated by NO. Conclusions: Our results show that the activation of glial cells in the context of neuroinflammation kills enteric neurons. Mediators of inflammation that include ATP and NO activate neurotoxic pathways that converge on glial Cx43 hemichannels. The glial response to inflammatory mediators might contribute to the development of motility disorders. Keywords: Enteric Nervous System, Hemichannels

  3. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

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    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  4. Altered thyroid status affects myocardial expression of connexin-43 and susceptibility of rat heart to malignant arrhythmias that can be partially normalized by red palm oil intake

    Czech Academy of Sciences Publication Activity Database

    Szeiffová Bačová, B.; Vinczenzová, C.; Žurmanová, J.; Kašparová, Dita; Knezl, V.; Egan Beňová, T.; Pavelka, Stanislav; Soukup, Tomáš; Tribulová, N.

    2017-01-01

    Roč. 147, č. 1 (2017), s. 63-73 ISSN 0948-6143 R&D Projects: GA MŠk(CZ) LH15279; GA MŠk(CZ) 7AMB14SK123 Grant - others:AV ČR(CZ) SAV-15-03 Program:Bilaterální spolupráce Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * connexin-43 * PKC * red palm oil Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.553, year: 2016

  5. Connexin mutants and cataracts

    Directory of Open Access Journals (Sweden)

    Eric C Beyer

    2013-04-01

    Full Text Available The lens is a multicellular, but avascular tissue that must stay transparent to allow normal transmission of light and focusing of it on the retina. Damage to lens cells and/or proteins can cause cataracts, opacities that disrupt these processes. The normal survival of the lens is facilitated by an extensive network of gap junctions formed predominantly of connexin46 and connexin50. Mutations of the genes that encode these connexins (GJA3 and GJA8 have been identified and linked to inheritance of cataracts in human families and mouse lines. In vitro expression studies of several of these mutants have shown that they exhibit abnormalities that may lead to disease. Many of the mutants reduce or modify intercellular communication due to channel alterations (including loss of function or altered gating or due to impaired cellular trafficking which reduces the number of gap junction channels within the plasma membrane. However, the abnormalities detected in studies of other mutants suggest that they cause cataracts through other mechanisms including gain of hemichannel function (leading to cell injury and death and formation of cytoplasmic accumulations (that may act as light scattering particles. These observations and the anticipated results of ongoing studies should elucidate the mechanisms of cataract development due to mutations of lens connexins and abnormalities of other lens proteins. They may also contribute to our understanding of the mechanisms of disease due to connexin mutations in other tissues.

  6. Impaired osteogenic differentiation associated with connexin43/microRNA-206 in steroid-induced avascular necrosis of the femoral head.

    Science.gov (United States)

    Liu, Gang; Luo, Gaobin; Bo, Zhandong; Liang, Xiaonan; Huang, Jie; Li, Donghui

    2016-08-01

    Connexin(Cx)43 and microRNA(miR)-206 play an important role in osteogenesis. However, their role in steroid-induced femoral head osteonecrosis (SANFH) is still ambiguous. The present study aimed to establish a rabbit model and investigate osteogenesis in steroid-induced femoral head osteonecrosis occurring via Cx43/miR-206 and the changes of Wnt/β-catenin signal pathway-related proteins. A total of 72 adult New Zealand white rabbits were divided randomly into a model group (Group A) and a control group (Group B) of 36 rabbits each. Group A was injected intravenously with lipopolysaccharide (10μg/kg body weight, once per day). After 48h, three injections of methylprednisolone (MPS; 20mg/kg body weight) were administered intramuscularly at 24-hour intervals. Group B were fed and housed under identical conditions but received saline injections. All animals were sacrificed at two, four, and eight weeks from the first MPS injection. Typical early osteonecrosis symptoms were observed in Group A. The expression of miR-206 in Group A was significantly higher than that of Group B. The mRNA and protein levels of Cx43, β-catenin, runt-related transcription factor 2, and alkaline phosphatase gradually decreased while Dickkopf-1 (Dkk-1) gradually increased in Group A compared with Group B. These findings indicated that Cx43/miR-206 is involved in the pathogenesis of early stage SANFH and may be associate with Wnt/β-catenin signal pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Expression of connexin 37, 40, and 43 mRNA and protein in renal preglomerular arterioles

    DEFF Research Database (Denmark)

    Arensbak, B; Mikkelsen, Hanne Birte; Gustafsson, F

    2001-01-01

    arterioles in frozen sections was evaluated. SMC were isolated from kidneys using an iron oxide sieve method and explant technique. Total RNA from these cultures was tested by RT-PCR analysis for the expression of the three connexins mRNA. Using immunofluorescence we examined whether the expression pattern...

  8. Irradiation-Induced Cardiac Connexin-43 and miR-21 Responses Are Hampered by Treatment with Atorvastatin and Aspirin

    Directory of Open Access Journals (Sweden)

    Csilla Viczenczova

    2018-04-01

    Full Text Available Radiation of the chest during cancer therapy is deleterious to the heart, mostly due to oxidative stress and inflammation related injury. A single sub-lethal dose of irradiation has been shown to result in compensatory up-regulation of the myocardial connexin-43 (Cx43, activation of the protein kinase C (PKC signaling along with the decline of microRNA (miR-1 and an increase of miR-21 levels in the left ventricle (LV. We investigated whether drugs with antioxidant, anti-inflammatory or vasodilating properties, such as aspirin, atorvastatin, and sildenafil, may affect myocardial response in the LV and right ventricle (RV following chest irradiation. Adult, male Wistar rats were subjected to a single sub-lethal dose of chest radiation at 25 Gy and treated with aspirin (3 mg/day, atorvastatin (0.25 mg/day, and sildenafil (0.3 mg/day for six weeks. Cx43, PKCε and PKCδ proteins expression and levels of miR-1 as well as miR-21 were determined in the LV and RV. Results showed that the suppression of miR-1 was associated with an increase of total and phosphorylated forms of Cx43 as well as PKCε expression in the LV while having no effect in the RV post-irradiation as compared to the non-irradiated rats. Treatment with aspirin and atorvastatin prevented an increase in the expression of Cx43 and PKCε without change in the miR-1 levels. Furthermore, treatment with aspirin, atorvastatin, and sildenafil completely prevented an increase of miR-21 in the LV while having partial effect in the RV post irradiation. The increase in pro-apoptotic PKCδ was not affected by any of the used treatment. In conclusion, irradiation and drug-induced changes were less pronounced in the RV as compared to the LV. Treatment with aspirin and atorvastatin interfered with irradiation-induced compensatory changes in myocardial Cx43 protein and miR-21 by preventing their elevation, possibly via amelioration of oxidative stress and inflammation.

  9. 43 CFR 29.6 - Financing, accounting, and audit.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Financing, accounting, and audit. 29.6 Section 29.6 Public Lands: Interior Office of the Secretary of the Interior TRANS-ALASKA PIPELINE LIABILITY FUND § 29.6 Financing, accounting, and audit. (a)(1) The Operator of the Pipeline shall notify...

  10. 43 CFR 29.8 - Notification and advertisement.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Notification and advertisement. 29.8... LIABILITY FUND § 29.8 Notification and advertisement. (a) As soon as the person in charge of a vessel has... advertisement no later than 45 days from the date the Fund receives notice of the incident and shall continue...

  11. Joint diseases: from connexins to gap junctions.

    Science.gov (United States)

    Donahue, Henry J; Qu, Roy W; Genetos, Damian C

    2017-12-19

    Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels, releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions, membrane-spanning channels that facilitate cell-cell communication by enabling signalling molecules of approximately 1 kDa to pass from one cell to an adjacent cell. Connexins are expressed in joint tissues including bone, cartilage, skeletal muscle and the synovium. Indicative of their importance as gap junction components, connexins are also known as gap junction proteins, but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and highlights the therapeutic potential of connexins.

  12. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

    Science.gov (United States)

    Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

    2016-12-01

    We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Conflicting Roles of Connexin43 in Tumor Invasion and Growth in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Miaki Uzu

    2018-04-01

    Full Text Available The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs and hemichannels (HCs which are composed of hexamer of connexin43 (Cx43 protein. In particular, we discuss how GJ intercellular communication (GJIC in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are “hijacked” by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood–brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent on what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, needs to be revisited and understood together with new findings on Cx proteins and HC

  14. Connexins and the kidney

    DEFF Research Database (Denmark)

    Hanner, Fiona; Sørensen, Charlotte Mehlin; Holstein-Rathlou, Niels-Henrik

    2010-01-01

    Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules......, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling....... Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved...

  15. Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Aschner, Michael [Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Luo, Wen-Jing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jing-Yuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2016-04-15

    As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

  16. Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

    International Nuclear Information System (INIS)

    Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua; Aschner, Michael; Luo, Wen-Jing; Chen, Jing-Yuan

    2016-01-01

    As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

  17. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G

    2004-01-01

    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the

  18. Bone morphogenetic protein-2 (BMP-2 and transforming growth factor-β1 (TGF-β1 alter connexin 43 phosphorylation in MC3T3-E1 Cells

    Directory of Open Access Journals (Sweden)

    Rudkin George H

    2001-07-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs and transforming growth factor-βs (TGF-βs are important regulators of bone repair and regeneration. BMP-2 and TGF-β1 have been shown to inhibit gap junctional intercellular communication (GJIC in MC3T3-E1 cells. Connexin 43 (Cx43 has been shown to mediate GJIC in osteoblasts and it is the predominant gap junctional protein expressed in these murine osteoblast-like cells. We examined the expression, phosphorylation, and subcellular localization of Cx43 after treatment with BMP-2 or TGF-β1 to investigate a possible mechanism for the inhibition of GJIC. Results Northern blot analysis revealed no detectable change in the expression of Cx43 mRNA. Western blot analysis demonstrated no significant change in the expression of total Cx43 protein. However, significantly higher ratios of unphosphorylated vs. phosphorylated forms of Cx43 were detected after BMP-2 or TGF-β1 treatment. Immunofluorescence and cell protein fractionation revealed no detectable change in the localization of Cx43 between the cytosol and plasma membrane. Conclusions BMP-2 and TGF-β1 do not alter expression of Cx43 at the mRNA or protein level. BMP-2 and TGF-β1 may inhibit GJIC by decreasing the phosphorylated form of Cx43 in MC3T3-E1 cells.

  19. Susceptibility of rats with altered thyroid status to malignant arrhythmias is primarily related to myocardial levels of connexin-43 and can be partially ameliorated by supplementation with red palm oil

    Czech Academy of Sciences Publication Activity Database

    Bačová, B.; Vinczenzová, C.; Žurmanová, J.; Kašparová, Dita; Knezl, V.; Radošinská, J.; Beňová, T.; Pavelka, Stanislav; Soukup, Tomáš; Tribulová, N.

    2013-01-01

    Roč. 18, Suppl A (2013), 41A-46A ISSN 1205-6626 R&D Projects: GA MŠk(CZ) 7AMB12SK158; GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GAP304/12/0259 Grant - others:Univerzita Karlova(CZ) 628412 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * connexin-43 * PKC.epsilon * red palm oil Subject RIV: ED - Physiology Impact factor: 0.758, year: 2013

  20. Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

    Science.gov (United States)

    Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

    2013-01-01

    Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. PMID:24260576

  1. 29 CFR 4281.43 - Notices of insolvency and annual updates.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Notices of insolvency and annual updates. 4281.43 Section 4281.43 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION INSOLVENCY... MASS WITHDRAWAL Benefit Suspensions § 4281.43 Notices of insolvency and annual updates. (a) Requirement...

  2. Cloning, embryonic expression, and functional characterization of two novel connexins from Xenopus laevis

    NARCIS (Netherlands)

    de Boer, Teun P.; Kok, Bart; Roël, Giulietta; van Veen, Toon A. B.; Destrée, Olivier H. J.; Rook, Martin B.; Vos, Marc A.; de Bakker, Jacques M. T.; van der Heyden, Marcel A. G.

    2006-01-01

    Vertebrate gap junctions are constituted of connexin (Cx) proteins. In Xenopus laevis, only seven different Cxs have been described so far. Here, we identify two new Cxs from X. laevis. Cx28.6 displays > 60% amino acid identity with human Cx25, Cx29 displays strong homology with mouse Cx26 and Cx30.

  3. Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

    Science.gov (United States)

    Alaga, Katanya C; Crawford, Melissa; Dagnino, Lina; Laird, Dale W

    2017-01-01

    At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

  4. Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

    Science.gov (United States)

    Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

    2016-02-01

    Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of

  5. Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

    International Nuclear Information System (INIS)

    Ganesan, Shanthi; Nteeba, Jackson; Keating, Aileen F.

    2015-01-01

    The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility

  6. Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-01-01

    The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility.

  7. Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with erythrokeratodermia variabilis

    DEFF Research Database (Denmark)

    Plantard, Laure; Huber, Marcel; Macari, Francoise

    2003-01-01

    Connexins are homologous four-transmembrane-domain proteins and major components of gap junctions. We recently identified mutations in either GJB3 or GJB4 genes, encoding respectively connexin 31 (Cx31) or 30.3 (Cx30.3), as causally involved in erythrokeratodermia variabilis (EKV), a mostly autos...

  8. Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS.

    Science.gov (United States)

    Bisht, Rohit; Mandal, Abhirup; Rupenthal, Ilva D; Mitra, Ashim K

    2016-12-01

    This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r 2  = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 μg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 μg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection.

  9. A simple RT-PCR-based strategy for screening connexin identity

    Directory of Open Access Journals (Sweden)

    M. Urban

    1999-08-01

    Full Text Available Vertebrate gap junctions are aggregates of transmembrane channels which are composed of connexin (Cx proteins encoded by at least fourteen distinct genes in mammals. Since the same Cx type can be expressed in different tissues and more than one Cx type can be expressed by the same cell, the thorough identification of which connexin is in which cell type and how connexin expression changes after experimental manipulation has become quite laborious. Here we describe an efficient, rapid and simple method by which connexin type(s can be identified in mammalian tissue and cultured cells using endonuclease cleavage of RT-PCR products generated from "multi primers" (sense primer, degenerate oligonucleotide corresponding to a region of the first extracellular domain; antisense primer, degenerate oligonucleotide complementary to the second extracellular domain that amplify the cytoplasmic loop regions of all known connexins except Cx36. In addition, we provide sequence information on RT-PCR primers used in our laboratory to screen individual connexins and predictions of extension of the "multi primer" method to several human connexins.

  10. Connexins and pannexins in the integumentary system: the skin and appendages.

    Science.gov (United States)

    Faniku, Chrysovalantou; Wright, Catherine S; Martin, Patricia E

    2015-08-01

    The integumentary system comprises the skin and its appendages, which includes hair, nails, feathers, sebaceous and eccrine glands. In this review, we focus on the expression profile of connexins and pannexins throughout the integumentary system in mammals, birds and fish. We provide a picture of the complexity of the connexin/pannexin network illustrating functional importance of these proteins in maintaining the integrity of the epidermal barrier. The differential regulation and expression of connexins and pannexins during skin renewal, together with a number of epidermal, hair and nail abnormalities associated with mutations in connexins, emphasize that the correct balance of connexin and pannexin expression is critical for maintenance of the skin and its appendages with both channel and non-channel functions playing profound roles. Changes in connexin expression during both hair and feather regeneration provide suggestions of specialized communication compartments. Finally, we discuss the potential use of zebrafish as a model for connexin skin biology, where evidence mounts that differential connexin expression is involved in skin patterning and pigmentation.

  11. Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via activation of the p38 and c-Fos/AP-1 signalling pathway.

    Science.gov (United States)

    Morioka, N; Suekama, K; Zhang, F F; Kajitani, N; Hisaoka-Nakashima, K; Takebayashi, M; Nakata, Y

    2014-06-01

    Intercellular communication via gap junctions, comprised of connexin (Cx) proteins, allow for communication between astrocytes, which in turn is crucial for maintaining CNS homeostasis. The expression of Cx43 is decreased in post-mortem brains from patients with major depression. A potentially novel mechanism of tricyclic antidepressants is to increase the expression and functioning of gap junctions in astrocytes. The effect of amitriptyline on the expression of Cx43 and gap junction intercellular communication (GJIC) in rat primary cultured cortical astrocytes was investigated. We also investigated the role of p38 MAPK intracellular signalling pathway in the amitriptyline-induced expression of Cx43 and GJIC. Treatment with amitriptyline for 48 h significantly up-regulated Cx43 mRNA, protein and GJIC. The up-regulation of Cx43 was not monoamine-related since noradrenaline, 5-HT and dopamine did not induce Cx43 expression and pretreatment with α- and β-adrenoceptor antagonists had no effect. Intracellular signalling involved p38 MAPK, as amitriptyline significantly increased p38 MAPK phosphorylation and Cx43 expression and GJIC were significantly blocked by the p38 inhibitor SB 202190. Furthermore, amitriptyline-induced Cx43 expression and GJIC were markedly reduced by transcription factor AP-1 inhibitors (curcumin and tanshinone IIA). The translocation of c-Fos from the cytosol and the nucleus of cortical astrocytes was increased by amitriptyline, and this response was dependent on p38 activity. These findings indicate a novel mechanism of action of amitriptyline through cortical astrocytes, and further suggest that targeting this mechanism could lead to the development of a new class of antidepressants. © 2014 The British Pharmacological Society.

  12. 29 CFR 783.43 - Computation of seaman's minimum wage.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Computation of seaman's minimum wage. 783.43 Section 783.43...'s minimum wage. Section 6(b) requires, under paragraph (2) of the subsection, that an employee...'s minimum wage requirements by reason of the 1961 Amendments (see §§ 783.23 and 783.26). Although...

  13. THE FEATURES OF CONNEXINS EXPRESSION IN THE CELLS OF NEUROVASCLAR UNIT IN NORMAL CONDITIONS AND HYPOXIA IN VITRO

    Directory of Open Access Journals (Sweden)

    A. V. Morgun

    2014-01-01

    Full Text Available The aim of this research was to assess a role of connexin 43 (Cx43 and associated molecule CD38 in the regulation of cell-cell interactions in the neurovascular unit (NVU in vitro in physiological conditions and in hypoxia.Materials and methods. The study was done using the original neurovascular unit model in vitro. The NVU consisted of three cell types: neurons, astrocytes, and cerebral endothelial cells derived from rats. Hypoxia was induced by incubating cells with sodium iodoacetate for 30 min at37 °C in standard culture conditions.Results. We investigated the role of connexin 43 in the regulation of cell interactions within the NVU in normal and hypoxic injury in vitro. We found that astrocytes were characterized by high levels of expression of Cx43 and low level of CD38 expression, neurons demonstrated high levels of CD38 and low levels of Cx43. In hypoxic conditions, the expression of Cx43 and CD38 in astrocytes markedly increased while CD38 expression in neurons decreased, however no changes were found in endothelial cells. Suppression of Cx43 activity resulted in down-regulation of CD38 in NVU cells, both in physiological conditions and at chemical hypoxia.Conclusion. Thus, the Cx-regulated intercellular NAD+-dependent communication and secretory phenotype of astroglial cells that are the part of the blood-brain barrier is markedly changed in hypoxia.

  14. Connexins, diabetes and the metabolic syndrome.

    Science.gov (United States)

    Hamelin, Romain; Allagnat, Florent; Haefliger, Jacques-Antoine; Meda, Paolo

    2009-02-01

    Diabetes and the related metabolic syndrome are multi system disorders that result from improper interactions between various cell types. Even though the underlying mechanism remains to be fully understood, it is most likely that both the long and the short distance range cell interactions, which normally ensure the physiologic functioning of the pancreas, and its relationships with the insulin-targeted organs, are altered. This review focuses on the short-range type of interactions that depend on the contact between adjacent cells and, specifically, on the interactions that are dependent on connexins. The widespread distribution of these membrane proteins, their multiple modes of action, and their interactions with conditions/molecules associated to both the pathogenesis and the treatment of the 2 main forms of diabetes and the metabolic syndrome, make connexins an essential part of the chain of events that leads to metabolic diseases. Here, we review the present state of knowledge about the molecular and cell biology of the connexin genes and proteins, their general mechanisms of action, the roles specific connexin species play in the endocrine pancreas and the major insulin-targeted organs, under physiological and patho-physiological conditions.

  15. 29 CFR 34.43 - Complaints and investigations.

    Science.gov (United States)

    2010-07-01

    ... Equal Pay Act of 1963, as amended (29 U.S.C. 206(d)), or the Age Discrimination in Employment Act of... Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY REQUIREMENTS OF THE JOB TRAINING PARTNERSHIP ACT OF 1982, AS AMENDED (JTPA) Compliance Procedures § 34.43...

  16. Disruption in connexin-based communication is associated with intracellular Ca²⁺ signal alterations in astrocytes from Niemann-Pick type C mice.

    Directory of Open Access Journals (Sweden)

    Pablo J Sáez

    Full Text Available Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1⁻/⁻ showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1⁻/⁻ hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1⁻/⁻ astrocytes also showed more intracellular Ca²⁺ signal oscillations mediated by functional connexin 43 hemichannels and P2Y₁ receptors. Therefore, Npc1⁻/⁻ astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease.

  17. Disruption in connexin-based communication is associated with intracellular Ca²⁺ signal alterations in astrocytes from Niemann-Pick type C mice.

    Science.gov (United States)

    Sáez, Pablo J; Orellana, Juan A; Vega-Riveros, Natalia; Figueroa, Vania A; Hernández, Diego E; Castro, Juan F; Klein, Andrés D; Jiang, Jean X; Zanlungo, Silvana; Sáez, Juan C

    2013-01-01

    Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1⁻/⁻) showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1⁻/⁻ hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1⁻/⁻ astrocytes also showed more intracellular Ca²⁺ signal oscillations mediated by functional connexin 43 hemichannels and P2Y₁ receptors. Therefore, Npc1⁻/⁻ astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease.

  18. Adenovirus Vector E4 Gene Regulates Connexin 40 and 43 Expression in Endothelial Cells via PKA and PI3K Signal Pathways

    Science.gov (United States)

    Zhang, Fan; Cheng, Joseph; Lam, George; Jin, David K.; Vincent, Loïc; Hackett, Neil R.; Wang, Shiyang; Young, Lauren M.; Hempstead, Barbara; Crystal, Ronald G.; Rafii, Shahin

    2010-01-01

    Connexins (Cxs) provide a means for intercellular communication and play important roles in the pathophysiology of vascular cardiac diseases. Infection of endothelial cells (ECs) with first-generation E1/E3-deleted E4+ adenovirus (AdE4+) selectively modulates the survival and angiogenic potential of ECs by as of yet unrecognized mechanisms. We show here that AdE4+ vectors potentiate Cx expression in ECs in vitro and in mouse heart tissue. Infection of ECs with AdE4+, but not AdE4−, resulted in a time- and dose-dependent induction of junctional Cx40 expression and suppression of Cx43 protein and mRNA expression. Treatment of ECs with PKA inhibitor H89 or PI3K inhibitor LY294002 prevented the AdE4+-mediated regulation of Cx40 and Cx43 that was associated with diminished AdE4+-mediated survival of ECs. Moreover, both PKA activity and cAMP-response element (CRE)-binding activity were enhanced by treatment of ECs with AdE4+. However, there is no causal evidence of a cross-talk between the 2 modulatory pathways, PKA and PI3K. Remarkably, Cx40 immunostaining was markedly increased and Cx43 was decreased in the heart tissue of mice treated with intratracheal AdE4+. Taken together, these results suggest that AdE4+ may play an important role in the regulation of Cx expression in ECs, and that these effects are mediated by both the PKA/CREB and PI3K signaling pathways. PMID:15831817

  19. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury

    DEFF Research Database (Denmark)

    Lee, I. Hui; Lindqvist, Eva; Kiehn, Ole

    2005-01-01

    Spinal cord injury induces a complex cascade of degenerative and remodeling events evolving over time. The possible roles of changed intercellular communication via gap junctions after spinal cord injury (SCI) have remained relatively unexplored. We investigated the temporospatial expression...... patterns of gap junctional genes and proteins, connexin 43 (Cx43), Cx36, and Cx32, by in situ hybridization and immunohistochemistry in the rat neonatal, adult normal, and adult injured spinal cord. Cx36 was strongly expressed in immature neurons, and levels declined markedly during development, whereas Cx...

  20. 29 CFR 801.43 - Civil money penalties-payment and collection.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Civil money penalties-payment and collection. 801.43... OTHER LAWS APPLICATION OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 Enforcement § 801.43 Civil money... by certified check or by money order, made payable to the order of “Wage and Hour Division, Labor...

  1. Connexin-based intercellular communication and astrocyte heterogeneity.

    Science.gov (United States)

    Theis, Martin; Giaume, Christian

    2012-12-03

    This review gives an overview of the current knowledge on connexin-mediated communication in astrocytes, covering gap junction and hemichannel functions mediated by connexins. Astroglia is the main brain cell type that expresses the largest amount of connexin and exhibits high level of gap junctional communication compared to neurons and oligodendrocytes. However, in certain developmental and regional situations, astrocytes are also coupled with oligodendrocytes and neurons. This heterotypic coupling is infrequent and minor in terms of extent of the coupling area, which does not mean that it is not important in terms of cell interaction. Here, we present an update on heterogeneity of connexin expression and function at the molecular, subcellular, cellular and networking levels. Interestingly, while astrocytes were initially considered as a homogenous population, there is now increasing evidence for morphological, developmental, molecular and physiological heterogeneity of astrocytes. Consequently, the specificity of gap junction channel- and hemichannel-mediated communication, which tends to synchronize cell populations, is also a parameter to take into account when neuroglial interactions are investigated. This article is part of a Special Issue entitled Electrical Synapses. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain

    Directory of Open Access Journals (Sweden)

    Ribeiro Ana C

    2009-04-01

    Full Text Available Abstract Background Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36. Results Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH, and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36. Conclusion Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.

  3. Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

    Science.gov (United States)

    García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.

    2015-01-01

    Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422

  4. Genomic instability induced in distant progeny of bystander cells depends on the connexins expressed in the irradiated cells.

    Science.gov (United States)

    de Toledo, Sonia M; Buonanno, Manuela; Harris, Andrew L; Azzam, Edouard I

    2017-10-01

    To examine the time window during which intercellular signaling though gap junctions mediates non-targeted (bystander) effects induced by moderate doses of ionizing radiation; and to investigate the impact of gap junction communication on genomic instability in distant progeny of bystander cells. A layered cell culture system was developed to investigate the propagation of harmful effects from irradiated normal or tumor cells that express specific connexins to contiguous bystander normal human fibroblasts. Irradiated cells were exposed to moderate mean absorbed doses from 3.7 MeV α particle, 1000 MeV/u iron ions, 600 MeV/u silicon ions, or 137 Cs γ rays. Following 5 h of co-culture, pure populations of bystander cells, unexposed to secondary radiation, were isolated and DNA damage and oxidative stress was assessed in them and in their distant progeny (20-25 population doublings). Increased frequency of micronucleus formation and enhanced oxidative changes were observed in bystander cells co-cultured with confluent cells exposed to either sparsely ionizing ( 137 Cs γ rays) or densely ionizing (α particles, energetic iron or silicon ions) radiations. The irradiated cells propagated signals leading to biological changes in bystander cells within 1 h of irradiation, and the effect required cellular coupling by gap junctions. Notably, the distant progeny of isolated bystander cells also exhibited increased levels of spontaneous micronuclei. This effect was dependent on the type of junctional channels that coupled the irradiated donor cells with the bystander cells. Previous work showed that gap junctions composed of connexin26 (Cx26) or connexin43 (Cx43) mediate toxic bystander effects within 5 h of co-culture, whereas gap junctions composed of connexin32 (Cx32) mediate protective effects. In contrast, the long-term progeny of bystander cells expressing Cx26 or Cx43 did not display elevated DNA damage, whereas those coupled by Cx32 had enhanced DNA

  5. Intercellular communications within the rat anterior pituitary. XVI: postnatal changes of distribution of S-100 protein positive cells, connexin 43 and LH-RH positive sites in the pars tuberalis of the rat pituitary gland. An immunohistochemical and electron microscopic study.

    Science.gov (United States)

    Wada, Ikuo; Sakuma, Eisuke; Shirasawa, Nobuyuki; Wakabayashi, Kenjiro; Otsuka, Takanobu; Hattori, Kazuki; Yashiro, Takashi; Herbert, Damon C; Soji, Tsuyoshi

    2014-02-01

    The architecture of luteinizing hormone-releasing hormone (LH-RH) nerve ends and the S-100 protein containing folliculo-stellate cells forming gap junctions in the pars tuberalis is basically important in understanding the regulation of the hormone producing mechanism of anterior pituitary glands. In this study, intact male rats 5-60 days old were prepared for immunohistochemistry and electron microscopy. From immunostained sections, the S-100 containing cells in pars tuberalis were first detected on day 30 and increased in number to day 60; this was parallel to the immunohistochemical staining of gap junction protein, connexin 43. LH-RH positive sites were clearly observed on just behind the optic chiasm and on the root of pituitary stalk on day 30. On day 60, the width of layer increased, while follicles and gap junctions were frequently observed between agranular cells in 10 or more layers of pars tuberalis. In the present study, we investigated the sexual maturation of the anterior pituitary glands through the postnatal development of S-100 positive cells, connexin 43 and LH-RH nerves. It is suggested that the folliculo-stellate cell system including the LH-RH neurons in the pars tuberalis participates in the control of LH secretion along with the portal vein system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Connexin: a potential novel target for protecting the central nervous system?

    Directory of Open Access Journals (Sweden)

    Hong-yan Xie

    2015-01-01

    Full Text Available Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

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

    Science.gov (United States)

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

    2003-01-01

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

  8. Moving from Evaluation to Trial: How do SMEs Start Adopting Cloud ERP?

    Directory of Open Access Journals (Sweden)

    Siti Aisyah Salim

    2015-10-01

    Full Text Available The advent of cloud technology involving low subscription overheads cost has provided small and medium-sized enterprises (SMEs with the opportunity to adopt new cloud-based corporate-wide systems (i.e., cloud ERP. This technology, operating through subscription-based services, has now provided SMEs with a complete range of IT applications that were once restricted to larger organisations. As anecdotal evidences suggest, SMEs are increasingly adopting cloud-based ERP software. The selection of an ERP is a complex process involving multiple stages and stakeholders, suggesting the importance of closer examination of cloud ERP adoption in SMEs. Yet, prior studies have predominantly treated technology adoption as a single activity and largely ignored the issue of ERP adoption in SMEs. Understanding of the process nature of the adoption and the factors that are important in each stage of the adoption potentially may result in guiding SMEs to make well-informed decisions throughout the ERP selection process. Thus, our study proposes that the adoption of cloud ERP should be examined as a multi-stage process. Using the Theory of Planned Behaviour (TPB and Ettlie’s adoption stages, as well as employing data gathered from 162 owners of SMEs, our findings show that the factors that influence the intention to adopt cloud ERP vary significantly across adoptive stages.

  9. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes.

    Science.gov (United States)

    Dere, E; De Souza-Silva, M A; Frisch, C; Teubner, B; Söhl, G; Willecke, K; Huston, J P

    2003-08-01

    Gap-junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell-type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap-junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30-/-, Cx30+/-, and Cx30+/+ mice in the open-field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30-/- mice showed reduced exploratory activity in terms of rearings but not locomotion in the open-field and object exploration task. Furthermore, Cx30-/- mice exhibited anxiogenic behaviour as shown by higher open-field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30-/- mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/- mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5-hydroxyindole acid (5-HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/- mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap-junctional signalling in behavioural processes.

  10. ERP=Efficiency

    Science.gov (United States)

    Violino, Bob

    2008-01-01

    This article discusses the enterprise resource planning (ERP) system. Deploying an ERP system is one of the most extensive--and expensive--IT projects a college or university can undertake. The potential benefits of ERP are significant: a more smoothly running operation with efficiencies in virtually every area of administration, from automated…

  11. Impact of Genetic Counseling and Connexin-26 and Connexin-30 Testing on Deaf Identity and Comprehension of Genetic Test Results in a Sample of Deaf Adults: A Prospective, Longitudinal Study

    Science.gov (United States)

    Palmer, Christina G. S.; Boudreault, Patrick; Baldwin, Erin E.; Sinsheimer, Janet S.

    2014-01-01

    Using a prospective, longitudinal study design, this paper addresses the impact of genetic counseling and testing for deafness on deaf adults and the Deaf community. This study specifically evaluated the effect of genetic counseling and Connexin-26 and Connexin-30 genetic test results on participants' deaf identity and understanding of their genetic test results. Connexin-26 and Connexin-30 genetic testing was offered to participants in the context of linguistically and culturally appropriate genetic counseling. Questionnaire data collected from 209 deaf adults at four time points (baseline, immediately following pre-test genetic counseling, 1-month following genetic test result disclosure, and 6-months after result disclosure) were analyzed. Four deaf identity orientations (hearing, marginal, immersion, bicultural) were evaluated using subscales of the Deaf Identity Development Scale-Revised. We found evidence that participants understood their specific genetic test results following genetic counseling, but found no evidence of change in deaf identity based on genetic counseling or their genetic test results. This study demonstrated that culturally and linguistically appropriate genetic counseling can improve deaf clients' understanding of genetic test results, and the formation of deaf identity was not directly related to genetic counseling or Connexin-26 and Connexin-30 genetic test results. PMID:25375116

  12. Connexin-Dependent Neuroglial Networking as a New Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Mathieu Charvériat

    2017-06-01

    Full Text Available Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the “tripartite synapse” with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial

  13. Connexin-Dependent Neuroglial Networking as a New Therapeutic Target.

    Science.gov (United States)

    Charvériat, Mathieu; Naus, Christian C; Leybaert, Luc; Sáez, Juan C; Giaume, Christian

    2017-01-01

    Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial networking may emerge as

  14. Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.

    Science.gov (United States)

    Nelles, E; Bützler, C; Jung, D; Temme, A; Gabriel, H D; Dahl, U; Traub, O; Stümpel, F; Jungermann, K; Zielasek, J; Toyka, K V; Dermietzel, R; Willecke, K

    1996-09-03

    The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average approximately 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mobilization from glycogen stores, when compared with wild-type liver. Thus, connexin32-containing gap junctions are essential in mouse liver for maximal intercellular propagation of the noradrenaline signal from the periportal (upstream) area, where it is received from sympathetic nerve endings, to perivenous (downstream) hepatocytes. In connexin32-defective liver, the amount of connexin26 protein expressed was found to be lower than in wild-type liver, and the total area of gap junction plaques was approximately 1000-fold smaller than in wild-type liver. In contrast to patients with connexin32 defects suffering from X chromosome-linked Charcot-Marie-Tooth disease (CMTX) due to demyelination in Schwann cells of peripheral nerves, connexin32-deficient mice did not show neurological abnormalities when analyzed at 3 months of age. It is possible, however, that they may develop neurodegenerative symptoms at older age.

  15. Role of Connexin40 in the autoregulatory response of the afferent arteriole

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Giese, Isaiah; Braunstein, Thomas Hartig

    2012-01-01

    Connexins in renal arterioles affect autoregulation of arteriolar tonus and renal blood flow and are believed to be involved in the transmission of the tubuloglomerular feedback (TGF) response across the cells of the juxtaglomerular apparatus. Connexin40 (Cx40) also plays a significant role in th...

  16. Teaching ERP Systems: A Multi-Perspective View on the ERP System Market

    Science.gov (United States)

    Winkelmann, Axel; Leyh, Christian

    2010-01-01

    In order to increase the diversity in IS education, we discuss an approach for teaching medium-sized ERP systems in university courses. Many of today's IS curricula are biased toward a few large ERP packages. Nevertheless, these ERP systems are only a part of the ERP market. Therefore, this paper describes a course outline for an additional course…

  17. Evolution of ERP systems

    NARCIS (Netherlands)

    Wortmann, J.C.; Bititci, U.S.; Carrie, A.S.

    1998-01-01

    This paper describes the development of ERP systems over time. It explores both the functionality and the technology of ERP-systems. It explains the increased importance of ERP systems in practice. The paper also addresses the difficulties encountered in implementing ERP systems in real life. Modern

  18. Intrinsic Factors for Continued ERP Learning: A Precursor to Interdisciplinary ERP Curriculum Design

    Science.gov (United States)

    Chen, Kuanchin; Razi, Muhammad; Rienzo, Thomas

    2011-01-01

    Unilateral enterprise resource planning (ERP) curriculum improvements from the instructor's perspective are likely to generate only limited success. Understanding student motivations and beliefs with ERP systems is the missing link to effective ERP education. Relatively little attention in the ERP literature has been given to student learning…

  19. Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice.

    OpenAIRE

    Nelles, E; Bützler, C; Jung, D; Temme, A; Gabriel, H D; Dahl, U; Traub, O; Stümpel, F; Jungermann, K; Zielasek, J; Toyka, K V; Dermietzel, R; Willecke, K

    1996-01-01

    The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average approximately 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mob...

  20. Hands-On ERP Learning: Using OpenERP[R], an Alternative to SAP[R

    Science.gov (United States)

    Ayyagari, Ramakrishna

    2011-01-01

    Recent struggles with ERP systems (Kanaracus, 2010) highlight that teaching ERP skills is still very relevant today. Previous research suggests that knowledge of ERP concepts is more important than skills with any particular ERP package (Strong et al., 2006). However, a review of published studies in "JISE" shows a bias towards commercial ERP…

  1. Phylogenetic and bioinformatic analysis of gap junction-related proteins, innexins, pannexins and connexins.

    Science.gov (United States)

    Fushiki, Daisuke; Hamada, Yasuo; Yoshimura, Ryoichi; Endo, Yasuhisa

    2010-04-01

    All multi-cellular animals, including hydra, insects and vertebrates, develop gap junctions, which communicate directly with neighboring cells. Gap junctions consist of protein families called connexins in vertebrates and innexins in invertebrates. Connexins and innexins have no homology in their amino acid sequence, but both are thought to have some similar characteristics, such as a tetra-membrane-spanning structure, formation of a channel by hexamer, and transmission of small molecules (e.g. ions) to neighboring cells. Pannexins were recently identified as a homolog of innexins in vertebrate genomes. Although pannexins are thought to share the function of intercellular communication with connexins and innexins, there is little information about the relationship among these three protein families of gap junctions. We phylgenetically and bioinformatically examined these protein families and other tetra-membrane-spanning proteins using a database and three analytical softwares. The clades formed by pannexin families do not belong to the species classification but do to paralogs of each member of pannexins. Amino acid sequences of pannexins are closely related to those of innexins but less to those of connexins. These data suggest that innexins and pannexins have a common origin, but the relationship between innexins/pannexins and connexins is as slight as that of other tetra-membrane-spanning members.

  2. TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

    Science.gov (United States)

    Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

    2009-02-01

    Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

  3. Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia burgdorferi reveal the reason for different affinities for complement regulator factor H.

    Science.gov (United States)

    Brangulis, Kalvis; Petrovskis, Ivars; Kazaks, Andris; Akopjana, Inara; Tars, Kaspars

    2015-05-01

    Borrelia burgdorferi is the causative agent of Lyme disease, which can be acquired after the bite of an infected Ixodes tick. As a strategy to resist the innate immunity and to successfully spread and proliferate, B. burgdorferi expresses a set of outer membrane proteins that are capable of binding complement regulator factor H (CFH), factor H-like protein 1 (CFHL-1) and factor H-related proteins (CFHR) to avoid complement-mediated killing. B. burgdorferi B31 contains three proteins that belong to the Erp (OspE/F-related) protein family and are capable of binding CFH and some CFHRs, namely ErpA, ErpC and ErpP. We have determined the crystal structure of ErpP at 2.53Å resolution and the crystal structure of ErpC at 2.15Å resolution. Recently, the crystal structure of the Erp family member OspE from B. burgdorferi N40 was determined in complex with CFH domains 19-20, revealing the residues involved in the complex formation. Despite the high sequence conservation between ErpA, ErpC, ErpP and the homologous protein OspE (78-80%), the affinity for CFH and CFHRs differs markedly among the Erp family members, suggesting that ErpC may bind only CFHRs but not CFH. A comparison of the binding site in OspE with those of ErpC and ErpP revealed that the extended loop region, which is only observed in the potential binding site of ErpC, plays an important role by preventing the binding of CFH. These results can explain the inability of ErpC to bind CFH, whereas ErpP and ErpA still possess the ability to bind CFH. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Um estudo sobre a implantação de sistemas ERP: pesquisa realizada em grandes empresas industriais A study on ERP system implementation: a survey at large industrial companies

    Directory of Open Access Journals (Sweden)

    Lindomar Subtil de Oliveira

    2012-08-01

    Full Text Available A notável expansão dos sistemas ERP gerou muitas discussões entre especialistas, pesquisadores e empresários, no intuito de encontrar uma explicação para os diversos casos de sucesso e insucesso na sua implantação. O objetivo desse estudo empírico foi identificar nas 50 maiores empresas industriais atuantes no Brasil quais os principais fatores que dificultam ou contribuem para o processo de implantação de sistemas ERP. Tratou-se de uma pesquisa aplicada e exploratória. Além do levantamento bibliográfico, elaborou-se um questionário estruturado com 29 perguntas, o qual foi respondido pelos gestores de TI (tecnologia de informação das empresas selecionadas. Os resultados demonstraram que fatores relacionados às dificuldades funcionais do sistema, customização, adaptação aos processos de negócio e carências do ERP no apoio aos planos estratégicos globais foram alguns dos pontos considerados mais complexos. Essencialmente, outros fatores concernentes ao intenso treinamento, engajamento das principais lideranças, fatores humanos, sociais e culturais também foram referidos.The large utilization of ERP systems has become the scope of discussion among specialists, researchers and professionals of the area, with the purpose of finding an answer for the success and failure cases on ERP implementation. This paper aimed to present an experimental study with the 50 biggest industrial companies with activities in Brazil in order to identify the main factors that contribute or hinder ERP implementation processes. This study was characterized by an applied and exploratory research. Besides the bibliographical survey, a structured questionnaire containing 29 questions was elaborated by the researchers and then responded by the IT (Information Technology managers of the selected companies. Results showed that the factors concerning system functionality difficulties, customization, adjustment to business processes, and lack of support

  5. Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep

    OpenAIRE

    Davidson, Joanne O.; Drury, Paul P.; Green, Colin R.; Nicholson, Louise F.; Bennet, Laura; Gunn, Alistair J.

    2014-01-01

    Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103-104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min...

  6. Pemodelan ERP pada Perusahaan Manufaktur dengan Software OpenERP7.0

    Directory of Open Access Journals (Sweden)

    Dewa Komang Mahardika

    2016-01-01

    Full Text Available Pemodelan dan penerapan sistem informasi terintegrasi dalam proses bisnis perlu dilakukan untuk peningkatan kinerja dan kepuasan pelanggan. Kinerja yang baik diperoleh jika departemen-departemen di dalamnya sudah terintegrasi dengan baik pula. Enterprise resource planning adalah sistem informasi terintegrasi yang menjadikan sebuah bisnis proses menjadi satu kesatuan sistem. Penelitian yang dilakukan adalah tentang pemodelan ERP pada perusahaan garmen yaitu pada bagian accounting, human resource, dan point of sale dengan software OpenERP. Proses bisnis yang sedang berlangsung pada masing-masing departemen dimodelkan dalam diagram alir. Pemodelan sistem yang baru dihasilkan dari perbaikan terhadap kekurangan model sistem yang lama. Hasil pemodelan yang baru diimplementasikan dalam aplikasi ERP yaitu OpenERP. Sistem terintegrasi dengan bisnis proses yang lebih terencana, terintegrasi dan lebih otomatis dihasilkan dari pemodelan dan implementasi yang dilakukan terhadap sistem yang lama.   Kata Kunci: Enterprise resource planning, Implementasi Bisnis Proses, Pemodelan ERP

  7. Connexins and pannexins: New insights into microglial functions and dysfunctions

    Directory of Open Access Journals (Sweden)

    Rosario Gajardo-Gómez

    2016-09-01

    Full Text Available In a physiological context, microglia adopt a resting phenotype that is associated with the production of anti-inflammatory and neurotrophic factors. In response to a wide variety of insults, they shift to the activated phenotype that is necessary for the proper restoration of brain homeostasis. When the intensity of the threat is relatively high, microglial activation can worsen the damage progression instead of providing protection, with potentially significant consequences for neuronal survival. Coordinated interactions among microglia and with other brain cells, including astrocytes and neurons, is critical for the development of timely and optimal inflammatory responses in the brain parenchyma. Tissue synchronization is in part mediated by connexins and pannexins, which are protein families that form different plasma membrane channels to communicate with neighboring cells. At one end, the gap junction channels (which are exclusively formed by connexins in vertebrates connect the cytoplasm of contacting cells to coordinate electrical and metabolic coupling. At the other end, hemichannels and pannexons (which are formed by connexins and pannexins, respectively communicate via intra- and extracellular compartments and serve as diffusion pathways for the exchange of ions and small molecules. In this review, we discuss the evidence available concerning the functional expression and regulation of connexin- and pannexin-based channels in microglia and their contribution to microglial function and dysfunction. We focus on the possible implications of these channels in microglia-to-microglia, microglia-to-astrocyte and neuron-to-microglia interactions in the inflamed brain.

  8. 29 CFR 1602.43 - Commission's remedy for school systems' or districts' failure to file report.

    Science.gov (United States)

    2010-07-01

    ...' failure to file report. Any school system or district failing or refusing to file report EEO-5 when... 29 Labor 4 2010-07-01 2010-07-01 false Commission's remedy for school systems' or districts' failure to file report. 1602.43 Section 1602.43 Labor Regulations Relating to Labor (Continued) EQUAL...

  9. Inverse relationship between tumour proliferation markers and connexin expression in a malignant cardiac tumour originating from mesenchymal stem cell engineered tissue in a rat in-vivo model.

    Directory of Open Access Journals (Sweden)

    Cathleen eSpath

    2013-04-01

    Full Text Available Background: Recently, we demonstrated the beneficial effects of engineered heart tissues for the treatment of dilated cardiomyopathy in rats. For further development of this technique we started to produce engineered tissue (ET from mesenchymal stem cells. Interestingly, we observed a malignant tumour invading the heart with an inverse relationship between proliferation markers and connexin-expression.Methods: Commercial CD54+/CD90+/CD34-/CD45- bone marrow derived mesenchymal rat stem cells (cBM-MSC, characterized were used for production of mesenchymal stem-cell-ET (MSC-ET by suspending them in a collagen-I, matrigel-mixture and cultivating for 14 days with electrical stimulation. 3 MSC-ET were implanted around the beating heart of adult rats for days. Another 3 MSC-ET were produced from freshly isolated rat bone marrow derived stem cells (sBM-MSC.Results: 3 weeks after implantation of the MSC-ETs the hearts were surgically excised. While in 5/6 cases the ET was clearly distinguishable and was found as a ring containing mostly connective tissue around the heart, in 1/6 the heart was completely surrounded by a huge, undifferentiated, pleomorphic tumour originating from the cMSC-ET (cBM-MSC, classified as a high grade malignant sarcoma. Quantitatively we found a clear inverse relationship between cardiac connexin-expression (Cx43, Cx40 or Cx45 and increased Ki-67 expression (Cx43: p<0.0001, Cx45: p<0.03, Cx40: p<0.014. At the tumour-heart border there were significantly more Ki-67 positive cells (p=0.001, and only 2% Cx45 and Ki-67-expressing cells, while the other connexins were nearly completely absent (p<0.0001.Conclusions and hypothesis: These observations strongly suggest the hypothesis, that invasive tumour growth is accompanied by reduction in connexins. This implicates that gap junction communication between tumour and normal tissue is reduced or absent, which could mean that growth and differentiation signals can not be exchanged.

  10. Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

    Science.gov (United States)

    Johnson, Robert D; Camelliti, Patrizia

    2018-03-15

    The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

  11. Working with OpenERP

    CERN Document Server

    Moss, Greg

    2013-01-01

    This book is a practical, hands-on guide that provides the reader with a number of real-world examples and step-by-step instructions.""Working with OpenERP"" is written to make it easy for even a non-technical business person to begin implementing OpenERP in their business. This book uses real-world examples and is perfect for people who have never implemented an ERP system before or used OpenERP, or for those who would like to learn more advanced features, such as creating your own custom modules.

  12. Molecular dynamics simulation of the thermosensitivity of the human connexin 26 hemichannel

    Science.gov (United States)

    Alizadeh, Hadi; Davoodi, Jamal; Zeilinger, Carsten; Rafii-Tabar, Hashem

    2018-01-01

    Connexin hemichannels mediate cytoplasm and extracellular milieu communication by exchanging a variety of cytoplasmic molecules and ions. These hemichannels can be regulated by external stimuli such as mechanical stress, applied voltage, pH and temperature changes. Although there are many studies on structures and functions of connexin 26 in contexts of pH, ion concentration and voltage, employing computational methods, no such study has been performed so far involving temperature changes. In this study, using molecular dynamics simulation, we investigate thermosensitivity of the human Connexin 26 hemichannel. Our results show that the channel approaches a structurally closed state at lower temperature compared to higher temperature. This is in fair agreement with experimental results that indicate channel closure at lower temperature. Furthermore, our MD simulation results show that some regions of connexin 26 hemichannel are more sensitive to temperature compared to other regions. Whereas the intercellular half of the channel does not show any considerable response to temperature during the simulation time accessible in this study, the cytoplasmic half approaches a closed structural state at lower temperature compared to the higher temperature. Specifically, our results suggest that the cytoplasmic loop, the cytoplasmic half of the second transmembrane helix, and the N-terminus helix play a dominant role in temperature gating.

  13. Immunohistochemistry of connexin 43 throughout anterior pituitary gland in a transgenic rat with green fluorescent protein-expressing folliculo-stellate cells.

    Science.gov (United States)

    Horiguchi, Kotaro; Fujiwara, Ken; Kouki, Tom; Kikuchi, Motoshi; Yashiro, Takashi

    2008-12-01

    Folliculo-stellate (FS) cells in the anterior pituitary gland have been speculated to possess multifunctional properties. Because gap junctions (GJ) have been identified between FS cells, FS cells may be interconnected electrophysiologically by GJ and serve as signal transmission networks to modulate hormone release in the anterior pituitary gland. But whether GJ are localized among FS cells from the pars tuberalis through the pars distalis is unclear. The S100b-GFP transgenic rat has recently been generated, which expresses green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary. This model is expected to be a powerful tool for studies of FS cells. The purpose of the present paper was therefore to examine the localization of GJ on connexin 43 immunohistochemistry throughout the anterior pituitary gland of S100b-GFP rats under confocal laser microscopy. The localization patterns of FS cells was also observed in primary culture of anterior pituitary cells and the question of whether GJ between FS cells are reconstructed in vitro was investigated. In vivo studies showed that GJ were present specifically between FS cells from the pars tuberalis to the pars distalis in the anterior pituitary gland. The appearance of FS cells was distinguished into two types, with localization of GJ differing between types. In vitro, it was observed for the first time that FS cells in primary culture could be categorized into two types. In vivo localization of GJ between FS cells was reconstructed in vitro. These morphological observations are consistent with the hypothesis that FS cells form an electrophysiological network throughout the anterior pituitary for signal transmission.

  14. ERP as a Service

    OpenAIRE

    Mach, Jan

    2012-01-01

    This work is focused on the problematics of ERP as a Service and its main goal is to identify opportunities for new Czech providers of ERP as a Service. In theoretical part of this work at first is described that, what is provided by ERP as a Service. Further off is this part focused on that, how and under which terms can be and should be ERP as a Service provided. In last chapter of this part are presented world IT trends (for example Lean IT) and its relation to ERP as a Service. In second ...

  15. A novel 9-class auditory ERP paradigm driving a predictive text entry system

    Directory of Open Access Journals (Sweden)

    Johannes eHöhne

    2011-08-01

    Full Text Available Brain-Computer Interfaces (BCIs based on Event Related Potentials (ERPs strive for offering communication pathways which are independent of muscle activity. While most visual ERP-based BCI paradigms require good control of the user's gaze direction, auditory BCI paradigms overcome this restriction. The present work proposes a novel approach using Auditory Evoked Potentials (AEP for the example of a multiclass text spelling application. To control the ERP speller, BCI users focus their attention to two-dimensional auditory stimuli that vary in both, pitch (high/medium/low and direction (left/middle/right and that are presented via headphones. The resulting nine different control signals are exploited to drive a predictive text entry system. It enables the user to spell a letter by a single 9-class decision plus two additional decisions to confirm a spelled word.This paradigm - called PASS2D - was investigated in an online study with twelve healthy participants. Users spelled with more than 0.8 characters per minute on average (3.4 bits per minute which makes PASS2D a competitive method. It could enrich the toolbox of existing ERP paradigms for BCI end users like late-stage ALS patients.

  16. The interoperability force in the ERP field

    Science.gov (United States)

    Boza, Andrés; Cuenca, Llanos; Poler, Raúl; Michaelides, Zenon

    2015-04-01

    Enterprise resource planning (ERP) systems participate in interoperability projects and this participation sometimes leads to new proposals for the ERP field. The aim of this paper is to identify the role that interoperability plays in the evolution of ERP systems. To go about this, ERP systems have been first identified within interoperability frameworks. Second, the initiatives in the ERP field driven by interoperability requirements have been identified from two perspectives: technological and business. The ERP field is evolving from classical ERP as information system integrators to a new generation of fully interoperable ERP. Interoperability is changing the way of running business, and ERP systems are changing to adapt to the current stream of interoperability.

  17. An Auditing Approach for ERP Systems Examining Human Factors that Influence ERP User Satisfaction

    Directory of Open Access Journals (Sweden)

    Theodoros MITAKOS

    2010-01-01

    Full Text Available This paper tries to connect the successful implementation and operation of the ERP (Enterprise Resource Planning information systems with people and their characteristics through a pilot survey. It examines the human factors that influence ERP user satisfaction. The presented survey tests 14 hypotheses and is based on the model developed by Zviran, Pliskin & Levin [21]. An additional factor has been added to the specified model, the self-efficacy factor analyzed by Bandura [1]. The results are based on 250 ERP users that responded to the survey. The key findings that were revealed by data analysis were that none of the human socio-demographic characteristics do influence ERP user satisfaction. Additionally it was found that perceived usefulness and self-efficacy are the key directors of the ERP user satisfaction. Moreover suggestions are given about how the companies should handle ERP usage in order to develop the prerequisites for increasing user satisfaction and productivity accordingly.

  18. MAXIMIZING THE BENEFITS OF ERP SYSTEMS

    Directory of Open Access Journals (Sweden)

    Paulo André da Conceição Menezes

    2010-04-01

    Full Text Available The ERP (Enterprise Resource Planning systems have been consolidated in companies with different sizes and sectors, allowing their real benefits to be definitively evaluated. In this study, several interactions have been studied in different phases, such as the strategic priorities and strategic planning defined as ERP Strategy; business processes review and the ERP selection in the pre-implementation phase, the project management and ERP adaptation in the implementation phase, as well as the ERP revision and integration efforts in the post-implementation phase. Through rigorous use of case study methodology, this research led to developing and to testing a framework for maximizing the benefits of the ERP systems, and seeks to contribute for the generation of ERP initiatives to optimize their performance.

  19. Studi Mengenai Peneriamaan system ERP: EnhancementTerhadap Model Penerimaan Sistem ERP Berbasis Technoloy Acceptance Model

    OpenAIRE

    Govindaraju, Rajesri; de Bruijn, E.J.; Govindaraju, R.; Indriany, Nenny

    2007-01-01

    Dalam penelitian dibangun model yang menjelaskan penerimaan user terhadap sistem ERP yang diimplementasikan, serta melakukan survey untuk menguji hipotesis. Dengan model yang dibangun dikaji pengaruh attitude toward ERP system use dan ERP symbolic adoption yang mengacu pada penerimaan mental secara sukarela terhadap sistem ERP. Model yang digunakan dalam penelitian ini adalah adaptasi dari model TAM yang dikembangkan oleh Nah et al (2004) dan menambahkan lima konstruk baru yang berkaitan deng...

  20. Iconic gestures prime related concepts: an ERP study.

    Science.gov (United States)

    Wu, Ying Croon; Coulson, Seana

    2007-02-01

    To assess priming by iconic gestures, we recorded EEG (at 29 scalp sites) in two experiments while adults watched short, soundless videos of spontaneously produced, cospeech iconic gestures followed by related or unrelated probe words. In Experiment 1, participants classified the relatedness between gestures and words. In Experiment 2, they attended to stimuli, and performed an incidental recognition memory test on words presented during the EEG recording session. Event-related potentials (ERPs) time-locked to the onset of probe words were measured, along with response latencies and word recognition rates. Although word relatedness did not affect reaction times or recognition rates, contextually related probe words elicited less-negative ERPs than did unrelated ones between 300 and 500 msec after stimulus onset (N400) in both experiments. These findings demonstrate sensitivity to semantic relations between iconic gestures and words in brain activity engendered during word comprehension.

  1. Studi Mengenai Peneriamaan system ERP: EnhancementTerhadap Model Penerimaan Sistem ERP Berbasis Technoloy Acceptance Model

    NARCIS (Netherlands)

    Govindaraju, Rajesri; de Bruijn, E.J.; Govindaraju, R.; Indriany, Nenny

    2007-01-01

    Dalam penelitian dibangun model yang menjelaskan penerimaan user terhadap sistem ERP yang diimplementasikan, serta melakukan survey untuk menguji hipotesis. Dengan model yang dibangun dikaji pengaruh attitude toward ERP system use dan ERP symbolic adoption yang mengacu pada penerimaan mental secara

  2. Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32

    Science.gov (United States)

    Green, L. M.; Tran, D. T.; Murray, D. K.; Rightnar, S. S.; Todd, S.; Nelson, G. A.

    2002-01-01

    The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after gamma irradiation revealed that early-passage follicular cultures had significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures (0.11 Gy(-1)) (P 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in gamma-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had alpha values that were not significantly different whether cells expressed functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)), or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower alpha values from the gamma-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the expression of connexin 32-type gap junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation was independent of their ability to communicate through connexin 32 gap junctions. (3) The fact that the beta components of the survival curves from both gamma rays and proton beams were

  3. Factores diferenciales entre los ERP de software libre (FSW ERP) y los ERP propietarios

    OpenAIRE

    Oltra Badenes, Raúl Francisco; Gil Gómez, Hermenegildo; Bellver López, Rosa Ana

    2011-01-01

    [ES] : Los sistemas de información son actualmente uno de los factores clave en el desarrollo y competitividad de la empresa. Dentro de los sistemas de información, los ERP son posiblemente los sistemas que mayor impacto tienen en la gestión de las empresas. En su continua evolución, una de las nuevas tendencias en el desarrollo de ERP, es la del software libre o Free Software. Sin embargo, prácticamente no hay estudios que centren su atención en la aplicación del software libre a...

  4. User Satisfaction Issues in ERP Projects

    OpenAIRE

    Shahin Dezdar

    2012-01-01

    Over the past few years, companies in developing countries have implemented enterprise resource planning (ERP) systems. Regardless of the various benefits of the ERP system, its adoption and implementation have not been without problems. Many companies have assigned considerable organizational resources to their ERP projects, but have encountered unexpected challenges. Neglecting a number of important factors in ERP projects might lead to failure instead of success. User ...

  5. The role of the Cx43 C-terminus in GJ plaque formation and internalization

    International Nuclear Information System (INIS)

    Wayakanon, Praween; Bhattacharjee, Rajib; Nakahama, Ken-ichi; Morita, Ikuo

    2012-01-01

    Highlights: ► Cx43-GFP or -DsRed fusion proteins were expressed in HeLa cells. ► Roles of C-terminus were examined using various mutants. ► Gap junction plaque size was dependent on the length of C-terminus. ► C-terminus dependent gap junction plaque internalization was observed. -- Abstract: Connexin 43 (Cx43) is a major gap junction (GJ) protein found in many mammalian cell types. The C-terminal (CT) domain of Cx43 has unique characteristics in terms of amino acid (aa) sequence and its length differs from other connexins. This CT domain can be associated with protein partners to regulate GJ assembly and degradation, which results in the direct control of gap junction intercellular communication (GJIC). However, the essential roles of the CT regions involved in these mechanisms have not been fully elucidated. In this study, we aimed to investigate the specific regions of Cx43CT involved in GJ formation and internalization. Wild type Cx43 (382aa) and 10 CT truncated mutants were stably expressed in HeLa cells as GFP or DsRed tagged proteins. First, we found that the deletion of 235–382aa from Cx43 resulted in failure to make GJ and establish GJIC. Second, the Cx43 with 242–382aa CT deletion could form functional GJs and be internalized as annular gap junctions (AGJs). However, the plaques consisting of Cx43 with CT deletions (Δ242–382aa to Δ271–382aa) were longer than the plaques consisting of Cx43 with CT deletions (Δ302–382aa). Third, co-culture experiments of cells expressing wild type Cx43 (382) with cells expressing Cx43CT mutants revealed that the directions of GJ internalization were dependent on the length of the respective CT. Moreover, a specific region, 325–342aa residues of Cx43, played an important role in the direction of GJ internalization. These results showed the important roles of the Cx43 C-terminus in GJ expression and its turnover.

  6. Sistemas ERP: características, custos e tendências ERP systems: characteristics, implementation cost, tendencies

    Directory of Open Access Journals (Sweden)

    Thais Cássia Cabral Padilha

    2005-04-01

    Full Text Available Muitas empresas estão adotando Sistemas ERP devido a várias razões, tais como: decepção com sistemas incompatíveis, incapacidade do Departamento de Tecnologia de Informação em realizar a integração entre os sistemas existentes atualmente na empresa e outros motivos que influenciam diretamente a competitividade da Empresa. Neste contexto, este artigo apresenta as principais características de Sistemas ERP, suas vantagens e desvantagens, bem como os custos envolvidos na sua implementação. Finalmente, as tendências e o futuro de Sistemas ERP são comentados.Several Companies are adopting ERP systems due to different reasons, such as: deceptions with incompatible systems, incapacity of Technology Information Department of doing integration among current systems, and other reasons which have direct influence in Company's competitiveness. In this context, this work presents the main ERP system characteristics, and the advantages, disadvantages and costs involved with its implementation. Besides this, the tendencies and the future for ERP systems are commented.

  7. Validation of the Emotiv EPOC® EEG gaming system for measuring research quality auditory ERPs

    Science.gov (United States)

    Mousikou, Petroula; Mahajan, Yatin; de Lissa, Peter; Thie, Johnson; McArthur, Genevieve

    2013-01-01

    Background. Auditory event-related potentials (ERPs) have proved useful in investigating the role of auditory processing in cognitive disorders such as developmental dyslexia, specific language impairment (SLI), attention deficit hyperactivity disorder (ADHD), schizophrenia, and autism. However, laboratory recordings of auditory ERPs can be lengthy, uncomfortable, or threatening for some participants – particularly children. Recently, a commercial gaming electroencephalography (EEG) system has been developed that is portable, inexpensive, and easy to set up. In this study we tested if auditory ERPs measured using a gaming EEG system (Emotiv EPOC®, www.emotiv.com) were equivalent to those measured by a widely-used, laboratory-based, research EEG system (Neuroscan). Methods. We simultaneously recorded EEGs with the research and gaming EEG systems, whilst presenting 21 adults with 566 standard (1000 Hz) and 100 deviant (1200 Hz) tones under passive (non-attended) and active (attended) conditions. The onset of each tone was marked in the EEGs using a parallel port pulse (Neuroscan) or a stimulus-generated electrical pulse injected into the O1 and O2 channels (Emotiv EPOC®). These markers were used to calculate research and gaming EEG system late auditory ERPs (P1, N1, P2, N2, and P3 peaks) and the mismatch negativity (MMN) in active and passive listening conditions for each participant. Results. Analyses were restricted to frontal sites as these are most commonly reported in auditory ERP research. Intra-class correlations (ICCs) indicated that the morphology of the research and gaming EEG system late auditory ERP waveforms were similar across all participants, but that the research and gaming EEG system MMN waveforms were only similar for participants with non-noisy MMN waveforms (N = 11 out of 21). Peak amplitude and latency measures revealed no significant differences between the size or the timing of the auditory P1, N1, P2, N2, P3, and MMN peaks. Conclusions

  8. Validation of the Emotiv EPOC® EEG gaming system for measuring research quality auditory ERPs

    Directory of Open Access Journals (Sweden)

    Nicholas A. Badcock

    2013-02-01

    Full Text Available Background. Auditory event-related potentials (ERPs have proved useful in investigating the role of auditory processing in cognitive disorders such as developmental dyslexia, specific language impairment (SLI, attention deficit hyperactivity disorder (ADHD, schizophrenia, and autism. However, laboratory recordings of auditory ERPs can be lengthy, uncomfortable, or threatening for some participants – particularly children. Recently, a commercial gaming electroencephalography (EEG system has been developed that is portable, inexpensive, and easy to set up. In this study we tested if auditory ERPs measured using a gaming EEG system (Emotiv EPOC®, www.emotiv.com were equivalent to those measured by a widely-used, laboratory-based, research EEG system (Neuroscan.Methods. We simultaneously recorded EEGs with the research and gaming EEG systems, whilst presenting 21 adults with 566 standard (1000 Hz and 100 deviant (1200 Hz tones under passive (non-attended and active (attended conditions. The onset of each tone was marked in the EEGs using a parallel port pulse (Neuroscan or a stimulus-generated electrical pulse injected into the O1 and O2 channels (Emotiv EPOC®. These markers were used to calculate research and gaming EEG system late auditory ERPs (P1, N1, P2, N2, and P3 peaks and the mismatch negativity (MMN in active and passive listening conditions for each participant.Results. Analyses were restricted to frontal sites as these are most commonly reported in auditory ERP research. Intra-class correlations (ICCs indicated that the morphology of the research and gaming EEG system late auditory ERP waveforms were similar across all participants, but that the research and gaming EEG system MMN waveforms were only similar for participants with non-noisy MMN waveforms (N = 11 out of 21. Peak amplitude and latency measures revealed no significant differences between the size or the timing of the auditory P1, N1, P2, N2, P3, and MMN peaks

  9. The Challenge of Implementing an ERP System in a Small and Medium Enterprise--A Teaching Case of ERP Project Management

    Science.gov (United States)

    Xu, Hongjiang; Rondeau, Patrick J.; Mahenthiran, Sakthi

    2011-01-01

    Enterprise Resource Planning (ERP) system implementation projects are notoriously risky. While large-scale ERP cases continue to be developed, relatively few new ERP cases have been published that further ERP implementation education in small to medium size firms. This case details the implementation of a new ERP system in a medium sized…

  10. ERP SOLUTIONS FOR SMEs

    Directory of Open Access Journals (Sweden)

    TUTUNEA MIHAELA FILOFTEIA

    2012-09-01

    Full Text Available The integration of activities, the business processes as well as their optimization, bring the perspective of profitable growth and create significant and competitive advantages in any company. The adoption of some ERP integrated software solutions, from SMEs’ perspective, must be considered as a very important management decision in medium and long term. ERP solutions, along with the transparent and optimized management of all internal processes, also offer an intra and inter companies collaborative platform, which allows a rapid expansion of activities towards e- business and mobile-business environments. This material introduces ERP solutions for SMEs from commercial offer and open source perspective; the results of comparative analysis of the solutions on the specific market, can be an useful aid to the management of the companies, in making the decision to integrate business processes, using ERP as a support.

  11. MAXIMIZING THE BENEFITS OF ERP SYSTEMS

    OpenAIRE

    Paulo André da Conceição Menezes; Fernando González-Ladrón-de-Guevara

    2010-01-01

    The ERP (Enterprise Resource Planning) systems have been consolidated in companies with different sizes and sectors, allowing their real benefits to be definitively evaluated. In this study, several interactions have been studied in different phases, such as the strategic priorities and strategic planning defined as ERP Strategy; business processes review and the ERP selection in the pre-implementation phase, the project management and ERP adaptation in the implementation phase, as well as th...

  12. ERP and CRM Data Integration

    Directory of Open Access Journals (Sweden)

    Željko Tomić

    2016-05-01

    As a rule, the CRM and ERP systems contain separate databases even if they come from the same manufacturer. Such separately kept databases also lead to separate basic records (identifiers, which primarily relate to business partners, items and services. This may create problems with updating and maintaining consistency of the data within the information system of a company. The CRM and ERP systems usually overlap in certain segments of business processes (e.g., orders, order confirmations, quotations, etc., thus potentially creating redundant information and documents. More often than not, the CRM and ERP also differ in terms of technology, both by their vertical architectures and with regard to the DBMS and API support. The objective of this paper is to generate an ERP-CRM integration data model by way of optimising the relevant processes and costs, and to provide details about the processes of integration of the logical and physical data models. The structural integration of the ERP-CRM databases provide the integration services that ensure all the necessary functionalities in various interface logics and technologies with regard to software solutions and applications given, or used for local adaptations of the existing ERP and CRM applications.

  13. Stakeholder Salience in ERP Projects

    OpenAIRE

    Salhotra, Eashan

    2014-01-01

    The aim of this study is to examine stakeholder involvement in an Enterprise Resource Planning (ERP) System project that involves implementation and improvement of the implemented system. The study targets stakeholders, their classification, and their degree of importance during different phases of an ERP project life cycle, i.e. planning, implementation, stabilisation and improvement. The study shows that stakeholder involvement and their salience vary along the ERP project life cycle a...

  14. AMES: Towards an Agile Method for ERP Selection

    OpenAIRE

    Juell-Skielse, Gustaf; Nilsson, Anders G.; Nordqvist, Andreas; Westergren, Mattias

    2012-01-01

    Conventional on-premise installations of ERP are now rapidly being replaced by ERP as service. Although ERP becomes more accessible and no longer requires local infrastructure, current selection methods do not take full advantage of the provided agility. In this paper we present AMES (Agile Method for ERP Selection), a novel method for ERP selection which better utilizes the strengths of service oriented ERP. AMES is designed to shorten lead time for selection, support identification of essen...

  15. ERP inside Large Organizations

    Directory of Open Access Journals (Sweden)

    Constantin Daniel AVRAM

    2010-01-01

    Full Text Available Many large companies in Romania are still functioning without an ERP system. Instead they are using traditional application systems built around the strong boundaries of specific functions: finance, selling, HR, production. An ERP will offer lots of advantages among which the integration of functionalities and support for top management decisions. Although the total cost of ownership is not small and there are some risks when implementing an ERP inside large and very large organizations, having such a system is mandatory. Choosing the right product and vendor and using a correct risk management strategy, will ensure a successful implementation.

  16. Analisis Dampak Penerapan Sistem ERP terhadap Kinerja Pengguna

    Directory of Open Access Journals (Sweden)

    Aries Wicaksono

    2015-05-01

    Full Text Available The background of this research was to determine how the impact of the implementation and use of ERP systems on user performance and the factors that affect the successful implementation of the ERP system so that it can have a positive impact for users of the ERP system after the implementation of ERP systems. This study aims to Knowing whether the implementation of ERP systems on firm performance impact on ERP users in the company and Produce conclusions in the form of an evaluation of the implementation of ERP in the company in order to provide a positive impact on user performance. The model used to evaluate the impact of the implementation of the ERP system is Quantity of Work, Quality of Work, Job Knowledge, Creativeness Cooperation, Dependability, Initiative, personal qualities. The method used in this research is descriptive qualitative method of analytical and evaluative, by analyzing the impact of the implementation of the ERP system to the components of the user's performance. The results obtained are implementing ERP systems have a positive impact on user performance components.

  17. ERP Effort Estimation Based on Expert Judgments

    NARCIS (Netherlands)

    Erasmus, I.P.; Daneva, Maia; Demirors, O.; Abran, A.

    2013-01-01

    A new technology shift brings to the ERP domain a change in the industry and a new platform build on in-memory optimized databases, introduced and known as SAP HANA [1]. This technology shift in the ERP domain led to SAP's ERP on HANA, the solution where the ERP suite is offered on the same platform

  18. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    Science.gov (United States)

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  19. Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep.

    Directory of Open Access Journals (Sweden)

    Joanne O Davidson

    Full Text Available Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103-104 d gestational age. Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6 or vehicle infusion for controls (occlusion-vehicle group, n = 7. Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05, with reduced neuronal loss in the caudate and putamen (p<0.05, but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05 and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05, with a significant increase in proliferation (p<0.05. Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia.

  20. Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep

    Science.gov (United States)

    Davidson, Joanne O.; Drury, Paul P.; Green, Colin R.; Nicholson, Louise F.; Bennet, Laura; Gunn, Alistair J.

    2014-01-01

    Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103–104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6) or vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05), with reduced neuronal loss in the caudate and putamen (p<0.05), but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05) and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05), with a significant increase in proliferation (p<0.05). Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia. PMID:24865217

  1. ERP ASSIMILATION: AN END-USER APPROACH

    Directory of Open Access Journals (Sweden)

    Hurbean Luminita

    2013-07-01

    The paper discusses the ERP adoption based on the IT assimilation theory. The ERP lifecycle is associated with the IT assimilation steps. We propose a distribution of these steps along the lifecycle. Derived from the findings in the reviewed literature we will focus the cultural factors, in particular those related to the end-users (determined as a major impact factor in our previous study: Negovan et al., 2011. Our empirical study is centred on the end-users perspective and it tries to determine if and how their behaviour affects the achievement of the ERP assimilation steps. The paper reasons that organizations that understand the IT assimilation steps correlated to the ERP implementation critical factors are more likely to implement and use ERP successfully.

  2. Selection Process of ERP Systems

    OpenAIRE

    Molnár, Bálint; Szabó, Gyula; Benczúr, András

    2013-01-01

    Background: The application and introduction of ERP systems have become a central issue for management and operation of enterprises. The competition on market enforces the improvement and optimization of business processes of enterprises to increase their efficiency, effectiveness, and to manage better the resources outside the company. The primary task of ERP systems is to achieve the before-mentioned objectives. Objective: The selection of a particular ERP system has a decisive effect on th...

  3. Successful Issues for Implementing Enterprise Resource Planning (ERP)

    Institute of Scientific and Technical Information of China (English)

    LI Bing-guang; Michael W. Riley

    2003-01-01

    Enterprise Resource Planning (ERP) systems have emerged and have matured to become the core of successful information management and the enterprise backbone of organizations for applications such as e-business, Supply Chain Management (SCM) and Customer Relation Management (CRM). This paper theorizes and generalizes the important steps and factors for ERP implementation success. First, the paper gives an introduction to ERP and the relationships between MRP, MPRII and ERP. The benefits and motivations of adoption of ERP systems are introduced. Steps for ERP system selection and implementation are presented. The paper proposes a qualitative analysis of the key factors that affect a successful ERP implementation.

  4. TRENDI NA PODROČJU CELOVITIH INFORMACIJSKIH REŠITEV (ERP)

    OpenAIRE

    Bednjanič, Aljaž

    2012-01-01

    V diplomskem seminarju so predstavljeni trendi na področju rešitev ERP. Ponudniki rešitev ERP nenehno spreminjajo in dopolnjujejo svoje produkte ter jim dodajajo nove funkcionalnosti. Predstavljeni so naslednji trendi: x-ERP, zunanje izvajanje rešitev ERP, rešitev ERP kot storitev (SaaS ERP), ERP v oblaku in mobilni dostop. Zagotovo je najzanimivejša novost ERP v oblaku. Ta nudi številne prednosti, a obstaja veliko vprašanj, povezanih z varnostjo podatkov v oblaku. Pogledali smo, kako je z zu...

  5. Validation of the Emotiv EPOC(®) EEG gaming system for measuring research quality auditory ERPs.

    Science.gov (United States)

    Badcock, Nicholas A; Mousikou, Petroula; Mahajan, Yatin; de Lissa, Peter; Thie, Johnson; McArthur, Genevieve

    2013-01-01

    Background. Auditory event-related potentials (ERPs) have proved useful in investigating the role of auditory processing in cognitive disorders such as developmental dyslexia, specific language impairment (SLI), attention deficit hyperactivity disorder (ADHD), schizophrenia, and autism. However, laboratory recordings of auditory ERPs can be lengthy, uncomfortable, or threatening for some participants - particularly children. Recently, a commercial gaming electroencephalography (EEG) system has been developed that is portable, inexpensive, and easy to set up. In this study we tested if auditory ERPs measured using a gaming EEG system (Emotiv EPOC(®), www.emotiv.com) were equivalent to those measured by a widely-used, laboratory-based, research EEG system (Neuroscan). Methods. We simultaneously recorded EEGs with the research and gaming EEG systems, whilst presenting 21 adults with 566 standard (1000 Hz) and 100 deviant (1200 Hz) tones under passive (non-attended) and active (attended) conditions. The onset of each tone was marked in the EEGs using a parallel port pulse (Neuroscan) or a stimulus-generated electrical pulse injected into the O1 and O2 channels (Emotiv EPOC(®)). These markers were used to calculate research and gaming EEG system late auditory ERPs (P1, N1, P2, N2, and P3 peaks) and the mismatch negativity (MMN) in active and passive listening conditions for each participant. Results. Analyses were restricted to frontal sites as these are most commonly reported in auditory ERP research. Intra-class correlations (ICCs) indicated that the morphology of the research and gaming EEG system late auditory ERP waveforms were similar across all participants, but that the research and gaming EEG system MMN waveforms were only similar for participants with non-noisy MMN waveforms (N = 11 out of 21). Peak amplitude and latency measures revealed no significant differences between the size or the timing of the auditory P1, N1, P2, N2, P3, and MMN peaks

  6. ERP Software Selection Model using Analytic Network Process

    OpenAIRE

    Lesmana , Andre Surya; Astanti, Ririn Diar; Ai, The Jin

    2014-01-01

    During the implementation of Enterprise Resource Planning (ERP) in any company, one of the most important issues is the selection of ERP software that can satisfy the needs and objectives of the company. This issue is crucial since it may affect the duration of ERP implementation and the costs incurred for the ERP implementation. This research tries to construct a model of the selection of ERP software that are beneficial to the company in order to carry out the selection of the right ERP sof...

  7. Implementing ERP-systems with accelerated ERP more efficient and quickly – a best practice

    Directory of Open Access Journals (Sweden)

    Yücel Yılmaz

    2011-07-01

    Full Text Available This best practice deals with the Accelerated ERP Methodology and the relevant project steps, while defining the main parameters such as administration, system availability, security and planning the project and the network. In this case, the implementation project in a food company (JKL, name altered is analyzed within the scope of project management, and it is described how this methodology put into practice. With this study, efficiency and quickness of an ERP implementation with the Accelerated ERP Methodology is pointed out.

  8. ERP in large Danish enterprises: Implications for SCM

    DEFF Research Database (Denmark)

    Møller, Charles

    2004-01-01

    This paper argues that with the present state of Enterprise Resource Planning (ERP) adoption by the companies, the potential benefits of Supply Chain Management (SCM) and integration is about to be unleashed. This paper presents the results and the implications of a survey on ERP adoption...... in the 500 largest Danish enterprises. The study is based on telephone interviews with ERP managers in 88.4% of the "top 500" enterprises in Denmark. Based on the survey, the paper suggests the following four propositions: (i) ERP has become the pervasive infrastructure; (ii) ERP has become a contemporary...... technology; (iii) ERP adoption has matured; and (iv) ERP adoption is converging towards a dominant design. Finally, the paper discusses the general implications of the surveyed state of practice on the SCM research challenges. Consequently we argue that research needs to adjust its conceptions of the ERP...

  9. Higher Education ERP: Lessons Learned.

    Science.gov (United States)

    Swartz, Dave; Orgill, Ken

    2001-01-01

    Shares experiences and lessons learned by chief information officers of large universities about enterprise resource planning (ERP). Specifically, provides a framework for approaching an ERP that could save universities millions of dollars. (EV)

  10. Healthcare Firms and the ERP Systems

    Directory of Open Access Journals (Sweden)

    A. Garefalakis

    2016-04-01

    Full Text Available With the continuous and drastic changes due to the economic crisis, along with the increasing market demands, major reforms are initiated in the healthcare sector in order to improve the quality of healthcare and operational efficiency, while reducing costs and optimizing back-end operations. ERP systems have been the basic technological infrastructure to many sectors as well as healthcare. The main objective of this study is to discuss how the adoption of ERP systems in healthcare organizations improves their functionality, simplifies their business processes, assure the quality of care services and helps their management accounting and controlling. This study presents also the stages required for the implementation of ERP system in healthcare organizations. This study utilizes a literature review in order to reach the research conclusions. Specifically, through related case studies and research, it examines how ERP systems are used to evaluate the better functionality of the healthcare organizations, addressing in parallel important problems, and possible malfunctions. The implementation of ERP systems in healthcare organizations promises to evolve and align strictly to the organizations’ corporate objectives and high-levels of healthcare quality. In order to accomplish this goal, the right decisions should be made by the managers of the healthcare organization regarding the choice of the appropriate ERP system following its installation and its application. Limited research exists on the significance ERP systems implementation in healthcare organizations, while possible dysfunctions and challenges during its installation and implementation are recorded. Therefore, new evidence in the significance of ERP systems in healthcare organization is provided.

  11. ERP-systemer i Danmark

    DEFF Research Database (Denmark)

    Møller, Charles; Kræmmergaard, Pernille

    2004-01-01

    Denne artikel beskriver ERP systemers udbredelse blandt store virksomheder i Danmark. Artiklen bygger på projektet "Virksomhedssystemer i Danmark (VIDK) 2003". VIDK 2003 er en undersøgelse af de 500 største danske virksomheders brug af ERP. Undersøgelsen, der har en har en svarprocent på 88,4%, e...

  12. Chinese Cultural Implications for ERP Implementation

    Directory of Open Access Journals (Sweden)

    Mukesh Srivastava

    2009-05-01

    Full Text Available Implementation of an enterprise resource planning (ERP system in a global environment can be fragmented due to the internal enterprise culture, which is representative of societal culture. In China, this is especially true due to the nationalistic culture of business. The way ERP systems are perceived, treated, and integrated within the business plays a critical role in the success or failure of the implementation. When a Western developed ERP system is implemented in a country where the culture differs greatly from that of the developer, implementation may require localization in order to be successful. In doing so, strategic benefits of ERP systems may be diminished. This research paper looks into the characteristics of Chinese localization by Western vendors and the implications to the Chinese enterprise. Keywords: ERP, Chinese Cultural Implications, Societal Culture, Strategy

  13. Firemní ERP systém

    OpenAIRE

    Komárek, Lukáš

    2010-01-01

    Tato bakalářská práce pojednává o problematice tvorby ERP systému na platformě .NET Framework s využitím Microsoft technologií. Jednotlivé kapitoly seznámí čtenáře s analýzou, návrhem a implementací vlastního ERP systému. Čtenář bude podrobněji seznámen se zařazením a komponentami ERP systému, moderními vývojovými technologiemi a nástroji, příkladem návrhu modulů a funkcí ERP systému včetně implementace a nasazení aplikace ERP systému. This thesis focuses on the issues while creating the E...

  14. Intracerebroventricular Injection of Lipopolysaccharide Increases Gene Expression of Connexin32 Gap Junction in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Mohammad Abbasian

    2013-11-01

    Full Text Available Introduction: Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx. Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 – among Connexins– is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS on Cx32 gene and protein expressions in rat hippocampus is evaluated. Methods: LPS (2.5μg/rat was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus. Results: Significant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P<0.001. However, no significant change was observed in Cx32 protein level. Conclusion: LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined.

  15. Risks in ERP projects implementation : How communication and business processes re-engineering risks effect ERP projects

    OpenAIRE

    Aslanyan, Armine

    2017-01-01

    Enterprise Resource Planning (ERP) systems have been regarded as one of the most important information technology developments in the past decades. While ERP systems provide the potential to bring substantial benefits, their implementations are characterized by large capital outlay, long duration, and high might be a solution to ensure the success of ERP system implementations in organizations. The overall objective of this research is to to provide detailed analysis and impacts of busines...

  16. Mobility Integration of ERP systems

    Directory of Open Access Journals (Sweden)

    Álvaro LOZANO

    2015-03-01

    Full Text Available Nowadays a lot of enterprises work with ERP systems. It usefulness is generally used in office environments and different enterprises which offer this software are developing mobile applications. These mobile applications work with their own system and they don’t usually work in other platforms. Currently any mobile application can communicate with more than one ERP system because each one has its own communications methods. This article presents a system that expect unify the communication between different ERP systems and allows mobile applications to communicate with them in a homogeneous way.

  17. The invisible accounting side of ERP systems

    Directory of Open Access Journals (Sweden)

    Iliyan Dimitrov

    2017-12-01

    Full Text Available ERP (Enterprise Resource planning systems are widely used in many organizations, including companies in Bulgaria. Depending of the point of view statistical results of their implementation in recent years are contradictory (Infostat, 2017, (Eurostat, 2017. This paper reveals an overview of researchers and practitioners’ interpretations, who express opinion for an essence and advantages of adopting ERP systems. In academic and professional discussions one potential benefit stays invisible. The purpose of this publication is to provide new sight of essence and potential benefits which are given with ERP implementation. Some advantages of ERP systems are discussed. Some aspects of the links between ERP systems, management accounting and financial accounting are described.

  18. 7 CFR 1730.28 - Emergency Restoration Plan (ERP).

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Emergency Restoration Plan (ERP). 1730.28 Section... § 1730.28 Emergency Restoration Plan (ERP). (a) Each borrower with an approved RUS electric program loan as of October 12, 2004 shall have a written ERP no later than January 12, 2006. The ERP should be...

  19. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Christensen, A H; Andersen, C B; Tybjærg-Hansen, A

    2011-01-01

    Christensen AH, Andersen CB, Tybjærg-Hansen A, Haunso S, Svendsen JH. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right...... with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c.1073C> T......; in two related patients) and one novel variant (c.705+ 7G> A; in one patient) of unknown significance. All three patients fulfilled Task Force criteria and did not carry mutations in any other ARVC-related gene. Immunostaining with TMEM43 antibody showed intense staining of the sarcolemma. The signal...

  20. Opening of pannexin and connexin based-channels increases the excitability of nodose ganglion sensory neurons.

    Directory of Open Access Journals (Sweden)

    Mauricio Antonio Retamal

    2014-06-01

    Full Text Available Satellite glial cells (SGCs are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents the formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with sensory neurons. However, the molecular mechanism involved in this cellular communication is unknown. In the central nervous system, astrocytes present connexin43 (Cx43 hemichannels and pannexin1 (Panx1 channels, and their opening allows the release of signal molecules, such as ATP and glutamate. We propose that these channels could play a role in the glia-neuron communication in sensory ganglia. Therefore, we studied the expression and function of Cx43 and Panx1 in rat and mouse nodose-petrosal-jugular complex (NPJc by confocal immunofluorescence, molecular and electrophysiological techniques. Cx43 and Panx1 were detected in SGCs and sensory neurons, respectively. In the rat and mouse, the electrical activity of vagal nerve increased significantly after nodose neurons were exposed to Ca2+/ Mg2+-free solution, a condition that increases the open probability of Cx hemichannels. This response was partially mimicked by a cell-permeable peptide corresponding to the last 10 amino acids of Cx43 (TAT-Cx43CT. Enhanced neuronal activity was reduced by Cx hemichannel, Panx1 channel and P2X7 receptor blockers. Moreover, the role of Panx1 was confirmed in NPJc, because Panx1 knockout mouse showed a reduced increase of neuronal activity induced by Ca2+/Mg2+-free extracellular conditions. Data suggest that Cx hemichannels and Panx channels serve as paracrine communication pathways between SGCs and neurons by modulating the excitability of sensory neurons.

  1. Molecular cloning, functional expression, and tissue distribution of a novel human gap junction-forming protein, connexin-31.9. Interaction with zona occludens protein-1

    NARCIS (Netherlands)

    Nielsen, Peter A; Beahm, Derek L; Giepmans, Ben N G; Baruch, Amos; Hall, James E; Kumar, Nalin M

    2002-01-01

    A novel human connexin gene (GJA11) was cloned from a genomic library. The open reading frame encoded a hypothetical protein of 294 amino acid residues with a predicted molecular mass of 31,933, hence referred to as connexin-31.9 (Cx31.9) or alpha 11 connexin. A clone in GenBank containing the

  2. ERP II: Next-generation Extended Enterprise Resource Planning

    DEFF Research Database (Denmark)

    Møller, Charles

    2004-01-01

    ERP II (ERP/2) systems is a new concept introduced by Gartner Group in 2000 in order to label the latest extensions of the ERP-systems. The purpose of this paper is to explore the next-generation of ERP systems, the Extended Enterprise Resource Planning (EERP or as we prefer to use: e...... impact on extended enterprise architecture.....

  3. ERP II - Next-generation Extended Enterprise Resource Planning

    DEFF Research Database (Denmark)

    Møller, Charles

    2003-01-01

    ERP II (ERP/2) systems is a new concept introduced by Gartner Group in 2000 in order to label the latest extensions of the ERP-systems. The purpose of this paper is to explore the next-generation of ERP systems, the Extended Enterprise Resource Planning (EERP or as we prefer to use: e...... impact on extended enterprise architecture....

  4. High-accuracy Subdaily ERPs from the IGS

    Science.gov (United States)

    Ray, J. R.; Griffiths, J.

    2012-04-01

    Since November 2000 the International GNSS Service (IGS) has published Ultra-rapid (IGU) products for near real-time (RT) and true real-time applications. They include satellite orbits and clocks, as well as Earth rotation parameters (ERPs) for a sliding 48-hr period. The first day of each update is based on the most recent GPS and GLONASS observational data from the IGS hourly tracking network. At the time of release, these observed products have an initial latency of 3 hr. The second day of each update consists of predictions. So the predictions between about 3 and 9 hr into the second half are relevant for true RT uses. Originally updated twice daily, the IGU products since April 2004 have been issued every 6 hr, at 3, 9, 15, and 21 UTC. Up to seven Analysis Centers (ACs) contribute to the IGU combinations. Two sets of ERPs are published with each IGU update, observed values at the middle epoch of the first half and predicted values at the middle epoch of the second half. The latency of the near RT ERPs is 15 hr while the predicted ERPs, based on projections of each AC's most recent determinations, are issued 9 hr ahead of their reference epoch. While IGU ERPs are issued every 6 hr, each set represents an integrated estimate over the surrounding 24 hr. So successive values are temporally correlated with about 75% of the data being common; this fact should be taken into account in user assimilations. To evaluate the accuracy of these near RT and predicted ERPs, they have been compared to the IGS Final ERPs, available about 11 to 17 d after data collection. The IGU products improved dramatically in the earlier years but since about 2008.0 the performance has been stable and excellent. During the last three years, RMS differences for the observed IGU ERPs have been about 0.036 mas and 0.0101 ms for each polar motion component and LOD respectively. (The internal precision of the reference IGS ERPs over the same period is about 0.016 mas for polar motion and 0

  5. 76 FR 47055 - Emergency Restoration Plan (ERP)

    Science.gov (United States)

    2011-08-04

    ... (ERP) AGENCY: Rural Utilities Service, USDA. ACTION: Final rule. SUMMARY: The Rural Utilities Service... 12, 2004, at 69 FR 60541 requiring all borrowers to maintain an Emergency Response Plan (ERP) that... major natural or manmade disaster or other causes. This ERP requirement was not entirely new to the...

  6. Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Leonardo Bocchi

    Full Text Available Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI, lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60 or vehicle (V, n = 55, or sham operated (n = 18. In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration

  7. ERP – a moving target

    DEFF Research Database (Denmark)

    Koch, Christian

    2007-01-01

    Enterprise Resource Planning systems are central elements in longterm wide-ranging design and use networks. Present ERP research focuses on single-enterprise implementation and fails to address important features of the ERP networks such as multi-spatiality, the design of the generic and the dyna...

  8. Hypercompetition in the ERP Industry

    DEFF Research Database (Denmark)

    Antero, Michelle

    2012-01-01

    Applying the Red Queen Theory (RQT), the study posits that an enterprise resource planning (ERP) software vendor counters the Red Queen Effect (RQE) in the hypercompetitive ERP industry by strategically aligning itself with multiple partners to form an ecosystem that can be leveraged for growth...

  9. Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2017-09-01

    Full Text Available Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26, a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action

  10. Design Patterns Application in the ERP Systems Improvements

    Science.gov (United States)

    Jovičić, Bojan; Vlajić, Siniša

    Design patterns application have long been present in software engineering. The same is true for ERP systems in business software. Is it possible that ERP systems do not have a good maintenance score? We have found out that there is room for maintenance improvement and that it is possible to improve ERP systems using design patterns. We have conducted comparative analysis of ease of maintenance of the ERP systems. The results show that the average score for our questions is 64%, with most answers for ERP systems like SAP, Oracle EBS, Dynamics AX. We found that 59% of ERP system developer users are not familiar with design patterns. Based on this research, we have chosen Dynamics AX as the ERP system for examination of design patterns improvement possibilities. We used software metrics to measure improvement possibility. We found that we could increase the Conditional Complexity score 17-fold by introducing design patterns.

  11. Connexin Communication Compartments and Wound Repair in Epithelial Tissue.

    Science.gov (United States)

    Chanson, Marc; Watanabe, Masakatsu; O'Shaughnessy, Erin M; Zoso, Alice; Martin, Patricia E

    2018-05-03

    Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems.

  12. ERP Usage in Practice : Understanding End-Users ‘Acceptance of ERP Systems in Chinese large companies by applying UTAUT model

    OpenAIRE

    Chen, Bo; Zeng, Zili

    2012-01-01

    Introduction: The Enterprise  Resource  Planning system is  an  emerging  technology  that belongs to the scientific discipline of information systems. In simple words the ERP system integrates an organization’s resources and also involves business processes and organiza-tional changes. With the ubiquitous growth of IS investment, ERP systems implementation grows strongly. More and more companies introduced ERP systems. However many ERP implementation success stays at technical perspective. U...

  13. Is Open Source the ERP Cure-All?

    Science.gov (United States)

    Panettieri, Joseph C.

    2008-01-01

    Conventional and hosted applications thrive, but open source ERP (enterprise resource planning) is coming on strong. In many ways, the evolution of the ERP market is littered with ironies. When Oracle began buying up customer relationship management (CRM) and ERP companies, some universities worried that they would be left with fewer choices and…

  14. Factors Manipulate ERP Implementation: An Experiential Study from Pakistan

    OpenAIRE

    Muhammad Jamil Anjum; Saif-ur-rehman Khan

    2015-01-01

    ERP (Enterprise Resource Planning) is a foremost improvement in the arena of organizational management and information system. ERP has the ability to integrate and assimilate the information in an efficient way. ERP is an utmost extensive business management system that presents real-time competences and flawless presentation of information for organizations and businesses. Nevertheless, not all the ERP implementation projects are successful. Implementation of ERP affects the overall processe...

  15. Implementace ERP systémů

    OpenAIRE

    Přívratský, Miroslav

    2008-01-01

    První část této práce uvádí vztah ERP systémů a jiných aplikací běžně zaváděných v podnikových informačních systémech a rozvádí funkcionalitu ERP systémů. Druhá část se poté věnuje detailní kategorizaci ERP produktů z mnoha různých hledisek a analyzuje obecné parametry, podle kterých je možné ERP systémy posuzovat (např. při výběru produktu, který má být implementován). Poslední část je zaměřena na projekty implementace ERP systémů, jejich průběh a hodnocení jejich úspěšnosti. Na závěr práce ...

  16. ERP implementation in hospitals: a case study.

    Science.gov (United States)

    Agarwal, Divya; Garg, Poonam

    2012-01-01

    In a competitive healthcare sector, hospitals have to focus on their processes in order to deliver high-quality care while at the same time reducing costs. Many hospitals have decided to adopt one or another Enterprise Resource Planning (ERP) system to improve their businesses, but implementing an ERP system can be a demanding endeavour. The systems are so difficult to implement that some are successful; many have failed, causing multimillion dollar losses. The challenge of ERP solutions lie in implementation because they are complex, time consuming and expensive too. This paper describes the various process workflows and phases of ERP implementation at Fortis Hospital Cunningham Road, Bangalore, India. This knowledge will provide valuable insights for the researchers and practitioners to understand the different process workflows and to make informed decisions when implementing ERP in any hospital.

  17. Open ERP Odoo guidebook for small and medium enterprises

    OpenAIRE

    Devkota, Arun

    2016-01-01

    ERP systems are vital part of any businesses, For SMEs managing accounting, sales, inventory control, manufacturing, customer relationship all at the same time is not a small task. To meet rising customer demand and market competition business must implement efficient ERP system. Implementing popular high end ERP systems like SAP Business One, Oracle ERP etc. are very costly for SMEs to implement as SMEs lack manpower and financial resources. The current ERP market is poised with various low ...

  18. Success Factors of Large Scale ERP Implementation in Thailand

    OpenAIRE

    Rotchanakitumnuai; Siriluck

    2010-01-01

    The objectives of the study are to examine the determinants of ERP implementation success factors of ERP implementation. The result indicates that large scale ERP implementation success consist of eight factors: project management competence, knowledge sharing, ERP system quality , understanding, user involvement, business process re-engineering, top management support, organization readiness.

  19. Stay on the ERP Treadmill!

    Science.gov (United States)

    Panettieri, Joseph C.

    2007-01-01

    This article discusses University of Central Florida's proactive approach to enterprise resource planning (ERP) and highlights UCF's success with ERP. The article points out that much of this success comes from the strength and management experience of those in leadership positions at UCF, and from the expertise and strong credentials of the team…

  20. ERP Project Management Lessons Learned

    Science.gov (United States)

    Carroll, Timothy D.

    2009-01-01

    Implementing an enterprise resource planning (ERP) system is a major undertaking for any higher education institution, with many challenges along the way. More than three years ago, Roane State Community College began a journey to implement an ERP system. Roane State recently completed a very successful implementation of the SunGard Banner Student…

  1. The Organisational Performance Impact Of ERP Systems On Selected Companies

    Directory of Open Access Journals (Sweden)

    Hart, Colin Anthony

    2014-05-01

    Full Text Available There is a need to determine the performance benefits that firms gain from enterprise resource planning (ERP systems, and the factors that contribute to success. Consequently, the central research problem is: To determine the impact of ERP systems on organisational performance by analysing achieved ERP benefits within the framework of a suitable performance measurement system (PMS, and to investigate the association between critical success factors (CSFs and ERP benefits. A list of expected ERP benefits and CSFs is compiled. Performance measurement models are evaluated, and one model is designed to evaluate ERP impact. ERP experts refine identified ERP benefits and CSFs using structured interviews. These are built into a questionnaire, and used to survey South African (SA companies in manufacturing, mining, and power generation. Results indicate that business benefits are realised by companies that implement ERP systems. By building benefits into the performance measurement model, a positive impact on organisational performance is observed. Although a core list of CSFs is identified, and three associations are found between CSFs and ERP benefits, further research is needed.

  2. Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2014-01-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. - Highlights: • DMBA increases Cx37 and Cx43 expression prior to follicle loss. • During follicle loss both Cx37 and Cx43 expressions are reduced. • CX43 protein is absent in follicle remnants lacking an oocyte.

  3. Connexin 39.9 Protein Is Necessary for Coordinated Activation of Slow-twitch Muscle and Normal Behavior in Zebrafish*

    Science.gov (United States)

    Hirata, Hiromi; Wen, Hua; Kawakami, Yu; Naganawa, Yuriko; Ogino, Kazutoyo; Yamada, Kenta; Saint-Amant, Louis; Low, Sean E.; Cui, Wilson W.; Zhou, Weibin; Sprague, Shawn M.; Asakawa, Kazuhide; Muto, Akira; Kawakami, Koichi; Kuwada, John Y.

    2012-01-01

    In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca2+ transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID:22075003

  4. Aligning ERP and Business Strategy after going live

    DEFF Research Database (Denmark)

    Koch, Christian

    2004-01-01

    Steering enterprises with Enterprise Resource Planning systems (ERP) is not only an issue of implementation and of “once and for all” aligning the ERP system with the strategy of the company, it is a long term exercise. This paper is about managing ERP systems after going live. It is argued...... that companies has to align the ERP systems with the strategy of the company and guidelines as to how this can be achieved is given....

  5. Implementación de OpenErp en PYME

    OpenAIRE

    Bentancur Pisciottano, Ernesto Germán

    2012-01-01

    El proyecto describe el proceso de implementación del ERP OpenErp, en las áreas logística y contable, de una PYME ficticia dedicada al diseño y venta de material informático. El projecte descriu el procés d'implementació de l'ERP OpenERP, a les àrees logística i comptable, d'una PIME fictícia dedicada al disseny i venda de material informàtic.

  6. Enabling Support of Collaborative Cross-enterprise Business Processes for Legacy ERP Systems

    Directory of Open Access Journals (Sweden)

    Gundars Alksnis

    2015-04-01

    Full Text Available In order to create innovative business products, share knowledge between people and businesses, or increase the control and quality of services, more and more often enterprise business processes involve in collaborations by delegating or providing some pieces of work to other enterprises. Necessity to cooperate in the cross-enterprise setting leads to Collaborative Business Processes (CBPs. The difference between CBPs and Business Processes (BPs is in the decentralized coordination, flexible backward recovery, participants notification about the state, efficient adaptability to changes, presence of multiple information systems, and individual authorization settings. In the paper we consider a specific case of CBPs where multiple collaborating partners use Enterprise Resource Planning (ERP system of the same vendor. The vendor can see (e.g., monitor the changes of data elements, but does not have explicit process awareness in the ERP system to support flow of activities in the cross-enterprise setting. The paper also discusses different settings of cross-enterprise CBP and shows simplified enterprise models behind the vendor possibilities to positively impact collaborative processes. The restrictions of the vendor are implicit information flows in BP, diversity of ERP integrations with third party Information Systems (IS, the lack of mechanisms for monitoring BP instances, backward recovery, user notification about the current state and tasks, and inability to make explicit changes in customers’ ISs.

  7. Využití databázových systémů v sw balících typu ERP/ERP II

    OpenAIRE

    Vašek, Martin

    2010-01-01

    This thesis is concerning with problems of using database systems in ERP / ERP II software packages. The goal is to define position of ERP / ERP II systems in the Information System market. With this topic are also connected characteristics of database systems and definition of their specific position towards ERP / ERP II solutions. Except classical solutions, when the whole Information System is situated "inside" a company, there are also analyzed new attitudes, which respect external provid...

  8. Interpreting an ERP implementation from a stakeholder perspective

    NARCIS (Netherlands)

    Boonstra, A.

    2005-01-01

    ERP systems are software packages that enable the integration of transactions oriented data and business processes throughout an organization. ERP implementation can be viewed as an organizational change process: many problems related to ERP implementation are related to a misfit of the system with

  9. ANALISIS FAKTOR PENDORONG REALISASI MANFAAT IMPLEMENTASI ERP DI PERUSAHAAN INDONESIA

    OpenAIRE

    Iqbal Yulizar M.; Rajesri Govindaraju

    2017-01-01

    Pengelolaan implementasi ERP pada fase post project yaitu fase ketika ERP telah digunakan secara integral dalam perusahaan, menentukan terealisasinya manfaat dari implementasi ERP, karenanya terkait pengelolaan pada fase post project ini dibutuhkan kajian lebih lanjut untuk mengetahui upaya-upaya merealisasikan manfaat dari implementasi ERP. Penelitian ini bertujuan untuk mengetahui bagaimana mengukur manfaat implementasi ERP dan mengetahui sejauh mana perusahaan-perusahaan Indonesia merealis...

  10. Developing a cultural perspective on ERP

    NARCIS (Netherlands)

    Boersma, F.K.; Kingma, S.F.

    2005-01-01

    Purpose - To develop an analytical framework through which the organizational cultural dimension of enterprise resource planning (ERP) implementations can be analyzed. Design/methodology/approach - This paper is primarily based on a review of the literature. Findings - ERP is an enterprise system

  11. Connexin Communication Compartments and Wound Repair in Epithelial Tissue

    Directory of Open Access Journals (Sweden)

    Marc Chanson

    2018-05-01

    Full Text Available Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems.

  12. Dynamic changes in connexin expression following engraftment of neural stem cells to striatal tissue

    International Nuclear Information System (INIS)

    Jaederstad, Johan; Jaederstad, Linda Maria; Herlenius, Eric

    2011-01-01

    Gap-junctional intercellular communication between grafted neural stem cells (NSCs) and host cells seem to be essential for many of the beneficial effects associated with NSC engraftment. Utilizing murine NSCs (mNSCs) grafted into an organotypic ex vivo model system for striatal tissue we examined the prerequisites for formation of gap-junctional couplings between graft and host cells at different time points following implantation. We utilized flow cytometry (to quantify the proportion of connexin (Cx) 26 and 43 expressing cells), immunohistochemistry (for localization of the gap-junctional proteins in graft and host cells), dye-transfer studies with and without pharmacological gap-junctional blockers (assaying the functionality of the formed gap-junctional couplings), and proliferation assays (to estimate the role of gap junctions for NSC well-being) to this end. Immunohistochemical staining and dye-transfer studies revealed that the NSCs already form functional gap junctions prior to engraftment, thereby creating a substrate for subsequent graft and host communication. The expression of Cx43 by grafted NSCs was decreased by neurotrophin-3 overexpression in NSCs and culturing of grafted tissue in serum-free Neurobasal B27 medium. Cx43 expression in NSC-derived cells also changed significantly following engraftment. In host cells the expression of Cx43 peaked following traumatic stimulation and then declined within two weeks, suggesting a window of opportunity for successful host cell rescue by NSC engraftment. Further investigation of the dynamic changes in gap junction expression in graft and host cells and the associated variations in intercellular communication between implanted and endogenous cells might help to understand and control the early positive and negative effects evident following neural stem cell transplantation and thereby optimize the outcome of future clinical NSC transplantation therapies.

  13. Intracellular trafficking pathways of Cx43 gap junction channels.

    Science.gov (United States)

    Epifantseva, Irina; Shaw, Robin M

    2018-01-01

    Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling. Impairment in gap junction trafficking contributes to dangerous complications in diseased hearts such as the arrhythmias of sudden cardiac death. Of recent interest are the protein-protein interactions with the Cx43 carboxy-terminus. These interactions have significant impact on the full length Cx43 lifecycle and also contribute to trafficking of Cx43 as well as possibly other functions. We are learning that many of the known non-canonical roles of Cx43 can be attributed to the recently identified six endogenous Cx43 truncated isoforms which are produced by internal translation. In general, alternative translation is a new leading edge for proteome expansion and therapeutic drug development. This review highlights recent mechanisms identified in the trafficking of gap junction channels, involvement of other proteins contributing to the delivery of channels to the cell-cell border, and understanding of possible roles of the newly discovered alternatively translated isoforms in Cx43 biology. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Trust at first sight: evidence from ERPs.

    Science.gov (United States)

    Marzi, Tessa; Righi, Stefania; Ottonello, Sara; Cincotta, Massimo; Viggiano, Maria Pia

    2014-01-01

    We used event-related potentials (ERPs) to tap the temporal dynamics of first impressions based on face appearance. Participants were asked to evaluate briefly presented faces for trustworthiness and political choice. Behaviorally, participants were better at discriminating faces that were pre-rated as untrustworthy. The ERP results showed that the P100 component was enhanced for untrustworthy faces, consistently with the view that signals of potential threat are given precedence in neural processing. The enhanced ERP responses to untrustworthy faces persisted throughout the processing sequence and the amplitude of early posterior negativity (EPN), and subsequent late positive potential (LPP) was increased with respect to trustworthy faces which, in contrast, elicited an enhanced positivity around 150 ms on frontal sites. These ERP patterns were found specifically for the trustworthiness evaluation and not for the political decision task. Political decision yielded an increase in the N170 amplitude, reflecting a more demanding and taxing structural encoding. Similar ERP responses, as previously reported in the literature for facial expressions processing, were found throughout the entire time course specifically elicited by faces explicitly judged as untrustworthy. One possibility might be that evolution has provided the brain with a 'special toolkit' for trust evaluation that is fast and triggers ERPs related to emotional processing.

  15. A graphical user interface for infant ERP analysis.

    Science.gov (United States)

    Kaatiala, Jussi; Yrttiaho, Santeri; Forssman, Linda; Perdue, Katherine; Leppänen, Jukka

    2014-09-01

    Recording of event-related potentials (ERPs) is one of the best-suited technologies for examining brain function in human infants. Yet the existing software packages are not optimized for the unique requirements of analyzing artifact-prone ERP data from infants. We developed a new graphical user interface that enables an efficient implementation of a two-stage approach to the analysis of infant ERPs. In the first stage, video records of infant behavior are synchronized with ERPs at the level of individual trials to reject epochs with noncompliant behavior and other artifacts. In the second stage, the interface calls MATLAB and EEGLAB (Delorme & Makeig, Journal of Neuroscience Methods 134(1):9-21, 2004) functions for further preprocessing of the ERP signal itself (i.e., filtering, artifact removal, interpolation, and rereferencing). Finally, methods are included for data visualization and analysis by using bootstrapped group averages. Analyses of simulated and real EEG data demonstrated that the proposed approach can be effectively used to establish task compliance, remove various types of artifacts, and perform representative visualizations and statistical comparisons of ERPs. The interface is available for download from http://www.uta.fi/med/icl/methods/eeg.html in a format that is widely applicable to ERP studies with special populations and open for further editing by users.

  16. Progressive quality control of secretory proteins in the early secretory compartment by ERp44.

    Science.gov (United States)

    Sannino, Sara; Anelli, Tiziana; Cortini, Margherita; Masui, Shoji; Degano, Massimo; Fagioli, Claudio; Inaba, Kenji; Sitia, Roberto

    2014-10-01

    ERp44 is a pH-regulated chaperone of the secretory pathway. In the acidic milieu of the Golgi, its C-terminal tail changes conformation, simultaneously exposing the substrate-binding site for cargo capture and the RDEL motif for ER retrieval through interactions with cognate receptors. Protonation of cysteine 29 in the active site allows tail movements in vitro and in vivo. Here, we show that conserved histidine residues in the C-terminal tail also regulate ERp44 in vivo. Mutants lacking these histidine residues retain substrates more efficiently. Surprisingly, they are also O-glycosylated and partially secreted. Co-expression of client proteins prevents secretion of the histidine mutants, forcing tail opening and RDEL accessibility. Client-induced RDEL exposure allows retrieval of proteins from distinct stations along the secretory pathway, as indicated by the changes in O-glycosylation patterns upon overexpression of different partners. The ensuing gradients might help to optimize folding and assembly of different cargoes. Endogenous ERp44 is O-glycosylated and secreted by human primary endometrial cells, suggesting possible pathophysiological roles of these processes. © 2014. Published by The Company of Biologists Ltd.

  17. The disulfide isomerase ERp57 is required for fibrin deposition in vivo.

    Science.gov (United States)

    Zhou, J; Wu, Y; Wang, L; Rauova, L; Hayes, V M; Poncz, M; Essex, D W

    2014-11-01

    ERp57 is required for platelet function; however, whether ERp57 contributes to fibrin generation is unknown. Using an inhibitory anti-ERp57 antibody (mAb1), Pf4-Cre/ERp57(fl/fl) mice, Tie2-Cre/ERp57(fl/fl) mice, and mutants of ERp57, we analyzed the function of ERp57 in laser-induced thrombosis. Fibrin deposition was decreased in Pf4-Cre/ERp57(fl/fl) mice, consistent with a role for platelet ERp57 in fibrin generation. Fibrin deposition was further decreased with infusion of mAb1 and in Tie2-Cre/ERp57(fl/fl) mice, consistent with endothelial cells also contributing to fibrin deposition. Infusion of eptibifatide inhibited platelet and fibrin deposition, confirming a role for platelets in fibrin deposition. Infusion of recombinant ERp57 corrected the defect in fibrin deposition but not platelet accumulation, suggesting a direct effect of ERp57 on coagulation. mAb1 inhibited thrombin generation in vitro, consistent with a requirement for ERp57 in coagulation. Platelet accumulation was decreased to similar extents in Pf4-Cre/ERp57(fl/fl) mice, Tie2-Cre/ERp57(fl/fl) mice and normal mice infused with mAb1. Infusion of completely inactivated ERp57 or ERp57 with a non-functional second active site inhibited fibrin deposition and platelet accumulation, indicating that the isomerase activity of the second active site is required for these processes. ERp57 regulates thrombosis via multiple targets. © 2014 International Society on Thrombosis and Haemostasis.

  18. How little do we need to know about Enterprise Resource Planning (ERP)? - A critical review of information systems research on ERP

    DEFF Research Database (Denmark)

    Koch, Christian; Olsen, Martin; Tambo, Torben

    2010-01-01

    ERP. It is discussed whether sociomaterial, actornetwork approaches can deliver another and richer analysis or whether a dual paradigmatic approach, combining a content analysis on the technical side, based on a systems theory approach, with a sociological approach to the social side, would...... aside in the IS-research on ERP: the technological content and the time dynamics.Using two different small reviews of journal articles from IS journals in 2004 and 2010 it is showed how IS research on ERP delivers strong insight in social processes and conditions around ERP, but largely disregards...

  19. Adoption of ERP system: An empirical study of factors influencing the usage of ERP and its impact on end user

    Directory of Open Access Journals (Sweden)

    Christy Angeline Rajan

    2015-06-01

    Full Text Available Complex information systems like the ERP integrate the data of all business areas within the organization. The implementation of ERP is a difficult process as it involves different types of end users. Based on literature, we proposed a conceptual framework and examined it to find the effect of some of the individual, organizational, and technological factors on the usage of ERP and its impact on the end user. The results of the analysis suggest that computer self-efficacy, organizational support, training, and compatibility have a positive influence on ERP usage which in turn has significant influence on panoptic empowerment and individual performance.

  20. ERP systems selection in multinational enterprises: a practical guide

    Directory of Open Access Journals (Sweden)

    Moutaz Haddara

    2018-01-01

    Full Text Available The Enterprise Resource Planning (ERP system selection is an early phase in the ERP adoption process. When organizations evaluate an ERP, they commonly develop their own selection criteria that usually involve various system and vendor related factors. While the selection process is critical, however, there is an apparent research gap in literature. The ERP selection effort also focuses on the system’s fit with the organizational requirements and needs. Thus, the selection phase is critical, because if an organization chooses an unfit ERP, the whole project could be predestined to fail. This research provides an overview of an ERP selection process at an overseas branch office of a multinational company. The process employed a simple multi-attribute rating technique (SMART for evaluation. In addition, this research presents how cross-border data protection laws between the parent company and its branch have influenced the selection process. As the ERP system has been implemented successfully, the method and the selection factors have been proven adequate for the selection process.

  1. Disruption of gap junctional intercellular communication by antibiotic gentamicin is associated with aberrant localization of occludin, N-cadherin, connexin 43, and vimentin in SerW3 Sertoli cells in vitro.

    Science.gov (United States)

    Bekheet, Souad H M; Stahlmann, Ralf

    2009-09-01

    Spermatogenesis is a very complex process by which male germ cells differentiate into mature spermatozoa. The sophisticated communication network that controls spermatogenesis can be derailed so that dysfunction of one cell type propagates to all types as a cascade. This accounts for the particular vulnerability of the testis to environmental factors such as drugs and xenobiotics. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. In this study, cells from the rat Sertoli line (SerW3) were incubated for 3, 6 and 9 subsequent days in serum free DMEM (SFDM) composed of DMEM supplemented with three different concentrations of antibiotic gentamicin (10, 30, and 100 μg). The effect of the three different concentrations of this antibiotic was determined on Sertoli cell-cell interaction through impaired expression of their constitutive tight junction proteins as early targets for different toxicants in vitro by immunochemistry analysis. The Sertoli SerW3 cell line illustrated the cytotoxicity of GS, as the intercellular junction proteins such as occludin, N-cadherin, connexin 43, and vimentin were delocalized from the membrane to the cytoplasmic compartment during exposure to the antibiotic. This study underlines the potential deleterious effects of the routine use of antibiotics during continuous cell culture.

  2. 25 CFR 213.43 - Relinquishment of Government supervision.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Relinquishment of Government supervision. 213.43 Section 213.43 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING Removal of Restrictions § 213.43 Relinquishment of Government supervision....

  3. EEG frequency PCA in EEG-ERP dynamics.

    Science.gov (United States)

    Barry, Robert J; De Blasio, Frances M

    2018-05-01

    Principal components analysis (PCA) has long been used to decompose the ERP into components, and these mathematical entities are increasingly accepted as meaningful and useful representatives of the electrophysiological components constituting the ERP. A similar expansion appears to be beginning in regard to decomposition of the EEG amplitude spectrum into frequency components via frequency PCA. However, to date, there has been no exploration of the brain's dynamic EEG-ERP linkages using PCA decomposition to assess components in each measure. Here, we recorded intrinsic EEG in both eyes-closed and eyes-open resting conditions, followed by an equiprobable go/no-go task. Frequency PCA of the EEG, including the nontask resting and within-task prestimulus periods, found seven frequency components within the delta to beta range. These differentially predicted PCA-derived go and no-go N1 and P3 ERP components. This demonstration suggests that it may be beneficial in future brain dynamics studies to implement PCA for the derivation of data-driven components from both the ERP and EEG. © 2017 Society for Psychophysiological Research.

  4. Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states.

    Science.gov (United States)

    Bargiello, Thaddeus A; Oh, Seunghoon; Tang, Qingxiu; Bargiello, Nicholas K; Dowd, Terry L; Kwon, Taekyung

    2018-01-01

    Voltage is an important physiologic regulator of channels formed by the connexin gene family. Connexins are unique among ion channels in that both plasma membrane inserted hemichannels (undocked hemichannels) and intercellular channels (aggregates of which form gap junctions) have important physiological roles. The hemichannel is the fundamental unit of gap junction voltage-gating. Each hemichannel displays two distinct voltage-gating mechanisms that are primarily sensitive to a voltage gradient formed along the length of the channel pore (the transjunctional voltage) rather than sensitivity to the absolute membrane potential (V m or V i-o ). These transjunctional voltage dependent processes have been termed V j - or fast-gating and loop- or slow-gating. Understanding the mechanism of voltage-gating, defined as the sequence of voltage-driven transitions that connect open and closed states, first and foremost requires atomic resolution models of the end states. Although ion channels formed by connexins were among the first to be characterized structurally by electron microscopy and x-ray diffraction in the early 1980's, subsequent progress has been slow. Much of the current understanding of the structure-function relations of connexin channels is based on two crystal structures of Cx26 gap junction channels. Refinement of crystal structure by all-atom molecular dynamics and incorporation of charge changing protein modifications has resulted in an atomic model of the open state that arguably corresponds to the physiologic open state. Obtaining validated atomic models of voltage-dependent closed states is more challenging, as there are currently no methods to solve protein structure while a stable voltage gradient is applied across the length of an oriented channel. It is widely believed that the best approach to solve the atomic structure of a voltage-gated closed ion channel is to apply different but complementary experimental and computational methods and to use

  5. ERP systems selection in multinational enterprises: a practical guide

    OpenAIRE

    Moutaz Haddara

    2018-01-01

    The Enterprise Resource Planning (ERP) system selection is an early phase in the ERP adoption process. When organizations evaluate an ERP, they commonly develop their own selection criteria that usually involve various system and vendor related factors. While the selection process is critical, however, there is an apparent research gap in literature. The ERP selection effort also focuses on the system’s fit with the organizational requirements and needs. Thus, the selection phase is critical,...

  6. A Study of Successful ERP – From the Organization Fit Perspective

    Directory of Open Access Journals (Sweden)

    Huei-Huang Chen

    2009-08-01

    Full Text Available Many enterprises implemented Enterprise Resource Planning (ERP systems as a bedrock strategy with a view to integrating all data and bringing an organization into a joint system. However, most enterprises in an attempt to carry out ERP often end up in failure and it seems the probability of the mishaps is considerably high. This paper applies the Organization Fit Theory to examine an organization characters and features beforehand can present a clearer picture for the ERP designers. This paper is to sort out key variables in Organization Fit corresponding to successful ERP cases. Questionnaires are sent through conventional postal means and electronic networks. Its samplings include top 500 enterprises in Taiwan with data regarding successful working experience of ERP as well as impacts on the ERP process as a result of the related variables. The research result shows that organizational fit of ERP has a positive influence on implementation success. The research result also shows that none of ERP adaptation, process adaptation, and organizational resistance has any moderating effect on organizational fit of ERP and ERP implementation success.

  7. CAPABILITIES AND ACTORS IN ERP SYSTEMS MANAGEMENT: AN EXPLORATORY STUDY IN CORPORATE USERS OF SAP ERP

    Directory of Open Access Journals (Sweden)

    Ronaldo Zwicker

    2007-10-01

    Full Text Available ERP systems are now an important component of information technology architecture in most large and medium sized companies. As such, it is inevitable that the activities undertaken to align this component to business requirements, conduct its evolution and ensure its performance and availability become increasingly important to companies’ IT areas. Success of these activities relies upon knowledge and participation of various actors inside and outside the IT area, imposing challenges not observed in internally developed systems. This paper proposes a model for the analysis of ERP systems management based on a previous work on the subject with the inclusion of the IT capabilities model and a description of the actors (stakeholders involved in the process of using an ERP system in a company. The proposed model is the basis for an exploratory survey conducted with 85 Brazilian companies whose results also comprise this text. The results suggest that only part of the capabilities is present and only part of the actors effectively participates on the ERP systems management effort.

  8. Challenges and Success Factors of ERP Systems in Australian SMEs

    Directory of Open Access Journals (Sweden)

    Sitalakshmi Venkatraman

    2016-05-01

    Full Text Available Today, great potential is envisaged for ERP systems in small and medium-sized enterprises (SMEs, and software vendors have been repackaging their ERP systems for SMEs with a recent focus on cloud-based systems. While cloud ERP offers the best solution for SMEs without the overheads of the huge investment and management costs that are associated with traditional ERP systems, the SME sector faces many challenges in their adoption. Traditional ERP studies have predominantly focused on large organizations, and gaps in the literature indicate that both vendor and consumer perspectives require more understanding with new technology offerings for SMEs. This paper describes some of the common challenges, such as cost effectiveness, alignment between software and business processes, customized governance and training, which form the major SME constraints for ERP system adoption. Due to the dynamic nature of SME businesses, best practice guidelines for an SME’s ERP implementation could be arrived at through closer investigation of its business requirements in order to avoid misfits. This forms the main objective of the study. We identify key success factors of ERP implementation in an Australian SME as a case study. These target success factors are then compared to the actual outcomes achieved. Factors such as business process alignment with the ERP system, meeting customer and stakeholder needs and reducing recurring and maintenance costs were key to the success of ERP implementation for the Australian SME. In particular, the IT and business strategy alignment with a customer focus and flexible reporting features of ERP systems has resulted in business agility.

  9. Connexin 50 Mutation Lowers Blood Pressure in Spontaneously Hypertensive Rat

    Czech Academy of Sciences Publication Activity Database

    Šeda, Ondřej; Liška, F.; Pravenec, Michal; Vernerová, Z.; Kazdová, L.; Křenová, D.; Zídek, Václav; Šedová, Lucie; Krupková, M.; Křen, V.

    2017-01-01

    Roč. 66, č. 1 (2017), s. 15-28 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:68378050 ; RVO:67985823 Keywords : Connexin * Hypertension * Transcriptome * Animal models * Insulin resistance Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (FGU-C) Impact factor: 1.461, year: 2016

  10. ERP services effort estimation strategies based on early requirements

    NARCIS (Netherlands)

    Erasmus, I.P.; Daneva, Maia; Kalenborg, Axel; Trapp, Marcus

    2015-01-01

    ERP clients and vendors necessarily estimate their project interventions at a very early stage, before the full requirements to an ERP solution are known and often before a contract is finalized between a vendor/ consulting company and a client. ERP project estimation at the stage of early

  11. Business Management Software Axolon ERP

    OpenAIRE

    Axolon ERP Solution

    2018-01-01

    Axolon ERP a Business Management Software www.axolonerp.com by Micromind is a comprehensive business management software solution for businesses. We deliver Business Management Software Dubai in UAE, GCC Countries and products also include ERP Software Dubai. HR & Payroll, Inventory Software, Project Management, Software Development, Solutions and Services in Dubai, UAE for small and medium sized Enterprises (SME) in the middle east with a easy-to-use, secure and efficient business management...

  12. ERP correlates of German Sign Language processing in deaf native signers.

    Science.gov (United States)

    Hänel-Faulhaber, Barbara; Skotara, Nils; Kügow, Monique; Salden, Uta; Bottari, Davide; Röder, Brigitte

    2014-05-10

    The present study investigated the neural correlates of sign language processing of Deaf people who had learned German Sign Language (Deutsche Gebärdensprache, DGS) from their Deaf parents as their first language. Correct and incorrect signed sentences were presented sign by sign on a computer screen. At the end of each sentence the participants had to judge whether or not the sentence was an appropriate DGS sentence. Two types of violations were introduced: (1) semantically incorrect sentences containing a selectional restriction violation (implausible object); (2) morphosyntactically incorrect sentences containing a verb that was incorrectly inflected (i.e., incorrect direction of movement). Event-related brain potentials (ERPs) were recorded from 74 scalp electrodes. Semantic violations (implausible signs) elicited an N400 effect followed by a positivity. Sentences with a morphosyntactic violation (verb agreement violation) elicited a negativity followed by a broad centro-parietal positivity. ERP correlates of semantic and morphosyntactic aspects of DGS clearly differed from each other and showed a number of similarities with those observed in other signed and oral languages. These data suggest a similar functional organization of signed and oral languages despite the visual-spacial modality of sign language.

  13. The Implications of Real Options on ERP-Enabled Adoption

    Science.gov (United States)

    Nwankpa, Joseph K.

    2012-01-01

    Current research on Enterprise Resource Planning (ERP) systems and real options focuses on valuation and justification issues that manager's face prior to project approval with existing literature attempting to demonstrate that ERP systems as technology positioning investments have option-like characteristics thus making such ERP systems…

  14. TAM-based external factors related to ERP solutions acceptance in organizations

    Directory of Open Access Journals (Sweden)

    Simona Zabukovsek

    2013-01-01

    Full Text Available To improve the efficiency and effectiveness of ERP solutions use, understanding of critical success factors of ERP solutions assimilation in organizations is crucial. The technology acceptance model (TAM proposed by Davis (1989 has been the most widely used model for researching user acceptance and usage of IT/IS. The purpose of this paper is to extend the original TAM with groups of external factors which impact actual ERP system use. First, we focus on ERP system use in companies’ maturity phase. Second, we expose and examine three groups of external factors which influence ERP usage. The model was empirically tested using data collected from a survey of ERP users in 44 organizations. Survey data have been collected from ERP users who have been exposed to an ERP system which has operated for more than one year. The proposed research model was analyzed using the PLS approach.

  15. ERP sistēmas ieviešana

    OpenAIRE

    Proskurins, Aleksandrs

    2008-01-01

    Šajā darbā tika apskatīta informācijas sistēmu klasifikācija, uzņēmuma resursu plānošanas sistēmas (ERP) definīcija un tās vieta IS klasifikācijā. Tika apskatīti ERP sistēmu ieviešanas teorētiskie aspekti, izstrādes un pielāgošanas specifika, kā arī tika izanalizēti vairāki ERP sistēmas ieviešanas projekti Latvijas uzņēmumos.

  16. Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.

    Science.gov (United States)

    Nisbet, Ashley M; Camelliti, Patrizia; Walker, Nicola L; Burton, Francis L; Cobbe, Stuart M; Kohl, Peter; Smith, Godfrey L

    2016-05-01

    Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. CEO Interests and Concerns in Second Wave ERP

    DEFF Research Database (Denmark)

    Simonsen, Martin Lyngaa; Nielsen, Esben Toftdahl; Kræmmergaard, Pernille

    2006-01-01

    This paper is the product of a study of what top management find interesting and what is of concern to them in relation to the Enterprise Resource Planning (ERP) systems in the second wave of ERP. Very little empirical research exists on the subject of the interests and concerns of CEOs in relation...... to a company's ERP System. However research into information system literature indicates that CEOs are valued as key players in the management of IT to secure that the IT strategy is aligned with the business strategy. Based on the fact that very little prior research exists on the CEOs' interests and concerns...... in relation to the ERP system in the second wave, we employed an interpretive explorative case study with a grounded approach carried out through open interviews with CEOs. The research was conducted in three mid-size Danish production companies all of which have an ERP system. The contribution of this paper...

  18. Regulation of connexins expression levels by microRNAs, an update

    Directory of Open Access Journals (Sweden)

    Juan Francisco Calderon

    2016-11-01

    Full Text Available Control of cell-cell coordination and communication is regulated by several factors, including paracrine and autocrine release of biomolecules, and direct exchange of soluble factors between cells through gap junction channels. Additionally, hemichannels also participate in cell-cell coordination through the release of signaling molecules, such as ATP and glutamate. A family of transmembrane proteins named connexins forms both gap junction channels and hemichannels. Because of their importance in cell and tissue coordination, connexins are controlled both by post-translational and post-transcriptional modifications. In recent years, non-coding RNAs have garnered research interest due to their ability to exert post-transcriptional regulation of gene expression. One of the most recent, well-documented control mechanisms of protein synthesis is found through the action of small, single-stranded RNA, called micro RNAs (miRNAs or miRs. Put simply, miRNAs are negative regulators of the expression of a myriad proteins involved in many physiological and pathological processes. This mini review will briefly summarize what is currently known about the action of miRNAs over Cxs expression/function in different organs under some relevant physiological and pathological conditions

  19. Training and testing ERP-BCIs under different mental workload conditions

    Science.gov (United States)

    Ke, Yufeng; Wang, Peiyuan; Chen, Yuqian; Gu, Bin; Qi, Hongzhi; Zhou, Peng; Ming, Dong

    2016-02-01

    Objective. As one of the most popular and extensively studied paradigms of brain-computer interfaces (BCIs), event-related potential-based BCIs (ERP-BCIs) are usually built and tested in ideal laboratory settings in most existing studies, with subjects concentrating on stimuli and intentionally avoiding possible distractors. This study is aimed at examining the effect of simultaneous mental activities on ERP-BCIs by manipulating various levels of mental workload during the training and/or testing of an ERP-BCI. Approach. Mental workload was manipulated during the training or testing of a row-column P300-speller to investigate how and to what extent the spelling performance and the ERPs evoked by the oddball stimuli are affected by simultaneous mental workload. Main results. Responses of certain ERP components, temporal-occipital N200 and the late reorienting negativity evoked by the oddball stimuli and the classifiability of ERP features between targets and non-targets decreased with the increase of mental workload encountered by the subject. However, the effect of mental workload on the performance of ERP-BCI was not always negative but depended on the conditions where the ERP-BCI was built and applied. The performance of ERP-BCI built under an ideal lab setting without any irrelevant mental activities declined with the increasing mental workload of the testing data. However, the performance was significantly improved when an ERP-BCI was built under an appropriate mental workload level, compared to that built under speller-only conditions. Significance. The adverse effect of concurrent mental activities may present a challenge for ERP-BCIs trained in ideal lab settings but which are to be used in daily work, especially when users are performing demanding mental processing. On the other hand, the positive effects of the mental workload of the training data suggest that introducing appropriate mental workload during training ERP-BCIs is of potential benefit to the

  20. Organization Readiness and ERP Implementation in Albaha University

    Science.gov (United States)

    Alaqeel, K.; Shakkah, M. S.; Rahmat, R. F.; Alfageeh, A.; Budiarto, R.

    2017-04-01

    This work studies the correlation between the organizational readiness in Albaha University and the respective Critical Success Factors with regards to the Enterprise Resource Planning (ERP) implementation. The study also considers some suggestions to improve the ABU’s ERP systems and roadmap towards the self -development strategy and to reduce vendor-dependency. A survey regarding ERP to the end-users, experts and developers in Albaha University was conducted. The analysis of the results in this work confirmed with the results of an existing work. The four significance success factors: Project Management, Business Process Re-engineering, System Integration, and Training and Education are recommended to be adopted to assure the smooth adoption of ERP at Albaha University.

  1. Connexin domains relevant to the chemical gating of gap junction channels

    Directory of Open Access Journals (Sweden)

    C. Peracchia

    1997-05-01

    Full Text Available Most cells exchange ions and small metabolites via gap junction channels. These channels are made of two hemichannels (connexons, each formed by the radial arrangement of six connexin (Cx proteins. Connexins span the bilayer four times (M1-M4 and have both amino- and carboxy-termini (NT, CT at the cytoplasmic side of the membrane, forming two extracellular loops (E1, E2 and one inner (IL loop. The channels are regulated by gates that close with cytosolic acidification (e.g., CO2 treatment or increased calcium concentration, possibly via calmodulin activation. Although gap junction regulation is still unclear, connexin domains involved in gating are being defined. We have recently focused on the CO2 gating sensitivity of Cx32, Cx38 and various mutants and chimeras expressed in Xenopus oocytes and studied by double voltage clamp. Cx32 is weakly sensitive to CO2, whereas Cx38 is highly sensitive. A Cx32 chimera containing the second half of the inner loop (IL2 of Cx38 was as sensitive to CO2 as Cx38, indicating that this domain plays an important role. Deletion of CT by 84% did not affect CO2 sensitivity, but replacement of 5 arginines (R with sparagines (N at the beginning of CT (C1 greatly enhanced the CO2 sensitivity of Cx32. This suggests that whereas most of CT is irrelevant, positive charges of C1 maintain the CO2 sensitivity of Cx32 low. As a hypothesis we have proposed a model that involves charge interaction between negative residues of the beginning of IL1 and positive residues of either C1 or IL2. Open and closed channels would result from IL1-C1 and IL1-IL2 interactions, respectively

  2. A Fuzzy-MOORA approach for ERP system selection

    Directory of Open Access Journals (Sweden)

    Prasad Karande

    2012-07-01

    Full Text Available In today’s global and dynamic business environment, manufacturing organizations face the tremendous challenge of expanding markets and meeting the customer expectations. It compels them to lower total cost in the entire supply chain, shorten throughput time, reduce inventory, expand product choice, provide more reliable delivery dates and better customer service, improve quality, and efficiently coordinate demand, supply and production. In order to accomplish these objectives, the manufacturing organizations are turning to enterprise resource planning (ERP system, which is an enterprise-wide information system to interlace all the necessary business functions, such as product planning, purchasing, inventory control, sales, financial and human resources into a single system having a shared database. Thus to survive in the global competitive environment, implementation of a suitable ERP system is mandatory. However, selecting a wrong ERP system may adversely affect the manufacturing organization’s overall performance. Due to limitations in available resources, complexity of ERP systems and diversity of alternatives, it is often difficult for a manufacturing organization to select and install the most suitable ERP system. In this paper, two ERP system selection problems are solved using fuzzy multi-objective optimization on the basis of ratio analysis (MOORA method and it is observed that in both the cases, SAP is the best solution.

  3. Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure.

    Science.gov (United States)

    Beyer, Eric C; Lipkind, Gregory M; Kyle, John W; Berthoud, Viviana M

    2012-08-01

    The amino terminal domain (NT) of the connexins consists of their first 22-23 amino acids. Site-directed mutagenesis studies have demonstrated that NT amino acids are determinants of gap junction channel properties including unitary conductance, permeability/selectivity, and gating in response to transjunctional voltage. The importance of this region has also been emphasized by the identification of multiple disease-associated connexin mutants affecting amino acid residues in the NT region. The first part of the NT is α-helical. The structure of the Cx26 gap junction channel shows that the NT α-helix localizes within the channel, and lines the wall of the pore. Interactions of the amino acid residues in the NT with those in the transmembrane helices may be critical for holding the channel open. The predicted sites of these interactions and the applicability of the Cx26 structure to the NT of other connexins are considered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. Copyright © 2011. Published by Elsevier B.V.

  4. A Comprehensive, Competency-Based Education Framework Using Medium-Sized ERP Systems

    Science.gov (United States)

    Scholtz, Brenda; Cilliers, Charmain; Calitz, Andre

    2012-01-01

    Graduates with industry-relevant ERP competencies are highly sought after. This requirement is due to a dominance of Enterprise Resource Planning (ERP) systems and the positive affect which good quality ERP specialists have on the success rate of ERP system implementation projects. Universities are therefore increasingly pressurised to supply…

  5. Personalized Training in Romanian SME’s ERP Implementation Projects

    Directory of Open Access Journals (Sweden)

    Iuliana DOROBAT

    2010-01-01

    Full Text Available Many practitioners and IS researchers have stated that the overwhelming majority of Enter-prise Resource Planning (ERP systems implementations exceed their training budget and their time allocations. In consequence many Romanian SMEs that implement an ERP system are looking to new approaches of knowledge transfer and performance support that are better aligned with business goals, deliver measurable results and are cost effective. Thus, we have begun to analyze the training methods used in ERP implementation in order to provide a so-lution that could help us maximize the efficiency of an ERP training program. We proposed a framework of an ERPTraining module that can be integrated with a Romanian ERP system and which provides a training management that is more personalized, effective and less ex-pensive.

  6. ERP implementations and their impact upon management accountants

    OpenAIRE

    Sangster, Alan; Leech, Stewart A.; Grabski, Severin

    2009-01-01

    This paper considers the impact of ERP implementations upon the role of management accountants, upon management accounting in general, and upon business processes. It does so in the context of the perceived success of the ERP implementation. A postal questionnaire was circulated to almost 700 management accountants working in large UK-based organisations. It finds that under successful ERP implementations, management accountants have time for other, less mundane activities and their role beco...

  7. A Framework for ERP Post-Implementation Amendments: A Literature Analysis

    Directory of Open Access Journals (Sweden)

    Taiwo Oseni

    2017-06-01

    Full Text Available Post-implementation amendments to ERP systems (ERP-PIA are of importance for advancing ERP research, but more importantly essential if ERP systems are to be used as a strategic and competitive business tool. For ease of clarity, we have adopted the term “amendments” to encompass the main forms of post implementation activities: maintenance, enhancements and upgrades. The term ‘amendments’ is used to counteract one of the major findings from this research - the inconsistency of terms used by many authors to explain post implementation activities. This paper presents a review of the ERP post-implementation amendment literature in order to provide answers to two specific questions: first, what is the current state of research in the field of ERP-PIA; and second, what are the future research directions that need to be explored in the field of ERP-PIA. From the review, we develop a framework to identify: (a major themes concerning ERP post-implementation amendments, (b inherent gaps in the post-implementation amendments literature, and (c specific areas that require further research attention influencing the uptake of amendments. Suggestions on empirical evaluation of research directions and their relevance in the extension of existing literature is presented.

  8. Factors influencing ERP implementation in Indian SMEs: An empirical analysis

    Directory of Open Access Journals (Sweden)

    Rana Basu

    2011-04-01

    Full Text Available Enterprise Resource Planning (ERP is essentially a commercial software package that enables the integration of transaction - oriented data and business processes throughout an organization. In order to remain competitive in this global business scenario, the small and medium scale enterprises (SMEs are opting for ERP implementation. In Indian SME sector, the adoption of ERP is rapidly increasing. Literature shows many instances where organizations, even after implementing such novel information systems like ERP, are unable to derive the benefits of integration. It is, therefore, not surprising that implementation of enterprise information systems in general is quite difficult due to their size, scope and complexity. Therefore, there is a need to identify some issues that would lead to positive outcome for the implementation of ERP systems in the context of Indian SME sector. This paper thus attempts to identify and to prioritize the factors influencing proper implementation of ERP systems in a business organization particularly for Indian small and medium businesses (SMBs. The research presented here is specifically targeted the Indian SMEs, which have already completed the process of implementing ERP system.

  9. PROBLEM OF CHOICE ERP-SYSTEM

    Directory of Open Access Journals (Sweden)

    Anna A. Varshavskaya

    2013-01-01

    Full Text Available The article describes the criteria for selecting the ERP-system and groups of risk of such systems. The descriptions of the leaders of the Russian market of ERP-systems, which have shown good results over the years of its existence in Russia, are given. The solution of such problem is a synthesis of the views of their own and third-party experts. A company will be glad with the system, if it is chosen in such way.

  10. Mechanism for modulation of gating of connexin26-containing channels by taurine

    Science.gov (United States)

    Kieken, Fabien; Tao, Liang; Sorgen, Paul L.; Harris, Andrew L.

    2011-01-01

    The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28–amino acid “tag” to the carboxyl-terminal domain (CT) of Cx26 (Cx26T) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26Tc) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26Tc/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32T and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function. PMID:21844220

  11. A cataract-causing connexin 50 mutant is mislocalized to the ER due to loss of the fourth transmembrane domain and cytoplasmic domain.

    Science.gov (United States)

    Somaraju Chalasani, Madhavi Latha; Muppirala, Madhavi; G Ponnam, Surya Prakash; Kannabiran, Chitra; Swarup, Ghanshyam

    2013-01-01

    Mutations in the eye lens gap junction protein connexin 50 cause cataract. Earlier we identified a frameshift mutant of connexin 50 (c.670insA; p.Thr203AsnfsX47) in a family with autosomal recessive cataract. The mutant protein is smaller and contains 46 aberrant amino acids at the C-terminus after amino acid 202. Here, we have analysed this frameshift mutant and observed that it localized to the endoplasmic reticulum (ER) but not in the plasma membrane. Moreover, overexpression of the mutant resulted in disintegration of the ER-Golgi intermediate compartment (ERGIC), reduction in the level of ERGIC-53 protein and breakdown of the Golgi in many cells. Overexpression of the frameshift mutant partially inhibited the transport of wild type connexin 50 to the plasma membrane. A deletion mutant lacking the aberrant sequence showed predominant localization in the ER and inhibited anterograde protein transport suggesting, therefore, that the aberrant sequence is not responsible for improper localization of the frameshift mutant. Further deletion analysis showed that the fourth transmembrane domain and a membrane proximal region (231-294 amino acids) of the cytoplasmic domain are needed for transport from the ER and localization to the plasma membrane. Our results show that a frameshift mutant of connexin 50 mislocalizes to the ER and causes disintegration of the ERGIC and Golgi. We have also identified a sequence of connexin 50 crucial for transport from the ER and localization to the plasma membrane.

  12. ERP, Ciborgues e Memórias Protéticas

    Directory of Open Access Journals (Sweden)

    Ludmer, Gilson

    2011-11-01

    Full Text Available ERP systems have profound impacts on businesses processes and on the knowledge that employees need to carry out their activities. This essay discusses the ERP phenomenon using the metaphor of the cyborg and concepts about prosthetic memory based on the works of Haraway (2000 and Landsberg (1995. These works are used to explore aspects of ERP that seem to be otherwise obscure or camouflaged, so in need to be revealed. The cyborg can contribute to the understanding of different ways in which science and technology affect our lives, subjectivity and concepts. Issues such as complexity, changes in the workforce, changes in control strategies, identity and potential influences on knowledge and organizational actions related with ERP systems are interpreted in this essay. Finally, some questions and recommendations are presented on how to work with ERP systems.

  13. Complexity impact factors on the integration process of ERP and non ERP systems : a basis for an evaluation instrument

    NARCIS (Netherlands)

    Janssens, G.; Hoeijenbos, M.; Kusters, R.J.; Cuaresma, M.J.E.; Shishkov, B.; Cordeiro, J.

    2011-01-01

    This study shows an expert confirmed initial list of factors which influence the complexity of the integration process of ERP systems and non ERP systems. After a thorough search for complexity factors in scientific literature, a survey amongst 8 experts in a leading European long special steel

  14. ERP for Romanian Higher Education

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Also most of the big ERP providers provide solutions for higher education, including SAP AG, Oracle, JD Eduards, Peoplesoft, universities preferr other specialized applications which better fit their specific needs. This paper presents the advantages of an integrated solution for higher education and analyzes the solutions offered for this sector by the Romanian ERP market. The conlusion is more like an invitation to discussion about possible solutions to the present Romanian university situation: low budgets, changing regulations, isolated, self-developed applications.

  15. Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in ciliated tracheal epithelial cells

    Directory of Open Access Journals (Sweden)

    Olsen Colin E

    2006-08-01

    Full Text Available Abstract Background Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin α3β3γ2 (LM-332 proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC. Methods Functional coupling of RTEC was monitored by microinjection of the negatively charged fluorescent dyes, Lucifer Yellow and Alexa 350, into ciliated RTEC grown on either a LM-332/collagen or collagen matrix. Coupling of physiologically significant molecules was evaluated by the mechanism and extent of propagated intercellular Ca2+ waves. Expression of connexin (Cx mRNA and proteins were assayed by reverse transcriptase – polymerase chain reaction and immunocytochemistry, respectively. Results When compared to RTEC grown on collagen alone, RTEC grown on LM-332/collagen displayed a significant increase in dye transfer. Although mechanical stimulation of RTEC grown on either LM-332/collagen or collagen alone resulted in intercellular Ca2+ waves, the mechanism of transfer was dependent on matrix: RTEC grown on LM-332/collagen propagated Ca2+waves via extracellular purinergic signaling whereas RTEC grown on collagen used gap junctions. Comparison of RTEC grown on collagen or LM-332/collagen matrices revealed a reorganization of Cx26, Cx43 and Cx46 proteins. Conclusion Alterations in airway basement membrane proteins such as LM-332 can induce connexin reorganizations and result in altered cellular communication mechanisms that could contribute to airway tissue function.

  16. Applying Real Options for Evaluating Investments in ERP Systems

    Science.gov (United States)

    Nakagane, Jun; Sekozawa, Teruji

    This paper intends to verify effectiveness of real options approach for evaluating investments in Enterprise Resource Planning systems (ERP) and proves how important it is to disclose shadow options potentially embedded in ERP investment. The net present value (NPV) method is principally adopted to evaluate the value of ERP. However, the NPV method assumes no uncertainties exist in the object. It doesn't satisfy the current business circumstances which are filled with dynamic issues. Since the 1990s the effectiveness of option pricing models for Information System (IS) investment to solve issues in the NPV method has been discussed in the IS literature. This paper presents 3 business cases to review the practical advantages of such techniques for IS investments, especially ERP investments. The first case is EDI development. We evaluate the project by a new approach with lighting one of shadow options, EDI implementation. In the second case we reveal an ERP investment has an “expanding option” in a case of eliminating redundancy. The third case describes an option to contract which is deliberately slotted in ERP development to prepare transferring a manufacturing facility.

  17. Implantación de SAP ERP en una distribuidora

    OpenAIRE

    Martínez Costales, Guillermo

    2013-01-01

    En este trabajo se pretende reflejar en qué consistiría un proyecto de implantación de un ERP, en nuestro caso SAP ERP, en una empresa del sector de la distribución alimenticia. Para llevarlo a cabo se empleará la metodología ASAP, pretendiendo ser el resultado final del proyecto el análisis y diseño del mismo. En aquest treball es pretén reflectir en què consistiria un projecte d'implantació d'un ERP, en el nostre cas SAP ERP, en una empresa del sector de la distribució alimentària. Per f...

  18. ERP as a Support for the Knowledge Age

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available The current article presents the current situation of ERP(Enterprise Resource Planning systems and the way these systems have been changing the global economic environment. The analysis is based on a set of statistical data originating from the corporate reports and specialized literature. A special attention is paid the competitive advantages induced by using ERP at a corporate level. As a result the article identifies the main benefits of ERP systems and indicates the advantages of using such systems at a corporate level

  19. Archetypes for Managing ERP Systems

    DEFF Research Database (Denmark)

    Kræmmergaard, Pernille; Fill, Michael; Simonsen, Martin

    2007-01-01

    . In our research of 20 case-studies we found certain similarities and differences in the patterns which coalesced around three alternatives in the way organizations approach the managing of ERP in the second wave. We describe these archetypes, which we call the Calculators, the Co-players and the Drivers......, and we present illustrative cases of each of the archetypes. The archetypes are believed to play an important role in conveying the essential differences existing in alternative ways in which organizations manage their ERP system during the second wave....

  20. Archetypes for Managing ERP Systems

    DEFF Research Database (Denmark)

    Kræmmergaard, Pernille; Hansen, Michael Fiil

    2006-01-01

    . In our research of 20 case-studies we found certain similarities and differences in the patterns which coalesced around three alternatives in the way organizations approach the managing of ERP in the second wave. We describe these archetypes, which we call the Calculators, the Co-players and the Drivers......, and we present illustrative cases of each of the archetypes. The archetypes are believed to play an important role in conveying the essential differences existing in alternative ways in which organizations manage their ERP system during the second wave....

  1. Moving ERP Systems to the Cloud - Data Security Issues

    Directory of Open Access Journals (Sweden)

    Pablo Saa

    2017-08-01

    Full Text Available This paper brings to light data security issues and concerns for organizations by moving their Enterprise Resource Planning (ERP systems to the cloud. Cloud computing has become the new trend of how organizations conduct business and has enabled them to innovate and compete in a dynamic environment through new and innovative business models. The growing popularity and success of the cloud has led to the emergence of cloud-based Software-as-a-Service (SaaS ERP systems, a new alternative approach to traditional on-premise ERP systems. Cloud-based ERP has a myriad of benefits for organizations. However, infrastructure engineers need to address data security issues before moving their enterprise applications to the cloud. Cloud-based ERP raises specific concerns about the confidentiality and integrity of the data stored in the cloud. Such concerns that affect the adoption of cloud-based ERP are based on the size of the organization. Small to medium enterprises (SMEs gain the maximum benefits from cloud-based ERP as many of the concerns around data security are not relevant to them. On the contrary, larger organizations are more cautious in moving their mission critical enterprise applications to the cloud. A hybrid solution where organizations can choose to keep their sensitive applications on-premise while leveraging the benefits of the cloud is proposed in this paper as an effective solution that is gaining momentum and popularity for large organizations.

  2. ERP (enterprise resource planning) systems can streamline healthcare business functions.

    Science.gov (United States)

    Jenkins, E K; Christenson, E

    2001-05-01

    Enterprise resource planning (ERP) software applications are designed to facilitate the systemwide integration of complex processes and functions across a large enterprise consisting of many internal and external constituents. Although most currently available ERP applications generally are tailored to the needs of the manufacturing industry, many large healthcare systems are investigating these applications. Due to the significant differences between manufacturing and patient care, ERP-based systems do not easily translate to the healthcare setting. In particular, the lack of clinical standardization impedes the use of ERP systems for clinical integration. Nonetheless, an ERP-based system can help a healthcare organization integrate many functions, including patient scheduling, human resources management, workload forecasting, and management of workflow, that are not directly dependent on clinical decision making.

  3. Developmental Changes in Item and Source Memory: Evidence from an ERP Recognition Memory Study with Children, Adolescents, and Adults

    Science.gov (United States)

    Sprondel, Volker; Kipp, Kerstin H.; Mecklinger, Axel

    2011-01-01

    Event-related potential (ERP) correlates of item and source memory were assessed in 18 children (7-8 years), 20 adolescents (13-14 years), and 20 adults (20-29 years) performing a continuous recognition memory task with object and nonobject stimuli. Memory performance increased with age and was particularly low for source memory in children. The…

  4. P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of Connexin43 in Droperidol Treated Rats

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    2014-01-01

    Full Text Available Aim. This study investigated the effect of P6 EA on droperidol-induced QTc interval prolongation and Cx43 expression in ventricular muscle of rats. Methods. Twenty-four rats were randomly divided into control group (C, droperidol group (D, or EA group (E. C group rats were injected with normal saline. D group rats were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg. QTc intervals were recorded at lead II in ECG within 120 min. Cx43 expression was measured by RT-PCR and western blotting. Result. Droperidol significantly prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30 min (P0.05. Conclusion. P6 EA could improve QTc interval prolongation induced by droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120 min.

  5. Perceived Organizational ERP Benefits for SMEs: Middle Eastern Perspective

    Directory of Open Access Journals (Sweden)

    Soud Almahamid

    2015-10-01

    Full Text Available This study aims to examine the impact of organizational environment (top management support, company-wide support, business process reengineering, effective project management, and organizational culture and enterprise resource planning (ERP vendor environment (ERP vendor support on ERP perceived benefits. In order to achieve the study’s aim, a questionnaire was developed based on the extant literature to collect relevant data from the research informants. The population for this research consisted of all users of Microsoft Dynamics Great Plains (a typical type of enterprise system, which is frequently used in Jordanian companies in Amman City. A random sample of 30% of the research population was selected. The results revealed that business process reengineering, effective project management, company-wide support, and organizational culture have a positive correlation with ERP perceived benefits, whereas top management support does not. In addition, there is a significant positive correlation between vendor support and ERP perceived benefits. Academic and practical recommendations are provided.

  6. Level of Harmonization and ERP Architecture in Multinational Corporations

    DEFF Research Database (Denmark)

    Rahimi, Fatemeh; Møller, Charles

    2013-01-01

    multinational corporations. The ERP distribution decision in MNCs has been mainly associated with the corporate strategy and governance structure. As global ERP deployment benefits mainly come from business consolidation, and as there are significant costs and risks associated with centralized ERP...... to be more directly affected by the factors prohibiting further divergence, namely the corporate business process governance structure and the degree of similarity of its business models....

  7. Confronting, Confirming, and Dispelling Myths Surrounding ERP-in-the-Cloud

    DEFF Research Database (Denmark)

    Beaulieu, Tanya; C. Martin, Todd; Sarker, Saonee

    2015-01-01

    on the topic, there is substantial uncertainty surrounding the benefits and challenges of ERP cloud computing. Consequently, as often is the case with new technologies, popular myths surrounding the technology are used to make adoption and implementation decisions. As a first step toward providing an informed...... with stakeholders related to an ERP cloud-based solution. Our results dispel some of the myths, while supporting others, and highlight how ERP vendors work around the different types of challenges surrounding this technology. Our study also helps understand the benefits of ERP cloud computing, and informs about how...

  8. On the relationship between perceived importance of ERP systems selection characteristics and satisfaction with selected ERP systems in these characteristics

    DEFF Research Database (Denmark)

    Sudzina, Frantisek; Pucihar, Andreja; Lenart, Gregor

    2011-01-01

    of the relationship between the two. The paper focuses on the correlation between importance of ERP system selection criteria and the level of satisfaction with the chosen ERP systems in these characteristics. The research hypothesis is that there exists a correlation between the two. The analysis presented...

  9. Functional Role of the Disulfide Isomerase ERp57 in Axonal Regeneration.

    Directory of Open Access Journals (Sweden)

    Valentina Castillo

    Full Text Available ERp57 (also known as grp58 and PDIA3 is a protein disulfide isomerase that catalyzes disulfide bonds formation of glycoproteins as part of the calnexin and calreticulin cycle. ERp57 is markedly upregulated in most common neurodegenerative diseases downstream of the endoplasmic reticulum (ER stress response. Despite accumulating correlative evidence supporting a neuroprotective role of ERp57, the contribution of this foldase to the physiology of the nervous system remains unknown. Here we developed a transgenic mouse model that overexpresses ERp57 in the nervous system under the control of the prion promoter. We analyzed the susceptibility of ERp57 transgenic mice to undergo neurodegeneration. Unexpectedly, ERp57 overexpression did not affect dopaminergic neuron loss and striatal denervation after injection of a Parkinson's disease-inducing neurotoxin. In sharp contrast, ERp57 transgenic animals presented enhanced locomotor recovery after mechanical injury to the sciatic nerve. These protective effects were associated with enhanced myelin removal, macrophage infiltration and axonal regeneration. Our results suggest that ERp57 specifically contributes to peripheral nerve regeneration, whereas its activity is dispensable for the survival of a specific neuronal population of the central nervous system. These results demonstrate for the first time a functional role of a component of the ER proteostasis network in peripheral nerve regeneration.

  10. Produktionslogistik mit ERP-Systemen

    Science.gov (United States)

    Bauer, Jürgen

    Im Folgenden werden die Teilprozesse der Produktionslogistik bei Eigenfertigung unter Einsatz des ERP-Systems SAP R/3 beschrieben. Dabei wird die häufigste Fertigungsart, die kundenanonyme Losfertigung, zugrundegelegt.

  11. CDDIS_GNSS_products_erp

    Data.gov (United States)

    National Aeronautics and Space Administration — Earth Rotation Parameters (ERPs) derived from analysis of Global Navigation Satellite System (GNSS) data. These products are the generated by analysis centers in...

  12. ERP řešení v podnikové praxi

    OpenAIRE

    Kupka, Tomáš

    2013-01-01

    This Bachelor thesis deals with the ERP systems, which is part of the higher whole of business informatics or information system. It answers the questions about substance and inclusion of ERP solutions in the framework of information system, its classification from several aspects, historical development, market availability and product range of ERP market and management methods. Among others it deals with other extended and additional modules of ERP. All these theoretical pieces of knowledge...

  13. ERP in het grootbouwbedrijf: evaluatie van recente implementaties

    NARCIS (Netherlands)

    Leuven, A.; Voordijk, Johannes T.; Laan, Albertus

    2003-01-01

    Bijna alle grote bouwbedrijven hebben de afgelopen jaren veel geïnvesteerd in Enterprise Resource Planning (ERP) systemen als Baan, Metacom en SAP. Deze ERP-systemen hebben tot doel de verschillende bedrijfsprocessen binnen de onderneming te integreren. In grote bouwbedrijven blijkt echter de

  14. Customer requirements based ERP customization using AHP technique

    NARCIS (Netherlands)

    Parthasarathy, S.; Daneva, Maia

    2014-01-01

    Purpose– Customization is a difficult task for many organizations implementing enterprise resource planning (ERP) systems. The purpose of this paper is to develop a new framework based on customers’ requirements to examine the ERP customization choices for the enterprise. The analytical hierarchy

  15. An applicable approach for performance auditing in ERP

    Directory of Open Access Journals (Sweden)

    Wan Jian Guo

    2016-01-01

    Full Text Available This paper aims at the realistic problem of performance auditing in ERP environment. Traditional performance auditing methods and existing approaches for performance evaluation of ERP implementation could not work well, because they are either difficult to work or contains certain subjective elements. This paper proposed an applicable performance auditing approach for SAP ERP based on quantitative analysis. This approach consists of 3 parts which are system utilization, data quality and the effectiveness of system control. In each part, we provide the main process to conduct the operation, especially how to calculate the online settlement rate of SAP system. This approach has played an important role in the practical auditing work. A practical case is provided at the end of this paper to describe the effectiveness of this approach. Implementation of this approach also has some significance to the performance auditing of other ERP products.

  16. Choosing Open Source ERP Systems: What Reasons Are There For Doing So?

    Science.gov (United States)

    Johansson, Björn; Sudzina, Frantisek

    Enterprise resource planning (ERP) systems attract a high attention and open source software does it as well. The question is then if, and if so, when do open source ERP systems take off. The paper describes the status of open source ERP systems. Based on literature review of ERP system selection criteria based on Web of Science articles, it discusses reported reasons for choosing open source or proprietary ERP systems. Last but not least, the article presents some conclusions that could act as input for future research. The paper aims at building up a foundation for the basic question: What are the reasons for an organization to adopt open source ERP systems.

  17. SMEs: ERP or virtual collaboration teams

    OpenAIRE

    Ale Ebrahim, Nader; Ahmed, Shamsuddin; Taha, Zahari

    2009-01-01

    Small firms are indeed the engines of global economic growth. Small and Medium Enterprises (SMEs) play an important role to promote economic development. SMEs in the beginning of implementing new technologies always face capital shortage and need technological assistance. Available ERP systems do not fulfil the specific requirements of Small firms. SMEs has scarce resources and manpower therefore many SMEs don?t have the possessions to buy and operate an ERP System. On the other hand competit...

  18. SMEs: ERP or Virtual Collaboration Teams

    OpenAIRE

    Ebrahim, Nader Ale

    2009-01-01

    Small firms are indeed the engines of global economic growth. Small and Medium Enterprises (SMEs) play an important role to promote economic development. SMEs in the beginning of implementing new technologies always face capital shortage and need technological assistance. Available ERP systems do not fulfill the specific requirements of Small firms. SMEs has scarce resources and manpower therefore many SMEs don’t have the possessions to buy and operate an ERP System. On the other hand competi...

  19. THE MODEL FOR RISK ASSESSMENT ERP-SYSTEMS INFORMATION SECURITY

    Directory of Open Access Journals (Sweden)

    V. S. Oladko

    2016-12-01

    Full Text Available The article deals with the problem assessment of information security risks in the ERP-system. ERP-system functions and architecture are studied. The model malicious impacts on levels of ERP-system architecture are composed. Model-based risk assessment, which is the quantitative and qualitative approach to risk assessment, built on the partial unification 3 methods for studying the risks of information security - security models with full overlapping technique CRAMM and FRAP techniques developed.

  20. Usability evaluation of in-housed developed ERP system

    Science.gov (United States)

    Faisal, Chaudhry Muhammad Nadeem; Shakeel Faridi, Muhammad; Javed, Zahid

    2011-10-01

    Enterprise Resource Planning systems are the combination of different business IS (Information System) applications that are designed according to the organization requirements. Generally ERP systems are suffering from complex user interface issues. Recent research shows that there is a need for improvement concerning, the user interface from their perspectives. In order to design the software applications that are easy to use, memorize and apply to new problems, we must know the users philosophy and something about learning, reminiscence and problems solving. The Usability engineering is the only way to study the deeds of users while interacting with ERP (Enterprise Resource & Planning). This paper will focus on the users' experiences view of financial module in ERP system. The HCI research method, explicitly survey questionnaire method was adopted to gather users understanding in order to evaluate the selected modules for in-housed ERP system. The study involved group of users from two industries, the results can not be generalized as a whole. The study was first time successfully applied Usability evaluation on in-housed ERP in local industry (Masood Textile Mills, Interloop Ltd) in Pakistan. The results may hopefully opened-up an area of research and methodology that could provide considerable further benefits to Industry in developments of Industrial information systems.

  1. Critical success factors for offshoring of enterprise resource planning (ERP implementations

    Directory of Open Access Journals (Sweden)

    Rajneesh Chauhan

    2012-01-01

    Full Text Available Background: In recent years, offshoring enterprise resource planning (ERP implementation has been an emerging trend in the field of offshoring information technology (IT. However, both ERP implementations and IT offshoring are fraught with risks, and when both ERP implementation and IT offshoring happen together, the risks become even more pronounced. Therefore, it is important to understand and identify the issues of ERP implementation in an offshoring situation. Objectives: The purpose of this paper is to highlight the key factors that enable successful offshoring ERP implementation from the client and the vendor perspective. Methods/Approach: The paper uses literature as a basis for identifying a critical success factor, data collected through semi-structured interviews with ERP managers at various levels of the subject organizations, and eventually their analysis. Results: The findings of the paper reveal that various factors are critical while implementing offshoring ERP. They include: offshoring partnership, project management, project team composition, people issues, communications and compliance of the onsite team composition. It is also noticed that ten factors are grouped into three categories: the client side, the vendor side, and both. Conclusions: Organizations are currently undertaking or considering the offshoring ERP implementation particularly from India. This paper will enable them to understand the possible challenges and areas of offshoring the ERP implementation program. The value and originality of the paper comes from the fact that up to now, ERP implementation in offshoring has not been comprehensively explored. This research provides a complete understanding of the critical success factors from the client, the vendor or both the client and the vendor perspective. It also enables researchers to analyse ili rethink ili review offshoring in different service areas.

  2. Criteria for the selection of ERP software

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available The implementation of an ERP software package is an important investment for an organization, which is characterized also by a high degree of risk. Selecting the most appropriate software is a necessary condition for a successful implementation. This paper is describing the major aspects of software selection in general and the relevant criteria in the case of ERP software.

  3. Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

    Science.gov (United States)

    Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

    2018-05-08

    Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

  4. Understanding Organizational Memory from the Integrated Management Systems (ERP

    Directory of Open Access Journals (Sweden)

    Gilberto Perez

    2013-10-01

    Full Text Available With this research, in the form of a theoretical essay addressing the theme of Organizational Memory and Integrated Management Systems (ERP, we tried to present some evidence of how this type of system can contribute to the consolidation of certain features of Organizational Memory. From a theoretical review of the concepts of Human Memory, extending to the Organizational Memory and Information Systems, with emphasis on Integrated Management Systems (ERP we tried to draw a parallel between the functions and structures of Organizational Memory and features and characteristics of ERPs. The choice of the ERP system for this study was made due to the complexity and broad scope of this system. It was verified that the ERPs adequately support many functions of the Organizational Memory, highlighting the implementation of logical processes, practices and rules in business. It is hoped that the dialogue presented here can contribute to the advancement of the understanding of organizational memory, since the similarity of Human Memory is a fertile field and there is still much to be researched.

  5. What Practitioners Think of Inter-organizational ERP Requirements Engineering Practices: Focus Group Results

    NARCIS (Netherlands)

    Daneva, Maia; Ahituv, Niv

    2011-01-01

    Empirical studies on requirements engineering for inter-organizational enterprise resource planning (ERP) systems have demonstrated that the ERP vendor-provided prescriptive models for ERP roll-outs make tacit assumptions about the ERP adopter’s context. This, in turn, leads to the implementation of

  6. Cloud ERP Adoption Opportunities and Concerns: The Role of Organizational Size

    OpenAIRE

    Johansson, Björn; Alajbegovic, Amar; Alexopoulo, Vasileios; Desalermos, Achilles

    2015-01-01

    Cloud computing has become one of the fastest growing segments of the IT industry. In the wake of this, cloud based Enterprise Resource Planning (ERP) systems have emerged as an alternative to traditional ERPs. The marketing of cloud based ERPs states that adoption require low upfront investments and can rapidly be deployed, as they are provided over the cloud. In this study we seek to unravel cloud ERP adoption by identifying and classifying opportunities and concerns often associated with c...

  7. ERP SAP-osaamisen kehittäminen Pohjois-Karjalan ammattikorkeakoulussa

    OpenAIRE

    Nuutinen, Päivi

    2012-01-01

    Opinnäytetyön tavoitteena oli tutkia, millä toimin Pohjois-Karjalan ammattikorkeakoulun liiketalouden ja tekniikan keskuksen opetushenkilöstön ERP SAP-osaamista on kehitetty ja vastaako osaaminen ulkoisten asiakkaiden tarpeisiin. Tutkimustavoitteena oli selvittää myös ne menetelmät, jotka opetushenkilöstö kokee parhaimpina ERP SAP-osaamisen kehittämisen keinoina. ERP SAP-osaamisen kehittämisessä huomioitiin ulkoisten asiakkuuksien näkemykset. Tutkimustulosten osalta tuli esille, että ty...

  8. Regulation of Connexin-Based Channels by Fatty Acids

    Science.gov (United States)

    Puebla, Carlos; Retamal, Mauricio A.; Acuña, Rodrigo; Sáez, Juan C.

    2017-01-01

    In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood. PMID:28174541

  9. ENTERPRISE RESOURCE PLANNING - ERP FOR BUSINESS AND KNOWLEDGE MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Laurenţia Elena SCURTU

    2016-06-01

    Full Text Available This article presents the advantages of using the most modern information technologies to support business objectives and to provide a real support in transforming the company's internal processes through the implementation of an ERP suitable solution. ERP systems are the right IT solution for the management of company’s resources, regardless their size, they are integrated systems that optimize and simplify the internal business processes. ERP systems supports operations from important areas such as distribution, retail, manufacturing, medical, pharmaceutical, agriculture, energy or services. The main advantages on the implementation of an integrated ERP in a company are: reducing operating costs; improving sales processes; increasing the level of orders fulfillment; improving cash flow; store optimization and more important facilitating the decision making process and knowledge management processes.

  10. Sizing ERP implementation projects: an activity-based approach

    NARCIS (Netherlands)

    Janssens, G.; Kusters, R.J.; Heemstra, F.J.

    2008-01-01

    ERP implementation projects affect large parts of an implementing organization and lead to changes in the way an organization performs its tasks. The costs needed for the effort to implement these systems are hard to estimate. Research indicates that the size of an ERP project can be a useful

  11. Development of Performance and ERPs in a Flanker Task in Children and Adolescents with Tourette Syndrome—A Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Heike Eichele

    2017-06-01

    Full Text Available Background: Tourette Syndrome (TS is a neurodevelopmental disorder with childhood-onset, with a typical decline in tic severity, as well as an increasing ability to suppress tics in late childhood and adolescence. These processes develop in parallel with general improvement of self-regulatory abilities, and performance monitoring during this age-span. Hence, changes in performance monitoring over time might provide insight into the regulation of tics in children and adolescents with TS.Method: We measured reaction time, reaction time variability, accuracy, and event-related potentials (ERP in 17 children with TS, including 10 children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD, 24 children with ADHD, and 29 typically developing children, using a modified Eriksen Flanker task in two testing sessions administered on average 4.5 years apart. We then compared task performance, as well as ERP components across groups, and over time using regression models.Results: Task performance improved in all groups with age, and behavioral differences between children with TS and controls diminished at second assessment, while differences between controls and children with ADHD largely persisted. In terms of ERP, the early P3 developed earlier in children with TS compared with controls at the first assessment, but trajectories converged with maturation. ERP component amplitudes correlated with worst-ever tic scores.Conclusions: Merging trajectories between children with TS and controls are consistent with the development of compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression, in contrast to children with ADHD. Correlations between ERP amplitudes and tic scores also support this notion.

  12. Development of Performance and ERPs in a Flanker Task in Children and Adolescents with Tourette Syndrome—A Follow-Up Study

    Science.gov (United States)

    Eichele, Heike; Eichele, Tom; Marquardt, Lynn; Adolfsdottir, Steinunn; Hugdahl, Kenneth; Sørensen, Lin; Plessen, Kerstin J.

    2017-01-01

    Background: Tourette Syndrome (TS) is a neurodevelopmental disorder with childhood-onset, with a typical decline in tic severity, as well as an increasing ability to suppress tics in late childhood and adolescence. These processes develop in parallel with general improvement of self-regulatory abilities, and performance monitoring during this age-span. Hence, changes in performance monitoring over time might provide insight into the regulation of tics in children and adolescents with TS. Method: We measured reaction time, reaction time variability, accuracy, and event-related potentials (ERP) in 17 children with TS, including 10 children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), 24 children with ADHD, and 29 typically developing children, using a modified Eriksen Flanker task in two testing sessions administered on average 4.5 years apart. We then compared task performance, as well as ERP components across groups, and over time using regression models. Results: Task performance improved in all groups with age, and behavioral differences between children with TS and controls diminished at second assessment, while differences between controls and children with ADHD largely persisted. In terms of ERP, the early P3 developed earlier in children with TS compared with controls at the first assessment, but trajectories converged with maturation. ERP component amplitudes correlated with worst-ever tic scores. Conclusions: Merging trajectories between children with TS and controls are consistent with the development of compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression, in contrast to children with ADHD. Correlations between ERP amplitudes and tic scores also support this notion. PMID:28659750

  13. Development of Performance and ERPs in a Flanker Task in Children and Adolescents with Tourette Syndrome-A Follow-Up Study.

    Science.gov (United States)

    Eichele, Heike; Eichele, Tom; Marquardt, Lynn; Adolfsdottir, Steinunn; Hugdahl, Kenneth; Sørensen, Lin; Plessen, Kerstin J

    2017-01-01

    Background: Tourette Syndrome (TS) is a neurodevelopmental disorder with childhood-onset, with a typical decline in tic severity, as well as an increasing ability to suppress tics in late childhood and adolescence. These processes develop in parallel with general improvement of self-regulatory abilities, and performance monitoring during this age-span. Hence, changes in performance monitoring over time might provide insight into the regulation of tics in children and adolescents with TS. Method: We measured reaction time, reaction time variability, accuracy, and event-related potentials (ERP) in 17 children with TS, including 10 children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), 24 children with ADHD, and 29 typically developing children, using a modified Eriksen Flanker task in two testing sessions administered on average 4.5 years apart. We then compared task performance, as well as ERP components across groups, and over time using regression models. Results: Task performance improved in all groups with age, and behavioral differences between children with TS and controls diminished at second assessment, while differences between controls and children with ADHD largely persisted. In terms of ERP, the early P3 developed earlier in children with TS compared with controls at the first assessment, but trajectories converged with maturation. ERP component amplitudes correlated with worst-ever tic scores. Conclusions: Merging trajectories between children with TS and controls are consistent with the development of compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression, in contrast to children with ADHD. Correlations between ERP amplitudes and tic scores also support this notion.

  14. Re-examination of Chinese semantic processing and syntactic processing: evidence from conventional ERPs and reconstructed ERPs by residue iteration decomposition (RIDE.

    Directory of Open Access Journals (Sweden)

    Fang Wang

    Full Text Available A number of studies have explored the time course of Chinese semantic and syntactic processing. However, whether syntactic processing occurs earlier than semantics during Chinese sentence reading is still under debate. To further explore this issue, an event-related potentials (ERPs experiment was conducted on 21 native Chinese speakers who read individually-presented Chinese simple sentences (NP1+VP+NP2 word-by-word for comprehension and made semantic plausibility judgments. The transitivity of the verbs was manipulated to form three types of stimuli: congruent sentences (CON, sentences with a semantically violated NP2 following a transitive verb (semantic violation, SEM, and sentences with a semantically violated NP2 following an intransitive verb (combined semantic and syntactic violation, SEM+SYN. The ERPs evoked from the target NP2 were analyzed by using the Residue Iteration Decomposition (RIDE method to reconstruct the ERP waveform blurred by trial-to-trial variability, as well as by using the conventional ERP method based on stimulus-locked averaging. The conventional ERP analysis showed that, compared with the critical words in CON, those in SEM and SEM+SYN elicited an N400-P600 biphasic pattern. The N400 effects in both violation conditions were of similar size and distribution, but the P600 in SEM+SYN was bigger than that in SEM. Compared with the conventional ERP analysis, RIDE analysis revealed a larger N400 effect and an earlier P600 effect (in the time window of 500-800 ms instead of 570-810ms. Overall, the combination of conventional ERP analysis and the RIDE method for compensating for trial-to-trial variability confirmed the non-significant difference between SEM and SEM+SYN in the earlier N400 time window. Converging with previous findings on other Chinese structures, the current study provides further precise evidence that syntactic processing in Chinese does not occur earlier than semantic processing.

  15. The Impact of Enterprise Resource Planning System (ERP) in a South African Company

    OpenAIRE

    Mushavhanamadi K.; Mbohwa C.

    2013-01-01

    This paper presents the findings of the investigation of ERP implementation, challenges experiences by a South African Company in ERP implementation, success factors, failures, and propose recommendations to improve ERP implementation. The data collections methods used are questionnaires. The paper contributes to discussion on ERP implementation in developing economics.

  16. Clustering ERP implementation project activities: a foundation for project size definition

    NARCIS (Netherlands)

    Janssens, G.; Kusters, R.J.; Heemstra, F.J.; Sadiq, A.; Reichert, M.; Schultz, K.; Trienekens, J.J.M.; Moller, C.; Kusters, R.J.

    2007-01-01

    The size of an ERP project can be a useful measurement for predicting the effort needed to complete an ERP implementation project. Because this measurement does not exist, research is needed to find a set of variables which can define the size of an ERP implementation project. This paper shows 21

  17. Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation?

    Directory of Open Access Journals (Sweden)

    Marijke De Bock

    2015-01-01

    Full Text Available The coordination of tissue function is mediated by gap junctions (GJs that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.

  18. ERP system usage : The role of control and empowerment

    NARCIS (Netherlands)

    Maas, J.B.G.M.; van Fenema, P.C.; Soeters, J.M.M.L.

    2014-01-01

    Organisations have made significant investments in enterprise resource planning (ERP) systems with the strategic expectation that employees will utilise this technology to enhance organisational performance. However, research indicates that ERP systems are underutilised. In order to disentangle the

  19. A Comprehensive Literature Review of the ERP research field

    DEFF Research Database (Denmark)

    Kræmmergaard, Pernille; Schlichter, Bjarne Rerup

    During the past decade ERP has attracted attention from both academic and industrial communities (Shehab, Sharp et al. 2004) and we feel that now is an opportune time for the ERP field to ask how the field has evolved and what its present state is (Chen and Hirschheim 2004). The purpose...... of this paper is to address these questions, which is done by providing an overview of the Enterprise Resource Planning (ERP) research field regardless of research discipline, research topic and research traditions. Abstracts from 723 peer-reviewed journal publications from 2000 up till 2007 have been analyzed...... according to journal, authors and year of publication, and further categorized into research discipline, research topic and methods used. The paper demonstrates that the body of academic knowledge about ERP systems has reached a certain level of maturity and several different research disciplines have...

  20. ERP IMPLANTATION: KEY FACTORS OF SUCCESS AND IMPACT ON PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Dumitru Valentin

    2008-05-01

    Full Text Available The implantation of an ERP (abbreviation for "Enterprise Resource Planning" system is an enterprise project that implies the remodeling of the information system, mostly the rethinking of management procedures within the organization. The expansion and the complexity of these projects demand a theoretical framework and « optimal practices » in order to model and to evaluate the key factors of implementation success and to analyze its impact on the organization’s performance. The research problem of our communication can be divided into three research questions: - What conceptual framework for ERP implantation? - What are the key factors of success in ERP implantation? - What is the relationship between ERP implantation and enterprise performance?

  1. An Investigation on Exhaustion of SAP ERP Users: Influence of Pace of Change and Technostress

    Directory of Open Access Journals (Sweden)

    Prashanta Kumar Roy

    2017-10-01

    Full Text Available Despite recent growing research interest on ERP research, the understanding on ERP induced exhaustion is still limited. This study examines how the pace of change of ERP functionalities and interface causes exhaustion in workplace. For this purpose, we conducted an investigation on 128 ERP users from two different organizations in Bangladesh. We extended theory of technostress by integrating pace of change of ERP system. Result suggests that pace of change on ERP system significantly affect work-overload, work-life conflict and role ambiguity on ERP users. Result also shows that work-overload and role ambiguity are strong predictors for ERP induced exhaustion.

  2. Beyond Enterprise Resource Planning (ERP): The Next Generation Enterprise Resource Planning Environment

    Science.gov (United States)

    2012-02-01

    systems can provide these business functions. • ERP system: an enterprise-wide commercial off-the-shelf (COTS) software product (e.g., SAP and Oracle...are with two Tier 1 ERP software vendors: Oracle and SAP .16 Moreover, the implementation contracts for these larger ERP system investments were only...documents/FIAR_Plan_November_2011.pdf. 16 compliance was accomplished. In the current environment, DoD’s two ERP software vendors— Oracle and SAP —and the

  3. Acceptance and Success Factors for M-Learning of ERP Systems Curricula

    Science.gov (United States)

    Scholtz, Brenda; Kapeso, Mando

    2014-01-01

    The effective training of users is a key factor of the success of Enterprise Resource Planning (ERP) system projects. This need for ERP system training is exacerbated by a demand for quality ERP consultants which is evident in Europe and in African countries, particularly in South Africa where science and technology education has been identified…

  4. ERP in agriculture: Lessons learned from the Dutch horticulture

    NARCIS (Netherlands)

    Verdouw, C.N.; Robbemond, R.M.; Wolfert, J.

    2015-01-01

    Farming nowadays is a complex managerial task that imposes stringent requirements on farm management information systems. In other sectors, Enterprise Resource Planning (ERP) systems are widely implemented to meet such requirements. This paper assesses the applicability of ERP systems in the

  5. Early differential processing of material images: Evidence from ERP classification.

    Science.gov (United States)

    Wiebel, Christiane B; Valsecchi, Matteo; Gegenfurtner, Karl R

    2014-06-24

    Investigating the temporal dynamics of natural image processing using event-related potentials (ERPs) has a long tradition in object recognition research. In a classical Go-NoGo task two characteristic effects have been emphasized: an early task independent category effect and a later task-dependent target effect. Here, we set out to use this well-established Go-NoGo paradigm to study the time course of material categorization. Material perception has gained more and more interest over the years as its importance in natural viewing conditions has been ignored for a long time. In addition to analyzing standard ERPs, we conducted a single trial ERP pattern analysis. To validate this procedure, we also measured ERPs in two object categories (people and animals). Our linear classification procedure was able to largely capture the overall pattern of results from the canonical analysis of the ERPs and even extend it. We replicate the known target effect (differential Go-NoGo potential at frontal sites) for the material images. Furthermore, we observe task-independent differential activity between the two material categories as early as 140 ms after stimulus onset. Using our linear classification approach, we show that material categories can be differentiated consistently based on the ERP pattern in single trials around 100 ms after stimulus onset, independent of the target-related status. This strengthens the idea of early differential visual processing of material categories independent of the task, probably due to differences in low-level image properties and suggests pattern classification of ERP topographies as a strong instrument for investigating electrophysiological brain activity. © 2014 ARVO.

  6. ERP adoption cost factors identification and classification: a study in SMEs

    Directory of Open Access Journals (Sweden)

    Moutaz Haddara

    2013-01-01

    Full Text Available Enterprise resource planning (ERP systems adoptions require substantial resources and investments. The majority of businesses around the globe can be considered to be small and medium sized enterprises (SMEs. Thus, SMEs are seen to be typical companies that are the cornerstone of most economies. Compared with large enterprises, an SME-context contains several characteristics, and scarcity of resources is among the top of them. For SMEs, unplanned costs escalation could pose a serious threat to their stability and survival in the market. Frequently, ERP projects have crossed their estimated budgets and schedules. Researchers and practitioners state that a prevailing number of ERP adoption projects fail due to inaccurate or to too optimistic budgets/schedules. In addition, many organizations face difficulties in identifying the potential cost factors that could occur during their ERP adoption lifecycle. While focusing on the SME-context, this research attempts to identify potential costs that could occur in ERP adoptions. The research method employed in this study targeted diverse stakeholders and experts involved in ERP projects in Egypt. This research provides a list of cost factors and their classifications that could aid adopting organizations to better estimate their needed ERP project budgets. In particular, this research explores the direct and indirect cost factors that occur in ERP adoptions in Egyptian SMEs. Also, this study investigates the influence of some SME-specific contextual factors on costs. Moreover, the paper provides a ranking of cost factors according to their impact on total adoption costs.

  7. A requirements engineering framework for cross-organizational ERP systems

    NARCIS (Netherlands)

    Daneva, Maia; Wieringa, Roelf J.

    2006-01-01

    The development of cross-organizational enterprise resource planning (ERP) solutions is becoming increasingly critical to the business strategy of many networked companies. The major function of cross-organizational ERP solutions is to coordinate work in two or more organizations. However, how to

  8. Trust at first sight: evidence from ERPs

    OpenAIRE

    Marzi, Tessa; Righi, Stefania; Ottonello, Sara; Cincotta, Massimo; Viggiano, Maria Pia

    2012-01-01

    We used event-related potentials (ERPs) to tap the temporal dynamics of first impressions based on face appearance. Participants were asked to evaluate briefly presented faces for trustworthiness and political choice. Behaviorally, participants were better at discriminating faces that were pre-rated as untrustworthy. The ERP results showed that the P100 component was enhanced for untrustworthy faces, consistently with the view that signals of potential threat are given precedence in neural pr...

  9. Analysis on the integration of ERP and e-commerce

    Science.gov (United States)

    Wang, Yongqing; Shi, Yuliana

    2017-08-01

    With the continuous development of China's modern economic construction, a variety of information technology are emerging. The new economic development characterized by e-commerce has accelerated the globalization of the economy. In face of increasingly fierce market competition, for enterprises, the constructions of ERP and e-commerce are necessary ways to enhance the core competitiveness of enterprises. At present, most of the internal ERP systems and external e-commerce systems are in relatively independent state. However, with the increasing fierce market competition, a single mode of operation has been unable to meet the requirements of enterprise development. Accordingly, the effective integration of ERP and e-commerce in the new era has become one of the most important topics for enterprise development. This paper firstly analyzes the relationship between ERP and e-commerce, and then analyzes the necessity and feasibility of integration, and finally discusses the integration strategies and technologies.

  10. Applying PPM to ERP Maintenance and Continuous Improvement Initiatives

    DEFF Research Database (Denmark)

    El-Tal, Nada Maria; Fonnesbæk, Majbrit; Kræmmergaard, Pernille

    2006-01-01

    to gain business benefits from the systems. However the ERP literature on how to do this is limited. The purpose of this article is to explore how Project Portfolio Management (PPM) from the Research and Development (R&D) literature can be applied to an ERP second wave context, when companies...... are to prioritize and select maintenance and continuous improvement initiatives. This is done by reviewing the existing literature in the fields of PPM from R&D literature and then by reviewing the existing literature about maintenance and improvement initiatives in the ERP literature, after which the two...... are compared and discussed using three case-studies. The paper contributes with a discussion on how PPM from R&D can be applied to maintenance and continuous improvement initiatives in the second wave of ERP. The paper ends with arguing that emphasis needs to be given to this field, since a conscious...

  11. ERP System Implementation: An Oil and Gas Exploration Sector Perspective

    Science.gov (United States)

    Mishra, Alok; Mishra, Deepti

    Enterprise Resource Planning (ERP) systems provide integration and optimization of various business processes which leads to improved planning and decision quality, smoother coordination between business units resulting in higher efficiency, and quicker response time to customer demands and inquiries. This paper reports challenges, opportunities and outcome of ERP implementation in Oil & Gas exploration sector. This study will facilitate in understanding transition, constraints and implementation of ERP in this sector and also provide guidelines from lessons learned in this regard.

  12. An empirical analysis of ERP adoption by oil and gas firms

    Science.gov (United States)

    Romero, Jorge

    2005-07-01

    Despite the growing popularity of enterprise-resource-planning (ERP) systems for the information technology infrastructure of large and medium-sized businesses, there is limited empirical evidence on the competitive benefits of ERP implementations. Case studies of individual firms provide insights but do not provide sufficient evidence to draw reliable inferences and cross-sectional studies of firms in multiple industries provide a broad-brush perspective of the performance effects associated with ERP installations. To narrow the focus to a specific competitive arena, I analyze the impact of ERP adoption on various dimensions of performance for firms in the Oil and Gas Industry. I selected the Oil and Gas Industry because several companies installed a specific type of ERP system, SAP R/3, during the period from 1990 to 2002. In fact, SAP was the dominant provider of enterprise software to oil and gas companies during this period. I evaluate performance of firms that implemented SAP R/3 relative to firms that did not adopt ERP systems in the pre-implementation, implementation and post-implementation periods. My analysis takes two different approaches, the first from a financial perspective and the second from a strategic perspective. Using the Sloan (General Motors) model commonly applied in financial statement analysis, I examine changes in performance for ERP-adopting firms versus non-adopting firms along the dimensions of asset utilization and return on sales. Asset utilization is more closely aligned with changes in leanness of operations, and return on sales is more closely aligned with customer-value-added. I test hypotheses related to the timing and magnitude of the impact of ERP implementation with respect to leanness of operations and customer value added. I find that SAP-adopting companies performed relatively better in terms of asset turnover than non-SAP-adopting companies during both the implementation and post-implementation periods and that SAP

  13. Cost Estimation for Cross-organizational ERP Projects: Research Perspectives

    NARCIS (Netherlands)

    Daneva, Maia; Bieman, J.; Wieringa, Roelf J.

    There are many methods for estimating size, effort, schedule and other cost aspects of IS projects, but only one specifically developed for Enterprise Resource Planning (ERP) [67] and none for simultaneous, interdependent ERP projects in a cross-organizational context. The objective of this paper is

  14. Performing ERP, Performing Society

    DEFF Research Database (Denmark)

    Koch, Christian

    suites, during the third period of ERP change. Other, more basic technology developments are more important than new software applications. A biography of a community consists of technical, organizational, financial and marketing changes and occasions. Research limitations/implications: A community...

  15. Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells

    Directory of Open Access Journals (Sweden)

    Haefliger J.-A.

    2000-01-01

    Full Text Available Connexin43 (Cx43, the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension on the expression of Cx43 in aorta and heart in three different models of experimental hypertension. Rats were made hypertensive either by clipping one renal artery (two kidney, one-clip renal (2K,1C model by administration of deoxycorticosterone and salt (DOCA-salt model or by inhibiting nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME model. After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respective controls. The same 2K,1C and DOCA-salt hypertensive animals expressed twice more Cx43 in aorta, and the 2K,1C rats showed an increase in arterial distensibility. In contrast, the aortae of L-NAME hypertensive rats were characterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was more phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or control rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell communication mediated by Cx43 channels may contribute to regulating the elasticity of the vascular wall.

  16. Patterns of Technochange Management in ERP Multisite Implementations

    DEFF Research Database (Denmark)

    Carugati, Andrea; Gibson, Cyrus; Mola, Lapo

    2009-01-01

    % of the total costs of implementation, small in comparison to installation and testing (45%) and, most significantly, deployment or actually achieving effective use of technology (36%). Douplaga and Astani [7] in a survey conducted among companies of various size to discovered the major issues concerning ERP......, customizations and training. This study focus therefore on the knowledge and training issues in multisite ERP implementations and proposes a contingent approach to implementation strategies in accordance to the level of knowledge possessed by the company in the ERP technology. ...... problems in getting business results from pervasive IT-related "technochanges". Technochange [4] refers to big, technology-driven, technology-dependent change seeking significant strategic benefits and requiring significant organizational change. From the management point of view these projects differ from...

  17. A FRAMEWORK FOR CLASSIFYING MISFITS BETWEEN ENTERPRISE RESOURCE PLANNING (ERP SYSTEMS AND BUSINESS STRATEGIES

    Directory of Open Access Journals (Sweden)

    Rosnah Idrus

    2011-07-01

    Full Text Available Enterprise resource planning (ERP is a broad set of activities that is supported by multi- module application software that helps manufacturers or other businesses manage their activities. ERP is more than a software package; it includes the efforts and activities to integrate internal and external management information, business process automation and reengineering, and organisation structure streamlining. Thus, ERP eventually leads to an efficient and competitive business. Despite the prominence of ERP systems, approximately three-quarters of ERP projects are deemed as failures. Most failures are attributed to the misfit between pre-loaded business models in the ERP system and business requirements in the real world. This paper introduces a framework to classify ERP misfits into logical categories that provide insights for solution derivation. Subsequently, the classification methods are applied to a case study. Practitioners can use the misfit classification method to derive corresponding actions as solutions for ERP misfits based on their nature or specificity. In addition, the theoretical contribution of the ERP misfit problem is explored to provide information for researchers to determine appropriate theories and concepts explaining this domain.

  18. An empirical identification and categorisation of training best practices for ERP implementation projects

    Science.gov (United States)

    Esteves, Jose Manuel

    2014-11-01

    Although training is one of the most cited critical success factors in Enterprise Resource Planning (ERP) systems implementations, few empirical studies have attempted to examine the characteristics of management of the training process within ERP implementation projects. Based on the data gathered from a sample of 158 respondents across four stakeholder groups involved in ERP implementation projects, and using a mixed method design, we have assembled a derived set of training best practices. Results suggest that the categorised list of ERP training best practices can be used to better understand training activities in ERP implementation projects. Furthermore, the results reveal that the company size and location have an impact on the relevance of training best practices. This empirical study also highlights the need to investigate the role of informal workplace trainers in ERP training activities.

  19. Data of the molecular dynamics simulations of mutations in the human connexin46 docking interface

    Directory of Open Access Journals (Sweden)

    Patrik Schadzek

    2016-06-01

    The data described here are related to the research article entitled “The cataract related mutation N188T in human connexin46 (hCx46 revealed a critical role for residue N188 in the docking process of gap junction channels” (Schadzek et al., 2015 [1].

  20. The influence of enterprise resource planning (ERP) systems' performance on earnings management

    Science.gov (United States)

    Tsai, Wen-Hsien; Lee, Kuen-Chang; Liu, Jau-Yang; Lin, Sin-Jin; Chou, Yu-Wei

    2012-11-01

    We analyse whether there is a linkage between performance measures of enterprise resource planning (ERP) systems and earnings management. We find that earnings management decreases with the higher performance of ERP systems. The empirical result is as expected. We further analyse how the dimension of the DeLone and McLean model of information systems success affects earnings management. We find that the relationship between the performance of ERP systems and earnings management depends on System Quality after ERP implementation. The more System Quality improves, the more earnings management is reduced.

  1. ERP Institutionalisation- A Quantitative Data Analysis Using The Integrative Framework of IS Theories

    Directory of Open Access Journals (Sweden)

    Azadeh Pishdad

    2014-11-01

    Full Text Available There is a wide agreement that IT projects have disappointing success rates and often generate less value than originally promised. In the context of ERP systems, the same statistical reports exist which demonstrate an overwhelming number of failures in ERP implementations. A thorough review of IS literature, however, leads us to believe that organisations that broadly deploy and routinise IT (in particular, ERPs into their day-to-day work procedures realise the greatest productivity benefit and business values, and in return perceive to be more successful. The stage wherein ERP is fully assimilated, widely accepted and routinised is also referred to as institutionalised ERP in the extant IS literature of institutional theory. As a result, the authors of this paper believe that studying the influence of various social, environmental, technological and organisational factors on ERP institutionalisation has significant potential in improving the chance of successful ERP projects. In doing so, this paper introduces an integrative framework of IS theories based on an in-depth review of IS literature. The survey instrument is developed to gather data on possible impacts of factors derived from each theory on ERP institutionalisation. The gathered data is then analysed using quantitative data analysis methods to shape the final hypothetical inferences. Finally, based on the data analysis results, this paper proposed valuable suggestions to business and IT managers to improve the chance of ERP success in their organisations.

  2. INTEGRATION OF E-BUSINESS WITH ERP SYSTEMS

    OpenAIRE

    Prof. Pramod Kumar; Dr.M.P.Thapliyal

    2010-01-01

    It is very important for the businesses in our country to understand the concepts and terms of e-business and to start applying them. In the 1990's, ERP systems were introduced to fulfill some of the technological requirements across functional areas within a corporate boundary. Moreover, with the exponential growth of Internet technology and the emergence of e-business, the focus of ERP systems has changed from an integrated functional focus within an organization to one reaching outside the...

  3. Evolution of ERP Systems in the Cloud: A Study on System Updates

    Directory of Open Access Journals (Sweden)

    Elise Bjelland

    2018-06-01

    Full Text Available Cloud-based enterprise resource planning (ERP systems emerged around the new millennium, and since then there has been a lack of research regarding the evolution and update processes of these systems. From the users’ perspective, updates in a traditional on-premise ERP system are carried at their own request; while cloud-based ERPs are compulsory updated. Through an established ERP lifecycle framework, this study investigates how the process of updates is conducted in a cloud ERP context, from both the users’ and vendors’ perspectives. A multiple case study was conducted in Norway at 10 client organizations, as well as a cloud ERP vendor. Our main findings suggest that the vendor and the users view the process of updates differently. The main challenges with the process of updates from the users’ perspective are the size and date of the updates, lack of information and communication during the process, and extinction of certain functionalities. Yet, the main advantages are that all system users will always have the same version of the system, users do not need to spend time on updating the system and paying attention to the ERP market, which leads to more focus on their core competences instead.

  4. Aligning ERP systems with companies' real needs: an `Operational Model Based' method

    Science.gov (United States)

    Mamoghli, Sarra; Goepp, Virginie; Botta-Genoulaz, Valérie

    2017-02-01

    Enterprise Resource Planning (ERP) systems offer standard functionalities that have to be configured and customised by a specific company depending on its own requirements. A consistent alignment is therefore an essential success factor of ERP projects. To manage this alignment, an 'Operational Model Based' method is proposed. It is based on the design and the matching of models, and conforms to the modelling views and constructs of the ISO 19439 and 19440 enterprise-modelling standards. It is characterised by: (1) a predefined design and matching order of the models; (2) the formalisation, in terms of modelling constructs, of alignment and misalignment situations; and (3) their association with a set of decisions in order to mitigate the misalignment risk. Thus, a comprehensive understanding of the alignment management during ERP projects is given. Unlike existing methods, this one includes decisions related to the organisational changes an ERP system can induce, as well as criteria on which the best decision can be based. In this way, it provides effective support and guidance to companies implementing ERP systems, as the alignment process is detailed and structured. The method is applied on the ERP project of a Small and Medium Enterprise, showing that it can be used even in contexts where the ERP project expertise level is low.

  5. Using ERP and WfM Systems for Implementing Business Processes: An Empirical Study

    Science.gov (United States)

    Aversano, Lerina; Tortorella, Maria

    Software systems mainly considered from enterprises for dealing with a business process automation belong to the following two categories: Workflow Management Systems (WfMS) and Enterprise Resource Planning (ERP) systems. The wider diffusion of ERP systems tends to favourite this solution, but there are several limitations of most ERP systems for automating business processes. This paper reports an empirical study aiming at comparing the ability of implementing business processes of ERP systems and WfMSs. Two different case studies have been considered in the empirical study. It evaluates and analyses the correctness and completeness of the process models implemented by using ERP and WfM systems.

  6. PENGEMBANGAN SISTEM HRM TERINTEGRASI DENGAN PENDEKATAN ERP

    Directory of Open Access Journals (Sweden)

    Christine Regilia Suwu

    2016-12-01

    Full Text Available Human Resources Management merupakan salah satu instrumen yang penting bagi perusahaan dalam pencapaian tujuannya. Penggunaan sistem informasi yang terintegrasi merupakan salah satu unsur penting untuk mengelola bisnis proses dalam manajemen perusahaan. ERP merupakan sistem informasi terintegrasi yang dimaksud dalam upaya peningkatan kualitas perusahaan. Khususnya untuk perusahaan distributor, pengelolaan proses bisnis secara konvensional dapat berpengaruh pada kualitas performa dari perusahaan itu sendiri. Berfokus pada HRM perusahaan distributor, penelitian membahas mengenai implementasi bisnis proses human resource management menggunakan software ERP yaitu Odoo. Penelitian dilakukan dengan menganalisa bisnis proses yang ada kemudian merancang sistem usulan yang terintegrasi lalu diimplementasikan ke dalam Odoo. Pemodelan sistem dirancang untuk mengoptimalkan pengelolaan data yang masih diproses secara konvensional. Optimalisasi dalam setiap proses bisnis meningkatkan kualitas keamanan dengan adanya pengaturan hak akses user dan keakuratan data yang didapat dengan transaksi data yang real time, serta efisiensi waktu yaitu memperkecil durasi waktu yang diperlukan untuk pencatatan dan penyimpanan dokumen dibanding secara manual. Kata Kunci: Sistem Informasi, Human Resources Management, ERP, Bussines Process Management

  7. Implementasi Sistem ERP (Enterprise Resources Planning PT Pos Indonesia : Sebuah Inisiasi dan Strategi

    Directory of Open Access Journals (Sweden)

    Anton Susanto

    2013-12-01

    Full Text Available ABSTRAK Implementasi Enterprise Resources Planning (ERP PT Pos Indonesia merupakan bagian dari strategi penguatan internal bisnis perusahaan dan pilihan yang cukup penting dalam konteks karena tidak sedikit berbagai implementasi ERP oleh perusahaan-perusahaan di Indonesia yang mengalami kegagalan baik disebabkan oleh over budget, over time dalam pengerjaan proyek, kinerja sistem yang kurang dan keuntungan yang tidak sesuai harapan (Dantes & Hasibuan, 2011. Pilihan investasi ERP ini bukan karena sebab, berbagai pengaruh lingkungan internal maupun eksternal telah menjadi dorongan tersendiri bagi perlunya ERP pada PT Posindo. Faktor eksternal dimaksud seperti iklim kompetisi yang semakin meningkat, upaya IPO (Initial Public Offering yang membutuhkan penerapan tata kelola bisnis dengan standar yang berlaku best practice dan diterima secara internasional dan berbagai kebijakan dan regulasi terkati UU Perposan dan juga peraturan tentang BUMN. Sebagai sebuah sistem terintegrasi, ERP dalam konteks internal diharapkan dapat meningkatkan efisiensi dan kinerja aset produk agar lebih meningkatkan nilai tambah bagi perusahaan, seperti Layanan Pos dan bisnis retail yang secara financial memberikan value added negatif pada tahun 2012. Dalam tahap inisiasi, implementasi ERP dilakukan secara bertahap dimulai dengan modul SAP modul FICO (Financial Controlling dengan memperhatikan kesiapan infrastruktur dan pengembangan aplikasi-aplikasi existing (in-house development agar nantinya dapat diintegrasikan dengan basis data pada ERP. ABSTRACT The implementation of Enterprise Resource Planning (ERP at PT Pos Indonesia is a part of strengthening internal business strategy and important options because there is many implementation of ERP by various companies in Indonesia that have failed either due to over-budget, over- time in construction project , the performance of the system is lacking and  benefits that are not as expected (Dantes & Hasibuan , 2011. ERP investment

  8. Map of important transactions and master data in SAP ERP

    OpenAIRE

    Schermann, Michael

    2015-01-01

    This image represents the most important transactions and master data in SAP ERP as a tube map. As such, it covers most of the content of Magal & Word (2012) Integrated Business Processes with ERP Systems. Wiley, Hoboken, NJ, USA.

  9. ERP project implementation and risk management of nuclear power enterprise

    International Nuclear Information System (INIS)

    Wang Fei

    2008-01-01

    According to the characteristic and development trend of nuclear power enterprise informatization, combined with the general ERP implementation experience, the method is proposed to ensure the successful implementation and risk management of ERP project in nuclear power enterprise. (authors)

  10. Competitive advantage in the ERP system's value-chain and its influence on future development

    Science.gov (United States)

    Johansson, Björn; Newman, Mike

    2010-02-01

    Using the resource-based view, we present a set of propositions related to enterprise resource planning (ERP) development, reflections on competitive advantage and the different roles that stakeholders play in the value-chain. This has the goal of building a foundation for future research on ERPs and how stakeholders' desire to achieve competitive advantage influence ERP development, especially when it comes to development of a more standardised or pre-customised ERP system. The propositions also act as a foundation for increasing our knowledge concerning the difficulty in developing improved ERP systems.

  11. Managing the Challenges of Leadership in ERP Implementations: An Exploratory Study of the Leadership Challenges Encountered by Project Managers Involved in ERP Implementation Projects

    Science.gov (United States)

    Wanjagi, James K.

    2013-01-01

    Increasingly, organizations are conducting more Enterprise Resource Planning (ERP) projects in order to promote organizational efficiencies. Meanwhile, minimal research has been conducted on the leadership challenges faced by project managers during the ERP project implementations and how these challenges are managed. The existing project…

  12. The relation of Cx43 and NMDA to visceral sensitization in rats with irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Jing-yu ZHANG

    2016-01-01

    Full Text Available Objective  To study the relationship between connexin 43 (Cx43 and N-methyl-D-aspartate (NMDA receptors and visceral sensitization in the rats with irritable bowel syndrome (IBS. Methods  Thirty rats were gavaged with Triehinella spiralis to reproduce the IBS model. These rats were randomly divided into IBS group, IBS+colon distension group, and IBS+STI-571+colon distension group, and other groups of normal rats were randomized into normal group and normal+colon distension group, with 10 rats in each group. Immunofluorescent double staining were used to observe the expressions of intestine Cx43 and sacral NMDA re ceptors of rats in all the groups. Results  The Cx43 and sacral NMDA expressions in the normal group, normal+colon distension group and IBS group showed no significant changes (P>0.05, however, Cx43 and sacral NMDA expressions were significantly higher in IBS rats with colon distension as compared with those in normal group, normal+colon distension group, and IBS group (P<0.05, while they were significantly lower in the IBS+STI-571+colon distension group after STI-571 intervention (P<0.05. Conclusion  Cx43 and sacral NMDA may be the most important factor of visceral sensitization in IBS rats. DOI: 10.11855/j.issn.0577-7402.2015.12.02

  13. Factors Influencing Post-Adoptive Enterprise Resource Planning (ERP) Utilization

    Science.gov (United States)

    McGinnis, Thomas C.

    2011-01-01

    Organizations expend a great deal of time, effort and money on the implementation of enterprise resource planning (ERP) systems. They are considered the price of entry for large organizations to do business. Yet the success rate of ERP systems is poor. IS literature suggests that one possible reason for this is the underutilization of these…

  14. Critical challenges in ERP implementation: A qualitative case study in the Canadian oil and gas industry

    Science.gov (United States)

    Menon, Sreekumar A.

    This exploratory qualitative single-case study examines critical challenges encountered during ERP implementation based on individual perspectives in four project roles: senior leaders, project managers, project team members, and business users, all specifically in Canadian oil and gas industry. Data was collected by interviewing participants belonging to these categories, and by analyzing project documentation about ERP implementation. The organization for the case study was a leading multinational oil and gas company having a substantial presence in the energy sector in Canada. The study results were aligned with the six management questions regarding critical challenges in ERP: (a) circumstances to implement ERP, (b) benefits and process improvements achieved, (c) best practices implemented, (d) critical challenges encountered, (e) strategies and mitigating actions used, and (f) recommendations to improve future ERP implementations. The study results highlight six key findings. First, the study provided valid circumstances for implementing ERP systems. Second, the study underscored the importance of benefits and process improvements in ERP implementation. Third, the study highlighted that adoption of best practices is crucial for ERP Implementation. Fourth, the study found that critical challenges are encountered in ERP Implementation and are significant during ERP implementation. Fifth, the study found that strategies and mitigating actions can overcome challenges in ERP implementation. Finally, the study provided ten major recommendations on how to improve future ERP implementations.

  15. Towards a product independent ERP training model: An Insight from a literature review

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Motahar

    2018-03-01

    Full Text Available ERP can be called as one of the most significant contributions of computer science and particularly information systems for the business environment which can support all complicated business process of an organisation including sale, purchase, warehouse and manufacturing into a single database. For such complex system like ERP, implementation involves much collaboration which raises the concern of the success of the project. Among most significant success and failure factors of ERP implementation cited in the literature are training and consultation. For many years the majority of ERP vendors promote their product specific training models as long-term and expensive allowing the organisation to gain knowledge of the ERP system and the way it handles the business process. However, recent studies showed that ERP training can be conducted in the short term and with minimum investment and yet to be effective. Findings triggered a signal and opened a new door for research to investigate vendor-independent training models that require limited investment in training and consultancy. This paper aims to provide an overview of the literature; highlighting the research methods and theories used by authors towards building ERP training models and methods.

  16. Neurons and satellite glial cells in adult rat lumbar dorsal root ganglia express connexin 36.

    Science.gov (United States)

    Pérez Armendariz, E Martha; Norcini, Monica; Hernández-Tellez, Beatriz; Castell-Rodríguez, Andrés; Coronel-Cruz, Cristina; Alquicira, Raquel Guerrero; Sideris, Alexandra; Recio-Pinto, Esperanza

    2018-04-01

    Previous studies have shown that following peripheral nerve injury there was a downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord; however, it is not known whether Cx36 protein is expressed in the dorsal root ganglia (DRGs), nor if its levels are altered following peripheral nerve injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using immunohistochemistry (IHC) and immunofluorescence (IF). Double staining revealed that Cx36 co-localizes with both anti-β-III tubulin, a neuronal marker, and anti-glutamine synthetase, a satellite glial cell (SGC) marker. In neurons, Cx36 staining was mostly uniform in somata and fibers of all sizes and its intensity increased at the cell membranes. This labeling pattern was in contrast with Cx36 IF dots mainly found at junctional membranes in islet beta cells used as a control tissue. Co-staining with anti-Cx43 and anti-Cx36 showed that whereas mostly uniform staining of Cx36 was found throughout neurons and SGCs, Cx43 IF puncta were localized to SGCs. Cx36 mRNA was expressed in normal lumbar DRG, and it was significantly down-regulated in L4 DRG of rats that underwent sciatic nerve injury resulting in persistent hypersensitivity. Collectively, these findings demonstrated that neurons and SGCs express Cx36 protein in normal DRG, and suggested that perturbation of Cx36 levels may contribute to chronic neuropathic pain resulting from a peripheral nerve injury. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Deployment of ERP Systems at Automotive Industries, Security Inspection (Case Study: IRAN KHODRO Automotive Company)

    Science.gov (United States)

    Ali, Hatamirad; Hasan, Mehrjerdi

    Automotive industry and car production process is one of the most complex and large-scale production processes. Today, information technology (IT) and ERP systems incorporates a large portion of production processes. Without any integrated systems such as ERP, the production and supply chain processes will be tangled. The ERP systems, that are last generation of MRP systems, make produce and sale processes of these industries easier and this is the major factor of development of these industries anyhow. Today many of large-scale companies are developing and deploying the ERP systems. The ERP systems facilitate many of organization processes and make organization to increase efficiency. The security is a very important part of the ERP strategy at the organization, Security at the ERP systems, because of integrity and extensive, is more important of local and legacy systems. Disregarding of this point can play a giant role at success or failure of this kind of systems. The IRANKHODRO is the biggest automotive factory in the Middle East with an annual production over 600.000 cars. This paper presents ERP security deployment experience at the "IRANKHODRO Company". Recently, by launching ERP systems, it moved a big step toward more developments.

  18. Configurations and implementation of payroll system using open source erp: a case study of Koperasi PT Sri

    Science.gov (United States)

    Terminanto, A.; Swantoro, H. A.; Hidayanto, A. N.

    2017-12-01

    Enterprise Resource Planning (ERP) is an integrated information system to manage business processes of companies of various business scales. Because of the high cost of ERP investment, ERP implementation is usually done in large-scale enterprises, Due to the complexity of implementation problems, the success rate of ERP implementation is still low. Open Source System ERP becomes an alternative choice of ERP application to SME companies in terms of cost and customization. This study aims to identify characteristics and configure the implementation of OSS ERP Payroll module in KKPS (Employee Cooperative PT SRI) using OSS ERP Odoo and using ASAP method. This study is classified into case study research and action research. Implementation of OSS ERP Payroll module is done because the HR section of KKPS has not been integrated with other parts. The results of this study are the characteristics and configuration of OSS ERP payroll module in KKPS.

  19. Risk assessment for enterprise resource planning (ERP) system implementations: a fault tree analysis approach

    Science.gov (United States)

    Zeng, Yajun; Skibniewski, Miroslaw J.

    2013-08-01

    Enterprise resource planning (ERP) system implementations are often characterised with large capital outlay, long implementation duration, and high risk of failure. In order to avoid ERP implementation failure and realise the benefits of the system, sound risk management is the key. This paper proposes a probabilistic risk assessment approach for ERP system implementation projects based on fault tree analysis, which models the relationship between ERP system components and specific risk factors. Unlike traditional risk management approaches that have been mostly focused on meeting project budget and schedule objectives, the proposed approach intends to address the risks that may cause ERP system usage failure. The approach can be used to identify the root causes of ERP system implementation usage failure and quantify the impact of critical component failures or critical risk events in the implementation process.

  20. ERP e a Contabilidade

    Directory of Open Access Journals (Sweden)

    Valter Augusto Krauss

    2004-07-01

    Full Text Available A evolução da tecnologia da informação ofereceu às empresas a possibilidade de possuir sistemas totalmente integrados, proporcionando às organizações obter informações desejadas no momento oportuno, dentro de suas necessidades. Estes sistemas podem ser desenvolvidos internamente ou por terceiros que, em sua maioria, oferecem mais garantia em relação ao sucesso de implementação. O Enterprise Resource Planning - ERP é um sistema de informações que englobadiversos módulos ou subsistemas, que podem ser configuráveis e atendem todas as necessidades de informações para alcançar metas, dentro de uma entidade pública ou privada, utilizando um único banco de dados, gerando informações em tempo real. O mercado mundial de produtores deste tipo de sistemas é um tanto resumido, destacando-se: SAP com 29% do mercado mundial; seguido pela Oracle com 1 0%; JD Edwards com 7% e PeopleSoft com 6%. No mercado competitivo, esta tecnologia de informação torna-se uma ferramenta importante tanto no processo operacional quanto no processo de gestão das entidades, podendo oferecer às organizações vantagem competitiva pela qualidade das informações disponíveis, proporcionada pela rapidez, segurança e confiabilidade nos dados obtidos.

  1. The organizational memory mismatch approach in the ERP usage stage

    NARCIS (Netherlands)

    van Stijn, Eveline; Wensley, Anthony; Wijnhoven, Fons

    2005-01-01

    Enterprise Resource Planning (ERP) systems not only have a broad functional scope promising to support many different business processes. They also embed many different aspects of the company’s organizational memory. Disparities can exist between those memory contents in the ERP system and related

  2. Interfering amino terminal peptides and functional implications for heteromeric gap junction formation

    Directory of Open Access Journals (Sweden)

    Richard David Veenstra

    2013-05-01

    Full Text Available Connexin43 (Cx43 is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx, including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino terminal (NT domains of these connexins was assessed using pentameric connexin sequence-specific NT domain (iNT peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9 to 13 (Ac-KLLDK-NH2 specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional (Vj voltage-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH peptide counteracted the Vj-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system.

  3. Polymorphism of Ag29(BDT)12(TPP)43- cluster: interactions of secondary ligands and their effect on solid state luminescence.

    Science.gov (United States)

    Nag, Abhijit; Chakraborty, Papri; Bodiuzzaman, Mohammad; Ahuja, Tripti; Antharjanam, Sudhadevi; Pradeep, Thalappil

    2018-05-31

    We present the first example of polymorphism (cubic & trigonal) in single crystals of an atomically precise monolayer protected cluster, Ag29(BDT)12(TPP)43-. We demonstrate that C-Hπ interactions of the secondary ligands (TPP) are dominant in a cubic lattice compared to a trigonal lattice, resulting in a greater rigidity of the structure, which in turn, results in a higher luminescence efficiency in it.

  4. ERP II: a conceptual framework for next-generation enterprise systems?

    DEFF Research Database (Denmark)

    Møller, Charles

    2005-01-01

    proposes a conceptual framework for extended enterprise resource planning (ERP II). The aim of this model is to compile present ES concepts into a comprehensive outline of ERP II, thus composing a generic map and taxonomy for corporate-wide enterprise systems. Research limitations/implications - The paper...

  5. ERP system implementation costs and selection factors of an implementation approach

    DEFF Research Database (Denmark)

    Johansson, Björn; Sudzina, Frantisek; Newman, Mike

    2011-01-01

    , which influence the implementation approach in an ERP project, cause also an increase of the project cost in a European context? Our survey was conducted in Denmark, Slovakia and Slovenia and focused on this issue. Our main findings are that: 1) the number of implemented modules influences selection......Different approaches on implementation of enterprise resource planning (ERPs) systems exist. In this article, we investigate relationship between factors influencing selection of implementation approach and companies' ability to stay within budget when implementing ERPs. The question is: do factors...... of an implementation approach; 2) companies with information strategies are more likely to stay within budget regarding ERP systems implementation. However, we also found that: 3) implementation approach does not significantly influence ability to stay within budget; 4) a clear relationship between factors influencing...

  6. Project Parameter Estimation on the Basis of an Erp Database

    Directory of Open Access Journals (Sweden)

    Relich Marcin

    2013-12-01

    Full Text Available Nowadays, more and more enterprises are using Enterprise Resource Planning (EPR systems that can also be used to plan and control the development of new products. In order to obtain a project schedule, certain parameters (e.g. duration have to be specified in an ERP system. These parameters can be defined by the employees according to their knowledge, or can be estimated on the basis of data from previously completed projects. This paper investigates using an ERP database to identify those variables that have a significant influence on the duration of a project phase. In the paper, a model of knowledge discovery from an ERP database is proposed. The presented method contains four stages of the knowledge discovery process such as data selection, data transformation, data mining and interpretation of patterns in the context of new product development. Among data mining techniques, a fuzzy neural system is chosen to seek relationships on the basis of data from completed projects stored in an ERP system.

  7. Critical success factors in ERP implementation

    Directory of Open Access Journals (Sweden)

    Blerta Abazi Chaushi

    2016-11-01

    Full Text Available This study conducts state of the art literature review of critical success factors for enterprise resource planning systems implementation success. Since research on critical success factors for ERP implementation success is very rare and fragmented, this study provides a more comprehensive list of ten factors that companies that have adopted and struggle with the implementation, as well as companies who are in the process of considering implementation of ERP system can easily adopt and follow. The main contribution of this paper is that these ten new critical success factors are identifi ed through a thorough analysis of 22 selected research papers and is more comprehensive and straightforwardly employable for use.

  8. Measurement of ERP Utilization Level of Enterprises: The Sample of Province Aydın

    Directory of Open Access Journals (Sweden)

    Özel Sebetci

    2014-06-01

    Full Text Available The aim of this study is to measure ERP usage level of enterprises in Aydın. Data was obtained from 83 enterprises in Aydın via questionnaires. Data analysis showed that the enterprises had mostly high level of the computer integration and technologies on production. However, it was found that these enterprises did not use ERP systemsat high levels. Correlations between enterprise size by the number of employees, company revenue at 2012 and ERP usage levels were established by chi square test. Correlation analysis showed that there was a significant and positive correlation between ERP characteristics and strategic advantages about ERP.

  9. EPA Administrative Order on Consent (AOC) with ERP Compliant Coke, LLC

    Science.gov (United States)

    This Administrative Order on Consent with ERP Compliant Coke was effective August 2016. The Walter Coke facility located in North Birmingham was purchased by ERP Compliant Coke, LLC in February 2016 out of bankruptcy proceedings.

  10. ESSENTIAL CHARACTERISTICS OF AN ERP SYSTEM : CONCEPTUALIZATION AND OPERATIONALIZATION

    Directory of Open Access Journals (Sweden)

    Sylvestre Uwizeyemungu

    2012-07-01

    Full Text Available The interest of firms in ERP systems has been echoed in both the scientific andprofessional literature. It is worth noting however that while this literature has becomeincreasingly abundant, there does not yet exist an operational definition of the ERP conceptthat is, if not unanimously, at least widely accepted. This constitutes a handicap for boththe research and practice communities. The present study outlines what could beconsidered as an ERP by first determining the essentially required characteristics of such asystem: integration, flexibility and transversality. Indicators are then provided in order tooperationalise these three characteristics. The study concludes by proposing a researchframework on the impact of an ERP’s key characteristics upon the performance of thesystem in a given organisational setting.

  11. Balancing uncertainty of context in ERP project estimation: an approach and a case study

    NARCIS (Netherlands)

    Daneva, Maia

    2010-01-01

    The increasing demand for Enterprise Resource Planning (ERP) solutions as well as the high rates of troubled ERP implementations and outright cancellations calls for developing effort estimation practices to systematically deal with uncertainties in ERP projects. This paper describes an approach -

  12. ERP system implementation in SMEs: exploring the influences of the SME context

    Science.gov (United States)

    Zach, Ondrej; Munkvold, Bjørn Erik; Håkon Olsen, Dag

    2014-03-01

    Small and medium-sized enterprises (SMEs) are increasingly implementing enterprise resource planning (ERP) systems. Compared to large enterprises, SMEs differ in a number of inherent characteristics, which are likely to impact the ERP system implementations. The purpose of this study is to explore these influences of the SME context on the ERP system implementation process. SME characteristics are synthesised from relevant literature and the influences of the contextual factors on various activities across the ERP life cycle are investigated. The study presents findings from a multiple case study of four SMEs. The ownership type of the companies and limited resources were identified as the most influential contextual factors. Among the ERP life-cycle phases, the implementation phase was affected most by the SME context. The case studies also illustrate the need for a more nuanced view on what should be considered general characteristics of SMEs; for example, regarding the level of IS knowledge, business processes, and market characteristics.

  13. Assessing ERP SAP implementation in the small and medium enterprises (SMEs) in Indonesia

    Science.gov (United States)

    Yohannes; Gunawan, W.; Ikhsan, R. B.; Aries

    2018-03-01

    The consistent growth of Indonesian SMEs has received attention of global IT vendors. One of major ERP player in Indonesian market such as SAP, has introduced ERP solutions for SMEs through SAP Business One. Due to its fast growth, unfortunately, there are still very few articles can be found to understand the ERP implementation in Indonesian SMEs. The article addressed the common factors that affect the successful of the ERP implementation at SMEs. They are: identifying vendor quality, opening balance data migration, and A-SAP methodology. The article applied case study method to examine the fast growth companies owned by same owners, such as: GRK, MMM, and KM25; with the objectives to identify the practical pattern of ERP implementation in SMEs that will be useful for SAP project manager and consultants.

  14. Knowledge Management ERP Curriculum Design/Mapping (Theory and Development Tools)

    Science.gov (United States)

    Swanson, Zane; Hepner, Michelle

    2011-01-01

    This study proposes a knowledge management framework for developing and managing enterprise resource planning (ERP) curriculum within business schools. Both theory and a practical implementation are addressed. The knowledge management (KM) framework has two components which utilize ERP from a big picture curriculum overview and a ground level…

  15. Empirical study of ERP systems implementation costs in Swiss SMES

    NARCIS (Netherlands)

    Equey, C.; Kusters, R.J.; Varone, S.; Montandon, N.; Cordeiro, J.; Felipe, J.

    2008-01-01

    Based on sparse literature investigating the cost of ERP systems implementation, our research uses data from a survey of Swiss SMEs having implemented ERP in order to test cost drivers. The main innovation is the proposition of a new classification of cost drivers that depend on the enterprise

  16. TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice

    Directory of Open Access Journals (Sweden)

    Sara Crespo Yanguas

    2018-03-01

    Full Text Available Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation. The present study was set up to investigate the effects of inhibition of connexin43-based hemichannels and gap junctions on liver fibrosis in mice. Liver fibrosis was induced by administration of thioacetamide to Balb/c mice for eight weeks. Thereafter, mice were treated for two weeks with TAT-Gap19, a specific connexin43 hemichannel inhibitor, or carbenoxolone, a general hemichannel and gap junction inhibitor. Subsequently, histopathological analysis was performed and markers of hepatic damage and functionality, oxidative stress, hepatic stellate cell activation and inflammation were evaluated. Connexin43 hemichannel specificity of TAT-Gap19 was confirmed in vitro by fluorescence recovery after photobleaching analysis and the measurement of extracellular release of adenosine-5′-triphosphate. Upon administration to animals, both TAT-Gap19 and carbenoxolone lowered the degree of liver fibrosis accompanied by superoxide dismutase overactivation and reduced production of inflammatory proteins, respectively. These results support a role of connexin-based signaling in the resolution of liver fibrosis, and simultaneously demonstrate the therapeutic potential of TAT-Gap19 and carbenoxolone in the treatment of this type of chronic liver disease.

  17. Symmetry in Social Construction during ERP Implementation: A Systems Security Perspective

    Directory of Open Access Journals (Sweden)

    Kennedy Njenga

    2014-03-01

    Full Text Available The principle of symmetry in enterprise resource planning (ERP systems implementation holds that the researcher should deploy impartial explanation in cases of success as in cases of failure. This article examines the symmetry intrinsic in social construction within the various stages of the ERP development life cycle, from initiation to implementation. Discourse on symmetry focuses on whether social constructs are able to influence ERP implementation positively (success or negatively (failure and whether this exposes ERP systems to information security risk. The theoretical lens of social construction of technology (SCOT theory, a theory premised on social interaction between agents and technology artefacts, is applied for this purpose. The research was quantitative with a survey having been conducted on information technology (IT and information security (IS practitioners. Results of the study highlight the significant role social construction plays because of the direct linkage it has with the implementation of information security controls in ERP systems.  The research delineated five social constructs, namely positional influence, reward influence, coercive influence, expert influence and referent influence. For purposes of this research and on the sampling criteria applied, the construct ‘expert influence’, a typology of social construction, is shown to be more domineering than other typologies of social construction and is seen as providing symmetrical balance between governing ERP security (success and risk (failure. Implications of these results for theory and practice are discussed in the main article.

  18. Gaze-independent ERP-BCIs: augmenting performance through location-congruent bimodal stimuli

    Science.gov (United States)

    Thurlings, Marieke E.; Brouwer, Anne-Marie; Van Erp, Jan B. F.; Werkhoven, Peter

    2014-01-01

    Gaze-independent event-related potential (ERP) based brain-computer interfaces (BCIs) yield relatively low BCI performance and traditionally employ unimodal stimuli. Bimodal ERP-BCIs may increase BCI performance due to multisensory integration or summation in the brain. An additional advantage of bimodal BCIs may be that the user can choose which modality or modalities to attend to. We studied bimodal, visual-tactile, gaze-independent BCIs and investigated whether or not ERP components’ tAUCs and subsequent classification accuracies are increased for (1) bimodal vs. unimodal stimuli; (2) location-congruent vs. location-incongruent bimodal stimuli; and (3) attending to both modalities vs. to either one modality. We observed an enhanced bimodal (compared to unimodal) P300 tAUC, which appeared to be positively affected by location-congruency (p = 0.056) and resulted in higher classification accuracies. Attending either to one or to both modalities of the bimodal location-congruent stimuli resulted in differences between ERP components, but not in classification performance. We conclude that location-congruent bimodal stimuli improve ERP-BCIs, and offer the user the possibility to switch the attended modality without losing performance. PMID:25249947

  19. Implantación del sistema ERP SAP R/3

    OpenAIRE

    Muñoz Fernandez, Jorge Juan

    2012-01-01

    El objetivo del presente trabajo ha sido realizar un estudio de investigación y desarrollo sobre la implantación del sistema Enterprise Resource Planning (ERP) SAP R/3 de una empresa. L'objectiu d'aquest treball final de carrera ha estat realitzar un estudi d'investigació i desenvolupament sobre la implantació del sistema Enterprise Resource Planning (ERP) SAP R/3 d'una empresa.

  20. DEMATEL METHOD IN ERP SYSTEMS FOR TSL BRANCH

    Directory of Open Access Journals (Sweden)

    Witold TORBACKI

    2017-12-01

    Full Text Available The article introduces issues concerning the implementation of key performance indicators (KPIs dedicated to the TSL (Transport-Shipping-Logistics branch. The KPIs are used in different modules of the ERP (Enterprise resource planning information systems, which support strategic decision making. Selected indicators have been used to create four perspectives of Balanced Scorecard in accordance with Balanced Scorecard methodology. Using the multi-factor method of DEMATEL (Decision Making Trial and Evaluation Laboratory analysis, the evaluation of indicators and Balanced Scorecard’s perspectives has been performed. This article can be useful to persons interested in the implementation of modern solutions in ERP applications dedicated to the TSL branch. Presented article can be useful to persons from upper management of TSL companies who are interested in modern methods of supporting strategic management and for IT system developers who are considering expanding modules of ERP software solutions dedicated to TSL industry which support strategic management and decision making.

  1. Does ERP add company value? : A study for The Netherlands and the United Kingdom

    NARCIS (Netherlands)

    Sneller, Lineke

    2010-01-01

    This study is dedicated to one of the main IT developments in the past thirty years, namely Enterprise Resource Planning (ERP). Thousands of companies have invested billions in ERP. The empirical support for the financial value of ERP implementations, however, is scarce. This led to the central

  2. Cloud Computing for Standard ERP Systems

    DEFF Research Database (Denmark)

    Schubert, Petra; Adisa, Femi

    for the operation of ERP systems. We argue that the phenomenon of cloud computing could lead to a decisive change in the way business software is deployed in companies. Our reference framework contains three levels (IaaS, PaaS, SaaS) and clarifies the meaning of public, private and hybrid clouds. The three levels......Cloud Computing is a topic that has gained momentum in the last years. Current studies show that an increasing number of companies is evaluating the promised advantages and considering making use of cloud services. In this paper we investigate the phenomenon of cloud computing and its importance...... of cloud computing and their impact on ERP systems operation are discussed. From the literature we identify areas for future research and propose a research agenda....

  3. Peranan Sistem Erp dan Perubahan Pola Kerja sebagai Upaya Meningkatkan Kinerja Perusahaan

    Directory of Open Access Journals (Sweden)

    Hendra Alianto

    2014-06-01

    Full Text Available The ERP system is an integrated system that supports the core business activities of a company. These activities include manufacturing, logistics, finance and accounting, sales and marketing, and human resources. The ERP system will help related departments in a company to share data and information, cost reduction, and improved management of business processes, which will have an impact on work activities become more efficient and more effective. The method in this research is a case study approach, analysis, evaluation of documents and data collection. This study aims to discuss how the role of the ERP system and changes in work patterns as an effort to improve the performance of companies backed by the role of the ERP system.

  4. Benefits and challenges of cloud ERP systems – A systematic literature review

    Directory of Open Access Journals (Sweden)

    Mohamed A. Abd Elmonem

    2016-12-01

    Full Text Available Enterprise Resource Planning (ERP systems provide extensive benefits and facilities to the whole enterprise. ERP systems help the enterprise to share and transfer data and information across all functions units inside and outside the enterprise. Sharing data and information between enterprise departments helps in many aspects and aims to achieve different objectives. Cloud computing is a computing model which takes place over the internet and provides scalability, reliability, availability and low cost of computer reassures. Implementing and running ERP systems over the cloud offers great advantages and benefits, in spite of its many difficulties and challenges. In this paper, we follow the Systematic Literature Review (SLR research method to explore the benefits and challenges of implementing ERP systems over a cloud environment.

  5. Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction Function and Phosphorylation in the Mouse Heart.

    Science.gov (United States)

    Palatinus, Joseph A; Gourdie, Robert G

    2016-01-01

    Diabetic patients develop larger myocardial infarctions and have an increased risk of death following a heart attack. The poor response to myocardial injury in the diabetic heart is likely related to the many metabolic derangements from diabetes that create a poor substrate in general for wound healing, response to injury and infection. Studies in rodents have implicated a role for the gap junction protein connexin 43 (Cx43) in regulating the injury response in diabetic skin wounds. In this study, we sought to determine whether diabetes alters Cx43 molecular interactions or intracellular communication in the cryoinjured STZ type I diabetic mouse heart. We found that epicardial cryoinjury size is increased in diabetic mice and this increase is prevented by preinjury insulin administration. Consistent with these findings, we found that intercellular coupling via gap junctions is decreased after insulin administration in diabetic and nondiabetic mice. This decrease in coupling is associated with a concomitant increase in phosphorylation of Cx43 at serine 368, a residue known to decrease channel conductance. Taken together, our results suggest that insulin regulates both gap junction-mediated intercellular communication and injury propagation in the mouse heart.

  6. Changes in Expression of Connexin 32, Bile Canaliculus-Like Structures, and Localization of Alkaline Phosphatase in Primary Cultures of Fetal Rat Hepatocytes

    International Nuclear Information System (INIS)

    Fukazawa, Shoko; Chida, Kohsuke; Taguchi, Meiko; Takeuchi, Akihiro; Ikeda, Noriaki

    2013-01-01

    We devised an experimental design in primary cultures of fetal rat hepatocytes for studying hepatocyte differentiation over a short period. In the present study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented medium and then for an additional 3 days in dexamethasone- or epidermal growth factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone-supplemented medium, the expression of connexin 32 increased and bile canaliculus-like structures and localization of alkaline phosphatase in the plasma membrane around bile canaliculus-like structures were maintained. Few cells incorporated bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in epidermal growth factor-supplemented medium, the expression of connexin 32 was minimally recognized, bile canaliculus-like structures were shortened or eliminated, and alkaline phosphatase was localized as numerous fine spots throughout the cytoplasm. More than 20% of all hepatocytes incorporated bromodeoxyuridine. The present study suggests that in hepatocytes, there is a close relationship among connexin 32 expression, the maintenance of bile canaliculus-like structures, and the localization of alkaline phosphatase to the plasma membrane around the bile canaliculus-like structures, and this indicates that the present experimental model is useful for studying hepatocyte differentiation over a short period

  7. Structure-Function Correlation Analysis of Connexin50 Missense Mutations Causing Congenital Cataract: Electrostatic Potential Alteration Could Determine Intracellular Trafficking Fate of Mutants

    Directory of Open Access Journals (Sweden)

    Devroop Sarkar

    2014-01-01

    Full Text Available Connexin50 (Cx50 mutations are reported to cause congenital cataract probably through the disruption of intercellular transport in the lens. Cx50 mutants that undergo mistrafficking have generally been associated with failure to form functional gap junction channels; however, sometimes even properly trafficked mutants were found to undergo similar consequences. We hereby wanted to elucidate any structural bases of the varied functional consequences of Cx50 missense mutations through in silico approach. Computational studies have been done based on a Cx50 homology model to assess conservation, solvent accessibility, and 3-dimensional localization of mutated residues as well as mutation-induced changes in surface electrostatic potential, H-bonding, and steric clash. This was supplemented with meta-analysis of published literature on the functional properties of connexin missense mutations. Analyses revealed that the mutation-induced critical alterations of surface electrostatic potential in Cx50 mutants could determine their fate in intracellular trafficking. A similar pattern was observed in case of mutations involving corresponding conserved residues in other connexins also. Based on these results the trafficking fates of 10 uncharacterized Cx50 mutations have been predicted. Further experimental analyses are needed to validate the observed correlation.

  8. Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.

    Science.gov (United States)

    Annis, Ryan P; Swahari, Vijay; Nakamura, Ayumi; Xie, Alison X; Hammond, Scott M; Deshmukh, Mohanish

    2016-12-01

    Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of prodeath BH3-only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long-term survival. © 2016 Federation of European Biochemical Societies.

  9. ERP and the changing role of IT in engineering consultancy firms

    NARCIS (Netherlands)

    Voordijk, Johannes T.; Stegwee, R.A.; Helmus, Rogier

    2005-01-01

    Purpose – In recent years, large engineering consultancy firms in the Netherlands have implemented enterprise resource planning (ERP) systems. The purpose of this study is to shed light on the changing role of information technology (IT) in these firms after implementing ERP.

  10. Framework of ERP System Implementation for SMEs In Punjab

    OpenAIRE

    Sarvjit Singh

    2012-01-01

    Enterprise resource planning (ERP) system can effectively reduce product cost, improve customer service experience, and increase enterprise competitiveness is one of the most significant information systems for Punjab enterprises, However, the successful implementation rate of ERP system/is much lower than initially planned and many enterprises did not achieve their intended goals. There are a lot of factors (e.g., high implementation costs, technical complexity, lack of well-trained employee...

  11. Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

    Science.gov (United States)

    Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

    2015-01-01

    Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

  12. Risk Management method to ERP systems implementation based os critical sucess factors

    Directory of Open Access Journals (Sweden)

    Márcio Saez Caputo

    2004-10-01

    Full Text Available From the second half of years 90, the Enterprise Resource Planning (ERP systems implementation appears like one of the main investment focus related to the use of information technology in the companies, which aimed to acquire competitive advantages through cost reduction and differentiation of products with the use of these systems. ERP implementation showed to be much more than a technology project, involving structural and managing changes, becoming a complex and high risk process for the organizations. In the literature specialized on ERP, there are many examples of the difficulties of this type of project and about implementations that had not reached the expected objectives, frustrating the expectations of the contractors. The present work describes, first of all, the development of a risk management method to ERP systems implementation, based on critical success factors. Then, a case of application of the considered method is analyzed, detailing the steps and the results gotten until the moment. To the end, evidences regarding to how the method helps to improve risk management during ERP implementations are presented.

  13. Using Software Product Line to improve ERP Engineering: Literature Review and Analysis

    Directory of Open Access Journals (Sweden)

    Raúl Mazo

    2014-10-01

    Full Text Available On the one hand, getting advantages of Enterprise Resource Planning (ERP systems largely depends on their capacity to be configured and adapted to fit the customer and domain requirements. On the other hand, product line engineering (PLE is a promising approach for configuring and adapting products by means of configuration and derivation processes. While the literature and industrial experiences show the benefits of PLE methods, techniques and tools, there is still a lack of interest in addressing ERP engineering issues with the product line strategy. Objective: The aim of this paper is to identify and analyze the different ways presented in the literature to improve ERP engineering issues with the methods, techniques and tools provided by PLE. Method: To achieve that objective, we reviewed the literature and analyzed available publications. Results: This literature review analyzes six research papers at the intersection between ERP and PLE. It shows that the product line strategy can indeed be applied for ERP configuration and customization. It further shows the evolving interest on this topic and discusses existing contributions.

  14. ERP AND BI IMPLEMENTATION IN ROMANIAN ORGANIZATIONS AND THEIR INFLUENCE ON MANAGER'S DECISION: A CASE STUDY

    Directory of Open Access Journals (Sweden)

    EDUARD EDELHAUSER

    2011-01-01

    Full Text Available ERP systems are usually complex, expensive, powerful, proprietary systems which are used widely as integrated multi-module commercial packages suitable for tailoring and adding "add-ons" as and when required. A lot of research has been done over ERP and implementation of ERP. However, most of the research so far has been done over ERP in an effort to implement it successfully in an organization. In this paper I offer the results of a case study undertaken to see the effect of ERP implementation on a few variables of manager's decision. This study has found that the job tenure and job type of an employee influences the attitudes towards ERP system.

  15. Change Management Perspectives in an ERP Module Implementation: A Case Study in a Telecommunication Company

    Directory of Open Access Journals (Sweden)

    Tota Simatupang

    2016-06-01

    Full Text Available Successful Enterprise Resource Planning (ERP projects require change management to support the integration of the ERP systems into work environment because ERP imple¬men¬tations involve lots of changes on technical infrastructures, business processes, organization structure, rules and skills of people in the organization. This study was aimed to explain the challenges in implementing an ERP module in a Indonesian telecommunication company, focusing on the change management process involves in the project. A case study at a tele¬com¬munication company was used to collect empirical data and to analyses important aspects of project arrangements that will have an impact on the change management process accompanying the ERP implementation project. The following two aspects of changes were analyzed as the impact of ERP implementation: changes in individual behaviors and changes in the organisational practices. Based on the empirical study, two important aspects of change management effectiveness in the project and post-project stage were highlighted: alignment of the organization structure to support IT-business collaboration and alignment of employee orientation towards effective use of ERP systems. Besides, this study also highlighted that it is important to plan and execute change management process in the post-project stage to obtain benefits from ERP implementation.

  16. The impact of ISP, BPR, and customization on ERP performance in manufacturing SMEs of Korea

    Directory of Open Access Journals (Sweden)

    Jong-Weon Kim

    2017-01-01

    Full Text Available Purpose - This paper aims to assess how enterprise resource planning (ERP performance of Korean small and medium enterprises in manufacturing differs according to different levels of business process reengineering (BPR, information strategic planning (ISP and ERP customization. Design/methodology/approach - A questionnaire survey was carried out in this research. Responses from 96 small and medium manufacturing companies that have adopted ERP systems were analyzed. Findings - The results of this study suggest that ISP and BPR implementation are positively correlated to ERP performance. Originality/value - While consulting and customization costs have positive impacts on ERP performance, the level of customization does not influence performance. As one of the pioneering studies that investigate the impact of BPR, ISP and ERP customization on small and medium manufacturing companies, this research contributes to both theory and practice.

  17. Organizational memory and the completeness of process modeling in ERP systems

    NARCIS (Netherlands)

    van Stijn, E.J.; Wensley, A.K.P.

    2001-01-01

    Enterprise resource planning (ERP) systems not only have a broad functional scope promising to support many different business processes, they also embed many different aspects of the company’s organizational memory. Disparities can exist between those memory contents in the ERP system and related

  18. Architecture for Integration of Distributed ERP systems and E-commerce Systems

    DEFF Research Database (Denmark)

    Frank, Lars

    2004-01-01

    This paper will use the latest research within the extended transaction models and replication methods to illustrate how to design distributed enterprise resource planning (ERP) software with high performance and availability. In a distributed ERP system, an e‐commerce server is an ordinary sales...

  19. Analyzing the effects of information technology on supply chain integration: The role of ERP success mediator

    Directory of Open Access Journals (Sweden)

    Samaneh Alimohamadian

    2014-04-01

    Full Text Available This research analyzes the effects of Information Technology (IT on Supply Chain Integration (SCI through ERP mediator by proposing a conceptual model among these components. We also hypothesize that three constructs of IT influence on enterprise resource planning (ERP success and one construct of ERP success influences on SCI. To clarify the relationships among the constructs, structural equation model (SEM is conducted to examine the model fit and seven hypotheses. The data was collected from three Iranian firms through questionnaire with 23 questions adopted by past researches. The results confirmed that top management support of IT and employees’ general IT skills factors of IT enhance ERP success, and ERP success positively influences on Supply Chain Integration, so these two IT factors influence Supply Chain Integration through ERP success. Our data unsupported negative impact of satisfaction with legacy IT system on ERP success.

  20. Analyzing relationship between ERP utilization and lean manufacturing maturity of Turkish SMEs

    DEFF Research Database (Denmark)

    Iris, Cagatay; Cebeci, Ufuk

    2014-01-01

    with rapid development of information technology (IT) and progress in modern production management strategies have emerged. Obtained results show that Turkish SMEs have widely initiated lean production practices. However, applications are in initial level in the most cases. In respect to ERP systems...... is not adequate to make an inference about relationship between ERP and lean practices. Hence, a relational model is developed to analyze correlation between use of ERP and lean manufacturing implementation in white goods manufacturing SMEs of Istanbul, Turkey. Design/methodology/approach - The examination......Purpose - The purpose of this paper is to understand how effective Turkish small and medium size enterprises (SMEs) use enterprise resource planning (ERP) systems in module aspect and to assess the adherence to lean manufacturing requirements. Obtaining each efficiency result separately...

  1. 47 CFR 97.13 - Restrictions on station location.

    Science.gov (United States)

    2010-10-01

    ... to lowest point of antenna 500 W ERP building-mounted antennas: power >500 W ERP 1 Power = PEP input to antenna except, for repeater stations only, power exclusion is based on ERP (effective radiated...

  2. Implantació ERP SAP en empresa del sector alimentari

    OpenAIRE

    Castán Ariño, Jose Luis

    2012-01-01

    Amb aquest treball es pretén oferir d'una forma global una implantació d'un sistema ERP a una empresa fictícia basant-nos en els principis de la metodologia estàndard ASAP. Con este trabajo se pretende ofrecer de una forma global una implantación de un sistema ERP en una empresa ficticia basándonos en los principios de la metodología estándar ASAP.

  3. Lean production and ERP systems in small- and medium-sized enterprises : ERP support for pull production

    NARCIS (Netherlands)

    Powell, D.; Riezebos, J.; Strandhagen, J.O.

    2013-01-01

    It is generally accepted that lean production improves manufacturing processes through the systematic application of lean practices, and equally assumed that present day IT systems, particularly ERP systems, are essential for companies seeking efficiency through organisational integration. Though

  4. ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

    Science.gov (United States)

    Nouriziabari, Seyed Berdia

    Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

  5. Maintenance Effectiveness and Target Observation System and its ERP Interface

    International Nuclear Information System (INIS)

    Soon, Han Seong; Kim, Gi Yong; Seo, Mi Ro; Jeong, Hun Jong; Choi, Kwang Hee; Hong, Sung Yull

    2005-01-01

    Maintenance effectiveness and target observation system (MENTOS) is a maintenance rule (MR) implementation software for plant personnel to collect, edit, store, and analyze all information required for the MR implementation. Potential users and the developers of MENTOS have decided that MENTOS is implemented in the ERP system of KHNP. This article describes MENTOS briefly and introduces the ERP interface of MENTOS

  6. ERP extension - Supply Chain Management (SCM

    Directory of Open Access Journals (Sweden)

    Vasile LUPSE

    2006-01-01

    Full Text Available This article presents an extension of a ERP (Enterprise Resource Planning, more precisely the Supply Chain Management (SCM, together with some personal considerations and contributions of the authors, regarding the presented concepts.

  7. How to Disable Mortal Loops of Enterprise Resource Planning (ERP Implementation: A System Dynamics Analysis

    Directory of Open Access Journals (Sweden)

    Kaveh M. Cyrus

    2018-01-01

    Full Text Available Successful Enterprise Resource Planning (ERP implementation depends upon various factors known as critical success factors (CSFs. This study developed a system dynamics model of ERP implementation based on CSFs to discuss ERP implementation complexities, which identifies the effect of CSF interrelations on different aspects of ERP project failure. Based on the model hypothesis, CSF interrelations include many causal loop dependencies. Some of these causal loops are called mortal loops, because they may cause the failure of risk reduction efforts to a more severe failure in effect of lack of system thinking on CSFs interrelations. This study discusses how system thinking works as a leverage point for overcoming ERP implementation challenges.

  8. An experience report on ERP effort estimation driven by quality requirements

    NARCIS (Netherlands)

    Erasmus, Pierre; Daneva, Maya; Schockert, Sixten

    2015-01-01

    Producing useful and accurate project effort estimates is highly dependable on the proper definition of the project scope. In the ERP service industry, the scope of an ERP service project is determined by desired needs which are driven by certain quality attributes that the client expects to be

  9. Specifying general activity clusters for ERP projects aimed at effort prediction

    NARCIS (Netherlands)

    Janssens, G.; Kusters, R.J.; Heemstra, F.J.; Gunasekaran, A.; Shea, T.

    2010-01-01

    ERP implementation projects affect large parts of an implementing organization and lead to changes in the way an organization performs its tasks. The costs needed for the effort to implement these systems are hard to estimate. Research indicates that the size of an ERP project can be a useful

  10. Using ERP Systems to Transform Business Processes: A Case Study at a Precession Engineering Company

    Directory of Open Access Journals (Sweden)

    C.K.M.Lee

    2009-10-01

    Full Text Available Enterprises nowadays strive to keep transforming their business processes in accordance with the fastchanging customer demands so as to survive the intense global competition. In an attempt to provide practitioners with an insight into ERP implementation and the resulting business performances, this paper investigate how a successful ERP implementation can help transform enterprises processes. Case based research which is based on an in-depth observation under managerial and practitioner situation. A case study at a precession engineering company is conducted to evaluate the feasibility of the proposed strategic enterprise information model. This paper focuses on the implementation of Sales & Marketing and Warehouse modules of an ERP system. The key performance indicators are used to evaluate how the ERP implementation can improve the business processes. It is found that ERP helps to improve data visibility and improve on-time delivery but less effective on improving employee productivity. This research proposes an enterprise information model to exploit what strategy should be formulate and how ERP tactic can be implemented in company to enhance enterprise competitive advantages. The strategic enterprise information model is formulated based on our in-depth case study and ERP consultant's experience.

  11. Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.

    Science.gov (United States)

    Nualart-Marti, Anna; del Molino, Ezequiel Mas; Grandes, Xènia; Bahima, Laia; Martin-Satué, Mireia; Puchal, Rafel; Fasciani, Ilaria; González-Nieto, Daniel; Ziganshin, Bulat; Llobet, Artur; Barrio, Luis C; Solsona, Carles

    2013-12-01

    Extracellular purines elicit strong signals in the nervous system. Adenosine-5'-triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous system could be an important source of ATP in peripheral nerves. We triggered the release of ATP in vivo from mice sciatic nerves by electrical stimulation and from cultured SCs by high extracellular potassium concentration-evoked depolarization. No ATP was detected in the extracellular media after treatment of the sciatic nerve with Octanol or Carbenoxolone, and ATP release was significantly inhibited after silencing Cx32 from SCs cultures. We investigated the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis oocytes. We found that ATP release is coupled to the inward tail current generated after the activation of Cx32 hemichannels by depolarization pulses, and it is sensitive to low extracellular calcium concentrations. Moreover, we found altered ATP release in mutated Cx32 hemichannels related to the X-linked form of Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in peripheral nerves could underlie the physiopathology of this neuropathy. Copyright © 2013 Wiley Periodicals, Inc.

  12. Understanding Organizational Memory from the Integrated Management Systems (ERP)

    OpenAIRE

    Gilberto Perez; Isabel Ramos

    2013-01-01

    With this research, in the form of a theoretical essay addressing the theme of Organizational Memory and Integrated Management Systems (ERP), we tried to present some evidence of how this type of system can contribute to the consolidation of certain features of Organizational Memory. From a theoretical review of the concepts of Human Memory, extending to the Organizational Memory and Information Systems, with emphasis on Integrated Management Systems (ERP) we tried to draw a parallel between ...

  13. A THEORETICAL ANALYSIS OF KEY POINTS WHEN CHOOSING OPEN SOURCE ERP SYSTEMS

    Directory of Open Access Journals (Sweden)

    Fernando Gustavo Dos Santos Gripe

    2011-08-01

    Full Text Available The present work is aimed at presenting a theoretical analysis of the main features of Open Source ERP systems, herein identified as success technical factors, in order to contribute to the establishment of parameters to be used in decision-making processes when choosing a system which fulfills the organization´s needs. Initially, the life cycle of ERP systems is contextualized, highlighting the features of Open Source ERP systems. As a result, it was verified that, when carefully analyzed, these systems need further attention regarding issues of project continuity and maturity, structure, transparency, updating frequency, and support, all of which are inherent to the reality of this type of software. Nevertheless, advantages were observed in what concerns flexibility, costs, and non-discontinuity as benefits. The main goal is to broaden the discussion about the adoption of Open Source ERP systems.

  14. ERP implementation: an integrated process of radical change and continuous learning

    DEFF Research Database (Denmark)

    Kræmmergaard, Pernille; Møller, Charles; Boer, Harry

    2003-01-01

    This paper seeks to develop management theory that can be used to increase the likelihood of ERP implementation success. The paper argues and demonstrates that an ERP implementation can be understood as an intended radical change that can be managed to some extent. But during the use of the syste...

  15. Does ERP Hands-On Experience Help Students Learning Business Process Concepts?

    Science.gov (United States)

    Rienzo, Thomas; Han, Bernard

    2011-01-01

    Over the past decade, more and more business schools are attempting to teach business processes (BPs) by using enterprise resource planning (ERP) software in their curricula. Currently, most studies involving ERP software in the academy have concentrated on learning and teaching via self-assessment surveys or curriculum integration. This research…

  16. Evaluation of effectiveness of information systems implementation in organization (by example of ERP-systems)

    Science.gov (United States)

    Demyanova, O. V.; Andreeva, E. V.; Sibgatullina, D. R.; Kireeva-Karimova, A. M.; Gafurova, A. Y.; Zakirova, Ch S.

    2018-05-01

    ERP in a modern enterprise information system allowed optimizing internal business processes, reducing production costs and increasing the attractiveness of enterprises for investors. It is an important component of success in the competition and an important condition for attracting investments in the key sector of the state. A vivid example of these systems are enterprise information systems using the methodology of ERP (Enterprise Resource Planning - enterprise resource planning). ERP is an integrated set of methods, processes, technologies and tools. It is based on: supply chain management; advanced planning and scheduling; sales automation; tool responsible for configuring; final resource planning; intelligence business; OLAP technology; block e- Commerce; management of product data. The main purpose of ERP systems is the automation of interrelated processes of planning, accounting and management in key areas of the company. ERP systems are automated systems that effectively address complex problems, including optimal allocation of business resources, ensuring quick and efficient delivery of goods and services to the consumer. Knowledge embedded in ERP systems provided enterprise-wide automation to introduce the activities of all functional departments of the company as a single complex system. At the level of quality estimates, most managers understand that the implementations of ERP systems is a necessary and useful procedure. Assessment of the effectiveness of the information systems implementation is relevant.

  17. HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes.

    Science.gov (United States)

    Lin, Pei-Chun; Shen, Chien-Chang; Liao, Chih-Kai; Jow, Guey-Mei; Chiu, Chi-Ting; Chung, Tun-Hui; Wu, Jiahn-Chun

    2013-05-01

    HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] is a new analogue of the anti-tumor compound combretastatin A-4 containing a cis-stilbene moiety. In this study, we investigated its effects on Cx43 gap junction intercellular communication (GJIC) and the signaling pathway involved in rat primary astrocytes. Western blot analyses showed that HYS-32 dose- and time-dependently upregulated Cx43 expression. A confocal microscopic study and scrape-loading/dye transfer analyses demonstrated that HYS-32 (5μM) induced microtubule coiling, accumulation of Cx43 in gap junction plaques, and increased GJIC in astrocytes. The HYS-32-induced microtubule coiling and Cx43 accumulation in gap junction plaques was reversed when HYS-32 was removed. Treatment of astrocytes with cycloheximide resulted in time-dependent degradation of by co-treatment with HYS-32 by increasing the half-life of Cx43. Co-treatment with HYS-32 also prevented the LPS-induced downregulation of Cx43 and inhibition of GJIC in astrocytes. HYS-32 induced activation of PKC, ERK, and JNK, and co-treatment with the PKC inhibitor Go6976 or the ERK inhibitor PD98059, but not the JNK inhibitor SP600125, prevented the HYS-32-induced increase in Cx43 expression and GJIC. Go6976 suppressed the HYS-32-induced PKC phosphorylation and increase in phospho-ERK levels, while PD98059 did not prevent the HYS-32-induced increase in phospho-PKC levels, suggesting that PKC is an upstream effector of ERK. In conclusion, our results show that HYS-32 increases the half-life of Cx43 and enhances Cx43 expression and GJIC in astrocytes via a PKC-ERK signaling cascade. These novel biological effects of HYS-32 on astrocyte gap junctions support its potential for therapeutic use as a protective agent for the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The Strategic Academic Enterprise: Why ERPs Will No Longer Be Adequate

    Science.gov (United States)

    Jones, Mary

    2009-01-01

    In the 1970s and '80s, manufacturing firms began purchasing centralized administrative software--"Enterprise Resource Planning (ERP) systems"--to support their infrastructure needs. In the 1990s, higher education adopted the term ERP to define the back-office systems used by institutions to meet their most pressing business needs--typically those…

  19. Moving ERP Systems to the Cloud - Data Security Issues

    OpenAIRE

    Pablo Saa; Andrés Cueva Costales; Oswaldo Moscoso-Zea; Sergio Lujan-Mora

    2017-01-01

    This paper brings to light data security issues and concerns for organizations by moving their Enterprise Resource Planning (ERP) systems to the cloud. Cloud computing has become the new trend of how organizations conduct business and has enabled them to innovate and compete in a dynamic environment through new and innovative business models. The growing popularity and success of the cloud has led to the emergence of cloud-based Software-as-a-Service (SaaS) ERP systems, a new alternative appr...

  20. PRIMERJAVA ERP REŠITEV MICROSOFT DYNAMICS NAV IN SAP

    OpenAIRE

    Kuronja, Aleš

    2015-01-01

    Celovite informacijske rešitve (ERP) so integrirani sistemi za podporo in upravljanje poslovanja. Podpirajo različne jezike, valute in različna področja oz. panoge, v katerih poslujejo podjetja. ERP rešitve so lahko namenjene vsem velikostim podjetja, od malih do srednje velikih podjetij in vse do velikih korporacij, saj le-ti celoviti sistemi nudijo podporo večini ali vsem poslovnim procesom, ki jih izvaja vsako podjetje. V delu diplomskega projekta smo predstavili podjetji Microsoft in S...

  1. Identification of the PDI-family member ERp90 as an interaction partner of ERFAD.

    Directory of Open Access Journals (Sweden)

    Jan Riemer

    Full Text Available In the endoplasmic reticulum (ER, members of the protein disulfide isomerase (PDI family perform critical functions during protein maturation. Herein, we identify the previously uncharacterized PDI-family member ERp90. In cultured human cells, we find ERp90 to be a soluble ER-luminal glycoprotein that comprises five potential thioredoxin (Trx-like domains. Mature ERp90 contains 10 cysteine residues, of which at least some form intramolecular disulfides. While none of the Trx domains contain a canonical Cys-Xaa-Xaa-Cys active-site motif, other conserved cysteines could endow the protein with redox activity. Importantly, we show that ERp90 co-immunoprecipitates with ERFAD, a flavoprotein involved in ER-associated degradation (ERAD, through what is most likely a direct interaction. We propose that the function of ERp90 is related to substrate recruitment or delivery to the ERAD retrotranslocation machinery by ERFAD.

  2. Penerapan Enterprise Resource Planning (ERP pada Sistem Pembelian, Penjualan dan Inventory Barang di Mini Market 7 Putra

    Directory of Open Access Journals (Sweden)

    Andre Nofriandi

    2015-10-01

    Full Text Available 7 Putra is one of the mini market located on the Pasar Sungai Sariak. Purchasing, sales, and inventory of goods on this market mini is done without using a computer. It can be seen from the process of buying new goods, the receipt of goods, payment to suppliers, inventories in storage, movement of goods, sales of goods and payments from customers. ll of the above processes suffer from the financial constraints and poorly controlled. Application development Enterprise Resource Planning (ERP in a mini-market 7 Putra to assist and facilitate the process of purchase, sales and inventory items. Implementation of ERP in 7 Putra done through several stages of the business process analysis, analysis of ERP selection, ERP implementation and ERP testing. In filming the analysis of business processes, use BPMN (Business Process Modeling Notation. The module used in this research is the main module purchase, sales, as well as items and inventory. Before the implementation of ERP. ERP selection was done according to the 7th Round. The results of the election analysis showed FrontAccounting application is an application that is suitable for 7 Putra. ERP implementation is done by using the application FrontAccounting. System testing is done to check and make sure it is appropriate and ERP applications can run as expected. The test is based on existing business processes in 7 Putra. Results of testing ERP accordance with existing reporting and business processes in the 7th Round

  3. How internal audit can contribute to the success of ERP implementation projects in an Irish context.

    OpenAIRE

    Bennett, John Michael Anthony

    2014-01-01

    non-peer-reviewed The aim of this study is to explore how Internal Audit can contribute towards the successful implementation of ERP (Enterprise Resource Planning) projects in an Irish context. ERP projects are well documented for high failure rates and adverse impact on receiving businesses. Although there is limited literature available concerning the role of Internal Audit within ERP implementations, there is plenty available relating to ERP implementations which document risks, problem...

  4. Flashing characters with famous faces improves ERP-based brain-computer interface performance

    Science.gov (United States)

    Kaufmann, T.; Schulz, S. M.; Grünzinger, C.; Kübler, A.

    2011-10-01

    Currently, the event-related potential (ERP)-based spelling device, often referred to as P300-Speller, is the most commonly used brain-computer interface (BCI) for enhancing communication of patients with impaired speech or motor function. Among numerous improvements, a most central feature has received little attention, namely optimizing the stimulus used for eliciting ERPs. Therefore we compared P300-Speller performance with the standard stimulus (flashing characters) against performance with stimuli known for eliciting particularly strong ERPs due to their psychological salience, i.e. flashing familiar faces transparently superimposed on characters. Our results not only indicate remarkably increased ERPs in response to familiar faces but also improved P300-Speller performance due to a significant reduction of stimulus sequences needed for correct character classification. These findings demonstrate a promising new approach for improving the speed and thus fluency of BCI-enhanced communication with the widely used P300-Speller.

  5. An approach to identify issues affecting ERP implementation in Indian SMEs

    Directory of Open Access Journals (Sweden)

    Rana Basu

    2012-06-01

    Full Text Available Purpose: The purpose of this paper is to present the findings of a study which is based on the results of a comprehensive compilation of literature and subsequent analysis of ERP implementation success issues in context to Indian Small and Medium scale Enterprises (SME’s. This paper attempts to explore the existing literature and highlight those issues on ERP implementation and further to this the researchers applied TOPSIS (Technique for order preference by similarity to ideal solution method to prioritize issues affecting successful implementation of ERP. Design/methodology/approach: Based on the literature review certain issues leading to successful ERP implementation have been identified and to identify key issues Pareto Analysis (80-20 Rule have been applied. Further to extraction of key issues a survey based on TOPSIS was carried out in Indian small and medium scale enterprises. Findings: Based on review of literature 25 issues have been identified and further Pareto analysis has been done to extract key issues which is further prioritized by applying Topsis method. Research limitations/implications: Beside those identified issues there may be other issues that need to be explored. There is scope to enhance this study by taking into consideration different type of industries and by extending number of respondents. Practical implications: By identifying key issues for SMEs, managers can better prioritize issues to make implementation process smooth without disruption. ERP vendors can take inputs from this study to change their implementation approach while targeting small scale enterprises. Originality/value: There is no published literature available which followed a similar approach in identification of the critical issues affecting ERP in small and mid-sized companies in India or in any developing economy.

  6. An ERP Selection Framework in Constructor Companies using Fuzzy AHP Approach

    Directory of Open Access Journals (Sweden)

    mohammad ali Shahhosseini

    2013-07-01

    Full Text Available The success in ERP implementation is definitely based on selecting an appropriate system which is more aligned with enterprise culture, infrastructure and requirements, and that's why ERP selection, the process and impressive criteria have been increasingly attended in recent years. The constructor companies are strongly affected by ERP systems. A successful implementation will improve their productivity and promote their performance considerably. However, it is a challenge for decision-makers to identify the real needs, define the criteria, select the acceptable vendor and purchase the most appropriate system. This study is developed to present a Fuzzy AHP-based framework for selecting ERP systems in constructor companies. In this study, the impressive criteria have been collected by reviewing previous studies and researches, a questionnaire was used to assess and define the criteria and sub-criteria’s priority. Afterward, another questionnaire was used to compare the alternatives regarding to each criteria. Eventually, the Fuzzy Analytic Hierarchical Process was used to select a system which is more aligned with the organization’s requirements and strategies

  7. Remembering the color of objects: an ERP investigation of source memory.

    Science.gov (United States)

    Cycowicz, Y M; Friedman, D; Snodgrass, J G

    2001-04-01

    Subjects studied pictures of common objects outlined in either red or green and were asked to memorize the objects and their associated colors. Event-related potentials (ERPs) were recorded during subsequent inclusion (i.e. item) and exclusion (i.e. source) memory tasks. The main goal of the experiment was to determine if brain signatures for familiarity and recollection, two behavioral processes thought to account for episodic memory performance, would be observed in the pattern of ERP results. For correctly recognized items, early, posterior old/new effects were recorded (approximately 300--600 ms) that did not differ in magnitude or scalp distribution between item and source memory tasks. A subsequent long-duration occipitally focused negativity (approximately 800 ms peak) was evident in the source but not the item memory task. The ERPs associated with 'source errors' in the source memory task also showed robust early old/new effects. However, 'source error' ERPs lacked frontal scalp activity compared to those associated with correct source attribution. The data suggest that a recollective response may require frontal involvement whereas a decision based on familiarity may not.

  8. Combining features from ERP components in single-trial EEG for discriminating four-category visual objects

    Science.gov (United States)

    Wang, Changming; Xiong, Shi; Hu, Xiaoping; Yao, Li; Zhang, Jiacai

    2012-10-01

    Categorization of images containing visual objects can be successfully recognized using single-trial electroencephalograph (EEG) measured when subjects view images. Previous studies have shown that task-related information contained in event-related potential (ERP) components could discriminate two or three categories of object images. In this study, we investigated whether four categories of objects (human faces, buildings, cats and cars) could be mutually discriminated using single-trial EEG data. Here, the EEG waveforms acquired while subjects were viewing four categories of object images were segmented into several ERP components (P1, N1, P2a and P2b), and then Fisher linear discriminant analysis (Fisher-LDA) was used to classify EEG features extracted from ERP components. Firstly, we compared the classification results using features from single ERP components, and identified that the N1 component achieved the highest classification accuracies. Secondly, we discriminated four categories of objects using combining features from multiple ERP components, and showed that combination of ERP components improved four-category classification accuracies by utilizing the complementarity of discriminative information in ERP components. These findings confirmed that four categories of object images could be discriminated with single-trial EEG and could direct us to select effective EEG features for classifying visual objects.

  9. Study of Cloud Based ERP Services for Small and Medium Enterprises (Data is Processed by Text Mining Technique

    Directory of Open Access Journals (Sweden)

    SHARMA, R.

    2014-06-01

    Full Text Available The purpose of this research paper is to explore the knowledge of the existing studies related to cloud computing current trend. The outcome of research is demonstrated in the form of diagram which simplifies the ERP integration process for in-house and cloud eco-system. It will provide a conceptual view to the new client or entrepreneurs using ERP services and explain them how to deal with two stages of ERP systems (cloud and in-house. Also suggest how to improve knowledge about ERP services and implementation process for both stages. The work recommends which ERP services can be outsourced over the cloud. Cloud ERP is a mix of standard ERP services along with cloud flexibility and low cost to afford these services. This is a recent phenomenon in enterprise service offering. For most of non IT background entrepreneurs it is unclear and broad concept, since all the research work related to it are done in couple of years. Most of cloud ERP vendors describe their products as straight forward tasks. The process and selection of Cloud ERP Services and vendors is not clear. This research work draws a framework for selecting non-core business process from preferred ERP service partners. It also recommends which ERP services outsourced first over the cloud, and the security issues related to data or information moved out from company premises to the cloud eco-system.

  10. Antecedents for the Success of the Adoption of Organizational ERP Among Higher Education Institutions and Competitive Advantage in Egypt

    Directory of Open Access Journals (Sweden)

    M. Soliman

    2017-06-01

    Full Text Available Although the Enterprise Resource Planning (ERP system has long been acknowledged in higher education institutions (HEIs to improve their performance and efficiency, there are not many HEIs in Egypt that adopt ERP system and those that do are in an early stage. The research on ERP system in HEI is still limited and in the immature stage, hence little is known about the success factors for the adoption stage of ERP systems. Consequently, this article aims to understand what are the success factors for ERP adoption and further develop a conceptual model that explains the successful implementation of ERP in HEIs and its impact on competitive advantage. Based on previous studies, this paper identifies and conceptualizes success factors for ERP and further develops the proposed model for the adoption of ERP system in HEIs. This article contributes to the development of the theoretical framework of the successful implementation of the ERP system to explain the competitive advantage of HEI by merging information system (IS success and diffusion of innovation (DOI theories with the success factors for the adoption stage of ERP systems. The current study will provide recommendations and guidelines for both the potential adopters and the vendors on the successful ERP system adoption.

  11. 29 CFR 15.23 - Restrictions on certain claims.

    Science.gov (United States)

    2010-07-01

    ... restrictions noted: (a) Money or currency. Claims may be allowed for loss of money or currency (which includes... currency is limited to an amount which is determined to have been reasonable for the claimant to have had... motor vehicles were required to be used for official Government business (official Government business...

  12. Risk Factors in ERP Implementation Projects for Process Oriented

    Directory of Open Access Journals (Sweden)

    Andrzej Partyka

    2009-09-01

    Full Text Available This paper present review and analysis of risk factors, which could affect successful implementation of ERP system, for project performed in project oriented organizations. Presented risk breakdown structure and the list of common risk factors, are well-suited for ERP implementation projects. Considered risk categories allow for complex risk analysis. Additionally, mapping of risk importance for particular implementation phases is presented. Making presented model an important input for project risk management process, especially for the beginning phases which require identification of risk factors.

  13. Function of Management Consultation in Implementation of ERP Project

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    ERP(enterprise resource planning) is a huge and com pl ex system engineering which costs a great lot of fund and manpower. It is a refo rm in the enterprise management mode, management idea and management method whi ch needs mass fund import, with long period, full of risk, hard to perform and can't show its effects at once. The essence of the enterprise performing in ERP system is to run a "management engineering", which involves integration of opera tion process. The integration will touch business ...

  14. Spatial and Time Domain Feature of ERP Speller System Extracted via Convolutional Neural Network.

    Science.gov (United States)

    Yoon, Jaehong; Lee, Jungnyun; Whang, Mincheol

    2018-01-01

    Feature of event-related potential (ERP) has not been completely understood and illiteracy problem remains unsolved. To this end, P300 peak has been used as the feature of ERP in most brain-computer interface applications, but subjects who do not show such peak are common. Recent development of convolutional neural network provides a way to analyze spatial and temporal features of ERP. Here, we train the convolutional neural network with 2 convolutional layers whose feature maps represented spatial and temporal features of event-related potential. We have found that nonilliterate subjects' ERP show high correlation between occipital lobe and parietal lobe, whereas illiterate subjects only show correlation between neural activities from frontal lobe and central lobe. The nonilliterates showed peaks in P300, P500, and P700, whereas illiterates mostly showed peaks in around P700. P700 was strong in both subjects. We found that P700 peak may be the key feature of ERP as it appears in both illiterate and nonilliterate subjects.

  15. ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching

    Science.gov (United States)

    Yeung, Nick

    2016-01-01

    Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures—memory selectivity and global memory—to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm—in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials—with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable. PMID:27907075

  16. Does bimodal stimulus presentation increase ERP components usable in BCIs?

    Science.gov (United States)

    Thurlings, Marieke E.; Brouwer, Anne-Marie; Van Erp, Jan B. F.; Blankertz, Benjamin; Werkhoven, Peter J.

    2012-08-01

    Event-related potential (ERP)-based brain-computer interfaces (BCIs) employ differences in brain responses to attended and ignored stimuli. Typically, visual stimuli are used. Tactile stimuli have recently been suggested as a gaze-independent alternative. Bimodal stimuli could evoke additional brain activity due to multisensory integration which may be of use in BCIs. We investigated the effect of visual-tactile stimulus presentation on the chain of ERP components, BCI performance (classification accuracies and bitrates) and participants’ task performance (counting of targets). Ten participants were instructed to navigate a visual display by attending (spatially) to targets in sequences of either visual, tactile or visual-tactile stimuli. We observe that attending to visual-tactile (compared to either visual or tactile) stimuli results in an enhanced early ERP component (N1). This bimodal N1 may enhance BCI performance, as suggested by a nonsignificant positive trend in offline classification accuracies. A late ERP component (P300) is reduced when attending to visual-tactile compared to visual stimuli, which is consistent with the nonsignificant negative trend of participants’ task performance. We discuss these findings in the light of affected spatial attention at high-level compared to low-level stimulus processing. Furthermore, we evaluate bimodal BCIs from a practical perspective and for future applications.

  17. Online processing of moral transgressions: ERP evidence for spontaneous evaluation.

    Science.gov (United States)

    Leuthold, Hartmut; Kunkel, Angelika; Mackenzie, Ian G; Filik, Ruth

    2015-08-01

    Experimental studies using fictional moral dilemmas indicate that both automatic emotional processes and controlled cognitive processes contribute to moral judgments. However, not much is known about how people process socio-normative violations that are more common to their everyday life nor the time-course of these processes. Thus, we recorded participants' electrical brain activity while they were reading vignettes that either contained morally acceptable vs unacceptable information or text materials that contained information which was either consistent or inconsistent with their general world knowledge. A first event-related brain potential (ERP) positivity peaking at ∼200 ms after critical word onset (P200) was larger when this word involved a socio-normative or knowledge-based violation. Subsequently, knowledge-inconsistent words triggered a larger centroparietal ERP negativity at ∼320 ms (N400), indicating an influence on meaning construction. In contrast, a larger ERP positivity (larger late positivity), which also started at ∼320 ms after critical word onset, was elicited by morally unacceptable compared with acceptable words. We take this ERP positivity to reflect an implicit evaluative (good-bad) categorization process that is engaged during the online processing of moral transgressions. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Assessing Leading ERP-SAP Implementation in Leading Firms in Indonesia

    Science.gov (United States)

    Syaiful, B.; Gunawan, W.

    2017-01-01

    Enterprise resource planning (ERP) enables to bring critical capabilities to an organisation, however, the implementation of such capabilities is often surrounded with problems. The implementing ERP-SAP in Indonesian enterprises are still facing tremendous challenges with the failure rate can reach more than 80% of the cases. The article examines the common problems faced by the consultants whenever they deal with their clients, from the practical perspectives. The article takes the multiple case studies of the leading enterprises in Indonesia, such as: KS (largest steel producer), GEM (large mining producer), and HS (large retailer), with the aim to identify the root of problems of SAP implementation. The outcome of the study is expected to provide the consultants with the guideline to understand the ERP implementation process in their clients and effective solutions to cope with it.

  19. Performance improvement of ERP-based brain-computer interface via varied geometric patterns.

    Science.gov (United States)

    Ma, Zheng; Qiu, Tianshuang

    2017-12-01

    Recently, many studies have been focusing on optimizing the stimulus of an event-related potential (ERP)-based brain-computer interface (BCI). However, little is known about the effectiveness when increasing the stimulus unpredictability. We investigated a new stimulus type of varied geometric pattern where both complexity and unpredictability of the stimulus are increased. The proposed and classical paradigms were compared in within-subject experiments with 16 healthy participants. Results showed that the BCI performance was significantly improved for the proposed paradigm, with an average online written symbol rate increasing by 138% comparing with that of the classical paradigm. Amplitudes of primary ERP components, such as N1, P2a, P2b, N2, were also found to be significantly enhanced with the proposed paradigm. In this paper, a novel ERP BCI paradigm with a new stimulus type of varied geometric pattern is proposed. By jointly increasing the complexity and unpredictability of the stimulus, the performance of an ERP BCI could be considerably improved.

  20. Investigation of the mediating effects of IT governance-value delivery on service quality and ERP performance

    Science.gov (United States)

    Tsai, Wen-Hsien; Chou, Yu-Wei; Leu, Jun-Der; Chao Chen, Der; Tsaur, Tsen-Shu

    2015-02-01

    This study aimed to explore the mediating effects of IT governance (ITG)-value delivery in the relationships among the quality of vendor service, the quality of consultant services, ITG-value delivery and enterprise resource planning (ERP) performance. The sampling of this research was acquired from a questionnaire survey concerning ERP implementations in Taiwan. In this survey, 4366 questionnaires were sent to manufacturing and service companies listed in the TOP 5000: The Largest Corporations in Taiwan 2009. The results showed that an ERP system will exhibit a decreased error rate and improved performance if ERP system vendors and consultants provide good service quality. The results also demonstrated that significant relationships exist among the quality of vendor service, the quality of consultant services and value delivery. The contribution of this article is twofold. First, it found that value delivery provides an effective measure of ERP performance under an ITG framework. Second, it provides evidence of the partial mediating effects of value delivery between service quality and ERP performance. In other words, if enterprises want to improve ERP performance, they need to consider factors such as value delivery and the quality of a vendor/consultant's service.

  1. Music training and working memory: an ERP study.

    Science.gov (United States)

    George, Elyse M; Coch, Donna

    2011-04-01

    While previous research has suggested that music training is associated with improvements in various cognitive and linguistic skills, the mechanisms mediating or underlying these associations are mostly unknown. Here, we addressed the hypothesis that previous music training is related to improved working memory. Using event-related potentials (ERPs) and a standardized test of working memory, we investigated both neural and behavioral aspects of working memory in college-aged, non-professional musicians and non-musicians. Behaviorally, musicians outperformed non-musicians on standardized subtests of visual, phonological, and executive memory. ERPs were recorded in standard auditory and visual oddball paradigms (participants responded to infrequent deviant stimuli embedded in lists of standard stimuli). Electrophysiologically, musicians demonstrated faster updating of working memory (shorter latency P300s) in both the auditory and visual domains and musicians allocated more neural resources to auditory stimuli (larger amplitude P300), showing increased sensitivity to the auditory standard/deviant difference and less effortful updating of auditory working memory. These findings demonstrate that long-term music training is related to improvements in working memory, in both the auditory and visual domains and in terms of both behavioral and ERP measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Building the hybrid organisation through ERP and enterprise social software

    OpenAIRE

    Greasley, Andrew; Wang, Yucan

    2016-01-01

    This research traces the implementation of an information system in the form of ERP modules covering tenant and contract management in a Chinese service company. Misalignments between the ERP system specification and user needs led to the adoption of informal processes within the organisation. These processes are facilitated within an informal organisational structure and are based on human interactions undertaken within the formal organisation. Rather than to attempt to suppress the emergenc...

  3. The first de novo mutation of the connexin 32 gene associated with X linked Charcot-Marie-Tooth disease

    NARCIS (Netherlands)

    Meggouh, F.; Benomar, A.; Rouger, H.; Tardieu, S.; Birouk, N.; Tassin, J.; Barhoumi, C.; Yahyaoui, M.; Chkili, T.; Brice, A.; LeGuern, E.

    1998-01-01

    X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP technique and direct sequencing of PCR amplified genomic DNA fragments of the Cx32 gene from a Moroccan patient and her relatives, we identified

  4. Sticking to standards : Technical and other isomorphic pressures in deploying ERP-systerns

    NARCIS (Netherlands)

    Benders, J.; Batenburg, R.; van der Blonk, H.C.

    This paper focuses on how and to what extent homogenization coincides with the deployment of ERP-systems. Using the work of DiMaggio and Powell on isomorphic pressures, we argue that the use of ERP-systems may in several ways lead to standardization within and between organizations. Competitive and

  5. ERP as an organization innovation : Key users and cross-boundary knowledge management

    NARCIS (Netherlands)

    Maas, J.-B.; van Fenema, P.C.; Soeters, J.M.M.L.

    2016-01-01

    Purpose The purpose of this study is to provide more insight in the ways key users act as knowledge managers and boundary spanners during the enterprise resource planning (ERP) system usage phase. Despite the recognized importance of key users during the implementation phase of an ERP system, little

  6. Evaluating the impact of ERP systems on SC performance with ISM

    Directory of Open Access Journals (Sweden)

    Cristina López Vargas

    2017-06-01

    Full Text Available Most companies nowadays have already implemented on-premise or cloud -based ERP systems into their IT infraestrutures. These packages allow firms to integrate, standardize and execute the whole business processes in real time, improving their productivity and operational efficiency. Previous studies highlight their beneficial effects go beyond the single firm. Indeed, ERP system can assist supply‐chain partners to work in close coordination. In order to reach a better understanding in this matter, the present study aims to develop a comprehensive framework. This will represent the benefits derived from ERP adoption in Supply Chain performance. In doing so, we applied an interpretive structural modelling (ISM. Finally, we provide a case study that explores the viability of this framework.

  7. Guía de selección de ERP en las pequeñas y medianas empresas mexicanas

    Directory of Open Access Journals (Sweden)

    Rivera, Igor

    2013-04-01

    Full Text Available Enterprise Resource Planning (ERP systems are information system characterised by having a shared database for all the company’s departments. Organisations use ERP sys- tems to manage their data and help improve decision-making. However, recent studies show that 92% of ERP projects do not end in success (De Pablos Heredero and De Pablos Heredero, 2009. This paper aims to design a guide to ERP selection for Mexican SMEs. It starts with a review of the scientific literature, which is divided into methodological proposals, case studies, micro-sociological studies, and critical success factors for ERP projects. To complement our theoretical study we interviewed consultants, users and ERP project experts, who supported our conception of this issue at local level. Finally, we designed an ERP selection guide.Los Enterprise Resource Planning (ERP son Sistemas de Información caracterizados por tener una base de datos común para todos los departamentos de la empresa y son utilizados por las organizaciones para administrar sus datos con el fin de tomar mejores decisiones. Sin embargo, estudios recientes demuestran que el 92% de los proyectos ERP no terminan con éxito (De Pablos Heredero y De Pablos Heredero, 2009. El objetivo de este artículo es diseñar una guía de selección de ERP en las Pymes mexicanas. En primera instancia se realizó un examen de la literatura científica, el cual se dividió en: propuestas metodológicas, casos de estudio, estudios microsociológicos y factores críticos de éxito para proyectos ERP. Para complementar nuestro estudio teórico se entrevistaron consultores, utilizadores y expertos en proyectos ERP, los cuales apoyaron nuestra concepción de esta problemática en el ámbito local. Finalmente se diseñó la guía de selección de ERP.

  8. An examination of the association between chronic sleep restriction and electrocortical arousal in college students.

    Science.gov (United States)

    Witkowski, Sarah; Trujillo, Logan T; Sherman, Stephanie M; Carter, Patricia; Matthews, Michael D; Schnyer, David M

    2015-03-01

    The deleterious neurocognitive effects of laboratory-controlled short-term sleep deprivation are well-known. The present study investigated neurocognitive changes arising from chronic sleep restriction outside the laboratory. Sleep patterns of 24 undergraduates were tracked via actigraphy across a 15-week semester. At the semester beginning, at a midpoint, and a week before finals, students performed the Psychomotor Vigilance Test (PVT) and cortical arousal was measured via event-related potentials (ERP) and resting state electroencephalography (EEG). Average daily sleep decreased between Session 1 and Sessions 2 and 3. Calculated circadian rhythm measures indicated nighttime movement increased and sleep quality decreased from Sessions 1 and 2 to Session 3. Parallel to the sleep/activity measures, PVT reaction time increased between Session 1 and Sessions 2 and 3 and resting state alpha EEG reactivity magnitude and PVT-evoked P3 ERP amplitude decreased between Session 1 and Sessions 2 and 3. Cross-sectional regressions showed PVT reaction time was negatively associated with average daily sleep, alpha reactivity, and P3 changes; sleep/circadian measures were associated with alpha reactivity and/or P3 changes. Small, but persistent sleep deficits reduced cortical arousal and impaired vigilant attention. Chronic sleep restriction impacts neurocognition in a manner similar to laboratory controlled sleep deprivation. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

  9. Exploring the Effects of Technology Overload on the Outcomes of Enterprise Resource Planning (ERP) Implementation Projects

    Science.gov (United States)

    Kates, Earl B.

    2016-01-01

    Despite significant investments made by organizations to implement ERP systems and prior research that explored contributing factors of ERP failure, the ERP implementation success rate continues to remain low in practice. Increased technology usage in the workplace coupled with higher dependency on technology to complete project tasks often leads…

  10. Application of ERPs neuromarkers for assessment and treatment of a patient with chronic crossed aphasia after severe TBI and long-term coma - Case Report.

    Science.gov (United States)

    Chantsoulis, Marzena; Półrola, Paweł; Góral-Półrola, Jolanta; Hajdukiewicz, Anna; Supiński, Jan; Kropotov, Juri D; Pachalska, Maria

    2017-03-31

     Objective. The study aimed to evaluate the application of ERPs neuromarkers for the assessment and treatment of a patient with chronic crossed aphasia after severe TBI and a long-term coma. An ambidextrous female patient, aged 29, suffered from posttraumatic chronic crossed aphasia, severe TBI and a prolonged coma after a car accident. The patient took part in two differentiated rehabilitation programmes of neurotherapy included 20 sessions of relative beta training and 20 sessions of rTMS; both programmes were combined with behavioural training. The patient was tested 3 times: before the experiment, after completion of programme A, and after completion of programme B. In the 1st recording, the neuromarker of aphasia was found - an excess of the P2 wave over the left temporal area. There was a cognitive control deficit - an excess of omission errors and an increase of RT variability - all indexes of sporadic ADHD. In the 2nd recording, slight improvements in cognitive control, and language functions were found. In the 3rd recording, after the rTMS sessions most of her cognitive dysfunctions had been resolved, including language functions. It should be stressed that the activation (especially the increase in the ERP potential of the right side over the frontal lobe) was found. The neuromarker of aphasia did not change, only the location had slightly moved frontally. The application of ERP neuromarkers assists in the diagnosis, treatment, and academic success of an ambidextrous patient with chronic posttraumatic aphasia and sporadic ADHD. ERPs can be used to assess the functional brain changes induced by neurotherapeutical programmes.

  11. Orbitofrontal cortex contribution to working memory. N-back ERP study

    International Nuclear Information System (INIS)

    Nakao, Yoshiaki; Tamura, Toshiyo; Kodabashi, Atsushi; Fujimoto, Toshiro; Yarita, Masaru

    2011-01-01

    Remarkable progress in cognitive neuroscience has revealed the involvement of the prefrontal cortex and the orbitofrontal cortex in human working memory, but the orbitofrontal cortex is still one of the least understood regions in the human brain. To elucidate the contribution of the orbitofrontal cortex to human working memory, we studied electroencephalography (EEG) P300 activity in n-back task. We elicited early P3 around 300 ms and late P3 around 360 ms of P300 components in n-back event related potentials (ERP). The amplitudes of the respective peaks changed depending on the working memory load (0-back, 1-back, 2-back, 3-back). We used source analysis to evaluate the orbitofrontal cortex in P3 components. A source model was constructed with the sources seeded from fMRI meta-analysis of n-back task and additional sources in the orbitofrontal cortex and the visual cortex estimated with P100 and late P3 components in the n-back ERP. This source model had more than 99% of GOF (goodness of fit) in n-back ERP. It gave us an insight of brain activity at the positions where sources existed. Early P3 was mainly produced by the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex, the inferior parietal lobule, the medial posterior parietal and the visual cortex. Late P3 was mainly produced by the medial premotor, the lateral premotor, the frontal pole and the orbitofrontal cortex. The contribution of the frontal pole and the orbitofrontal cortex had peaks around 390 ms which were later than late P3 component. In this study, the method to evaluate the orbitofrontal cortex activity in n-back ERP was provided. Our results elicited the involvement of the orbitofrontal cortex in late P3 component of n-back ERP. (author)

  12. Offline analysis of context contribution to ERP-based typing BCI performance

    Science.gov (United States)

    Orhan, Umut; Erdogmus, Deniz; Roark, Brian; Oken, Barry; Fried-Oken, Melanie

    2013-12-01

    Objective. We aim to increase the symbol rate of electroencephalography (EEG) based brain-computer interface (BCI) typing systems by utilizing context information. Approach. Event related potentials (ERP) corresponding to a stimulus in EEG can be used to detect the intended target of a person for BCI. This paradigm is widely utilized to build letter-by-letter BCI typing systems. Nevertheless currently available BCI typing systems still require improvement due to low typing speeds. This is mainly due to the reliance on multiple repetitions before making a decision to achieve higher typing accuracy. Another possible approach to increase the speed of typing while not significantly reducing the accuracy of typing is to use additional context information. In this paper, we study the effect of using a language model (LM) as additional evidence for intent detection. Bayesian fusion of an n-gram symbol model with EEG features is proposed, and a specifically regularized discriminant analysis ERP discriminant is used to obtain EEG-based features. The target detection accuracies are rigorously evaluated for varying LM orders, as well as the number of ERP-inducing repetitions. Main results. The results demonstrate that the LMs contribute significantly to letter classification accuracy. For instance, we find that a single-trial ERP detection supported by a 4-gram LM may achieve the same performance as using 3-trial ERP classification for the non-initial letters of words. Significance. Overall, the fusion of evidence from EEG and LMs yields a significant opportunity to increase the symbol rate of a BCI typing system.

  13. Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging.

    Science.gov (United States)

    Davis, Hannah M; Pacheco-Costa, Rafael; Atkinson, Emily G; Brun, Lucas R; Gortazar, Arancha R; Harris, Julia; Hiasa, Masahiro; Bolarinwa, Surajudeen A; Yoneda, Toshiyuki; Ivan, Mircea; Bruzzaniti, Angela; Bellido, Teresita; Plotkin, Lilian I

    2017-06-01

    Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def ) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the pro-survival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFκB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging. © 2017 The Authors. Aging Cell published by the Anatomical Society

  14. Accentra Pharmaceuticals: Thrashing through ERP Systems

    Science.gov (United States)

    Bradds, Nathan; Hills, Emily; Masters, Kelly; Weiss, Kevin; Havelka, Douglas

    2017-01-01

    Implementing and integrating an Enterprise Resource Planning (ERP) system into an organization is an enormous undertaking that requires substantial cash outlays, time commitments, and skilled IT and business personnel. It requires careful and detailed planning, thorough testing and training, and a change management process that creates a…

  15. Memory effects in syntactic ERP tasks

    NARCIS (Netherlands)

    Sabourin, L.L.; Stowe, L.A.

    The study presented here investigated the role of memory in normal sentence processing by looking at ERP effects to normal sentences and sentences containing grammatical violations. Sentences where the critical word was in the middle of the sentence were compared to sentences where the critical word

  16. Spatial and Time Domain Feature of ERP Speller System Extracted via Convolutional Neural Network

    Directory of Open Access Journals (Sweden)

    Jaehong Yoon

    2018-01-01

    Full Text Available Feature of event-related potential (ERP has not been completely understood and illiteracy problem remains unsolved. To this end, P300 peak has been used as the feature of ERP in most brain–computer interface applications, but subjects who do not show such peak are common. Recent development of convolutional neural network provides a way to analyze spatial and temporal features of ERP. Here, we train the convolutional neural network with 2 convolutional layers whose feature maps represented spatial and temporal features of event-related potential. We have found that nonilliterate subjects’ ERP show high correlation between occipital lobe and parietal lobe, whereas illiterate subjects only show correlation between neural activities from frontal lobe and central lobe. The nonilliterates showed peaks in P300, P500, and P700, whereas illiterates mostly showed peaks in around P700. P700 was strong in both subjects. We found that P700 peak may be the key feature of ERP as it appears in both illiterate and nonilliterate subjects.

  17. Enterprise resource planning (ERP) implementation using the value engineering methodology and Six Sigma tools

    Science.gov (United States)

    Leu, Jun-Der; Lee, Larry Jung-Hsing

    2017-09-01

    Enterprise resource planning (ERP) is a software solution that integrates the operational processes of the business functions of an enterprise. However, implementing ERP systems is a complex process. In addition to the technical issues, companies must address problems associated with business process re-engineering, time and budget control, and organisational change. Numerous industrial studies have shown that the failure rate of ERP implementation is high, even for well-designed systems. Thus, ERP projects typically require a clear methodology to support the project execution and effectiveness. In this study, we propose a theoretical model for ERP implementation. The value engineering (VE) method forms the basis of the proposed framework, which integrates Six Sigma tools. The proposed framework encompasses five phases: knowledge generation, analysis, creation, development and execution. In the VE method, potential ERP problems related to software, hardware, consultation and organisation are analysed in a group-decision manner and in relation to value, and Six Sigma tools are applied to avoid any project defects. We validate the feasibility of the proposed model by applying it to an international manufacturing enterprise in Taiwan. The results show improvements in customer response time and operational efficiency in terms of work-in-process and turnover of materials. Based on the evidence from the case study, the theoretical framework is discussed together with the study's limitations and suggestions for future research.

  18. An ERP study on decisions between attractive females and money.

    Science.gov (United States)

    Zeng, Jianmin; Wang, Yujiao; Zhang, Qinglin

    2012-01-01

    To investigate the neural processes of decision-makings between attractive females and money, we recorded 18 male participants' brain event-related potentials (ERPs) when they performed a novel task of deciding between viewing an attractive female's fuzzy picture in clear and gaining a certain amount of money. Two types of attractive females were included: sexy females and beautiful females. Several new electrophysiological discoveries were obtained as following. First, the beautiful females vs. money task (task B) elicited a larger positive ERP deflection (P2) than the sexy females vs. money task (task S) between 290 and 340 ms, and this probably related to the perception matching process between a visual input and an internal representation or expectation. Second, task S evoked greater negative ERP waves (N2) than task B during the time window of 340-390 ms, and this might relate to response conflict and cognitive monitoring for impulsive tendency. Third, the ERP positivity in task S was larger than task B in the time interval of 550-1000 ms, reflecting that sexy female images may have higher decision value for males than beautiful female images. Fourth, compared with choosing to gain money, choosing to view an attractive female evoked a larger late positive component (LPC) during the same time window, possibly because attractive females are more direct and evolutionarily earlier rewards for males than money amounts.

  19. An ERP study on decisions between attractive females and money.

    Directory of Open Access Journals (Sweden)

    Jianmin Zeng

    Full Text Available To investigate the neural processes of decision-makings between attractive females and money, we recorded 18 male participants' brain event-related potentials (ERPs when they performed a novel task of deciding between viewing an attractive female's fuzzy picture in clear and gaining a certain amount of money. Two types of attractive females were included: sexy females and beautiful females. Several new electrophysiological discoveries were obtained as following. First, the beautiful females vs. money task (task B elicited a larger positive ERP deflection (P2 than the sexy females vs. money task (task S between 290 and 340 ms, and this probably related to the perception matching process between a visual input and an internal representation or expectation. Second, task S evoked greater negative ERP waves (N2 than task B during the time window of 340-390 ms, and this might relate to response conflict and cognitive monitoring for impulsive tendency. Third, the ERP positivity in task S was larger than task B in the time interval of 550-1000 ms, reflecting that sexy female images may have higher decision value for males than beautiful female images. Fourth, compared with choosing to gain money, choosing to view an attractive female evoked a larger late positive component (LPC during the same time window, possibly because attractive females are more direct and evolutionarily earlier rewards for males than money amounts.

  20. Measuring Individual Differences in Emotion Regulation: The Emotion Regulation Profile-Revised (ERP-R

    Directory of Open Access Journals (Sweden)

    Delphine Nelis

    2011-02-01

    Full Text Available The main purpose of this study was to validate a new instrument aimed to assess emotion regulation: the Emotion Regulation Profile-Revised (ERP-R. Exploratory factor analyses yielded two theoretically meaningful factors: down-regulation of negative emotions and up-regulation of positive emotions. Internal reliability scores of the two factors were good. Findings showed evidence of convergent/discriminant validity, with ERP-R scores being independent of non verbal reasoning and verbal skills while positively related to emotional intelligence and to relevant personality dimensions. There was also preliminary evidence of criterion validity. ERP-R scores also demonstrated incremental validity to predict a number of criteria over and above emotional intelligence and emotional stability. Overall, the results show a clear 2 factors solution for the ERP-R and high correlations with convergent and divergent scales as well as good criterion and incremental validities.