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Sample records for chin-1 regulate cdc-42

  1. Cdc42 regulates cofilin during the establishment of neuronal polarity

    DEFF Research Database (Denmark)

    Garvalov, Boyan K; Flynn, Kevin C; Neukirchen, Dorothee;

    2007-01-01

    The establishment of polarity is an essential process in early neuronal development. Although a number of molecules controlling neuronal polarity have been identified, genetic evidence about their physiological roles in this process is mostly lacking. We analyzed the consequences of loss of Cdc42......, a central regulator of polarity in multiple systems, on the polarization of mammalian neurons. Genetic ablation of Cdc42 in the brain led to multiple abnormalities, including striking defects in the formation of axonal tracts. Neurons from the Cdc42 null animals sprouted neurites but had a strongly...... suppressed ability to form axons both in vivo and in culture. This was accompanied by disrupted cytoskeletal organization, enlargement of the growth cones, and inhibition of filopodial dynamics. Axon formation in the knock-out neurons was rescued by manipulation of the actin cytoskeleton, indicating that the...

  2. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    International Nuclear Information System (INIS)

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression

  3. Roles of Aspergillus nidulans Cdc42/Rho GTPase regulators in hyphal morphogenesis and development.

    Science.gov (United States)

    Si, Haoyu; Rittenour, William R; Harris, Steven D

    2016-01-01

    The Rho-related family of GTPases are pivotal regulators of morphogenetic processes in diverse eukaryotic organisms. In the filamentous fungi two related members of this family, Cdc42 and Rac1, perform particularly important roles in the establishment and maintenance of hyphal polarity. The activity of these GTPases is tightly controlled by two sets of regulators: guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Despite the importance of Cdc42 and Rac1 in polarized hyphal growth, the morphogenetic functions of their cognate GEFs and GAPs have not been widely characterized in filamentous fungi outside the Saccharomycotina. Here we present a functional analysis of the Aspergillus nidulans homologs of the yeast GEF Cdc24 and the yeast GAP Rga1. We show that Cdc24 is required for the establishment of hyphal polarity and localizes to hyphal tips. We also show that Rga1 is necessary for the suppression of branching in developing conidiophores. During asexual development Rga1 appears to act primarily via Cdc42 and in doing so serves as a critical determinant of conidiophore architecture. Our results provide new insight into the roles of Cdc42 during development in A nidulans. PMID:26932184

  4. CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa.

    Science.gov (United States)

    Lichius, Alexander; Goryachev, Andrew B; Fricker, Mark D; Obara, Boguslaw; Castro-Longoria, Ernestina; Read, Nick D

    2014-05-01

    Cell polarization and fusion are crucial developmental processes that occur in response to intracellular and extracellular signals. Asexual spores (conidia) of the mold Neurospora crassa differentiate two types of polarized cell protrusions, germ tubes and conidial anastomosis tubes (CATs), which exhibit negative and positive chemotropism, respectively. We provide the first evidence that shared and separate functions of the Rho-type GTPases CDC-42 and RAC-1 regulate these opposite chemotropisms. We demonstrate that RAC-1 is essential for CAT formation and cell fusion, whereas CDC-42 is necessary and sufficient for normal germ tube development. Cdc42-Rac-interactive-binding (CRIB) reporters were constructed to exclusively label locally activated GTP-bound GTPases. Time course analyses showed that repositioning of these activated GTPase clusters within germ tube and CAT tip apices controls directional growth in the absence of a tip-localized vesicle supply center (Spitzenkörper). We propose a model in which the local assembly of a plasma-membrane-associated GTPase-PAK-MAPK signaling platform regulates chemoattractant perception and secretion in order to synchronize oscillatory cell-cell communication and directional CAT tip growth. PMID:24790223

  5. The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

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    Anna Kirjavainen

    2015-03-01

    Full Text Available Hair cells of the organ of Corti (OC of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC, a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.

  6. NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in Endothelial Tip Cells

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    Alessandro Fantin

    2015-06-01

    Full Text Available Sprouting blood vessels are led by filopodia-studded endothelial tip cells that respond to angiogenic signals. Mosaic lineage tracing previously revealed that NRP1 is essential for tip cell function, although its mechanistic role in tip cells remains poorly defined. Here, we show that NRP1 is dispensable for genetic tip cell identity. Instead, we find that NRP1 is essential to form the filopodial bursts that distinguish tip cells morphologically from neighboring stalk cells, because it enables the extracellular matrix (ECM-induced activation of CDC42, a key regulator of filopodia formation. Accordingly, NRP1 knockdown and pharmacological CDC42 inhibition similarly impaired filopodia formation in vitro and in developing zebrafish in vivo. During mouse retinal angiogenesis, CDC42 inhibition impaired tip cell and vascular network formation, causing defects that resembled those due to loss of ECM-induced, but not VEGF-induced, NRP1 signaling. We conclude that NRP1 enables ECM-induced filopodia formation for tip cell function during sprouting angiogenesis.

  7. The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface

    DEFF Research Database (Denmark)

    Cappello, Silvia; Attardo, Alessio; Wu, Xunwei; Iwasato, Takuji; Itohara, Shigeyoshi; Wilsch-Bräuninger, Michaela; Eilken, Hanna M; Rieger, Michael A; Schroeder, Timm T; Huttner, Wieland B; Brakebusch, Cord; Götz, Magdalena

    2006-01-01

    fundamental difference between these progenitors. Here we show that the conditional deletion of the small Rho-GTPase cdc42 at different stages of neurogenesis in mouse telencephalon results in an immediate increase in basal mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length...

  8. Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

    International Nuclear Information System (INIS)

    Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm2) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate that

  9. Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Qiaoqiao; Cho, Eunhye [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Yokota, Hiroki [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Na, Sungsoo, E-mail: sungna@iupui.edu [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States)

    2013-04-19

    Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm{sup 2}) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate

  10. Proper Regulation of Cdc42 Activity is Required for Tight Actin Concentration at the Equator during Cytokinesis in Adherent Mammalian Cells

    Science.gov (United States)

    Zhu, Xiaodong; Wang, Junxia; Moriguchi, Kazuki; Liow, Lu Ting; Ahmed, Sohail; Kaverina, Irina; Murata-Hori, Maki

    2012-01-01

    Cytokinesis in mammalian cells requires actin assembly at the equatorial region. Although functions of RhoA in this process have been well established, additional mechanisms are likely involved. We have examined if Cdc42 is involved in actin assembly during cytokinesis. Depletion of Cdc42 had no apparent effects on the duration of cytokinesis, while overexpression of constitutively active Cdc42 (CACdc42) caused cytokinesis failure in normal rat kidney epithelial cells. Cells depleted of Cdc42 displayed abnormal cell morphology and caused a failure of tight accumulation of actin and RhoA at the equator. In contrast, in cells overexpressing CACdc42, actin formed abnormal bundles and RhoA was largely eliminated from the equator. Our results suggest that accurate regulation of Cdc42 activity is crucial for proper equatorial actin assembly and RhoA localization during cytokinesis. Notably, our observations also suggest that tight actin concentration is not essential for cytokinesis in adherent mammalian cells. PMID:21763307

  11. Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

    OpenAIRE

    Benninger, Yves; Thurnherr, Tina; Pereira, Jorge A.; Krause, Sven; Wu, Xunwei; Chrostek-Grashoff, Anna; Herzog, Dominik; Nave, Klaus-Armin; Franklin, Robin J. M.; Meijer, Dies; Brakebusch, Cord; Suter, Ueli; Relvas, João B.

    2007-01-01

    During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is re...

  12. The role of CDC42 in cancer%CDC42与癌症

    Institute of Scientific and Technical Information of China (English)

    徐永茹; 徐平; 徐锋; 李湘萍

    2016-01-01

    Cell division cycle 42 (CDC42)is a member of Rho guanosine triphosphatase (GTPase) family,which plays an important role in cell proliferation , cell migration and cell transformation .The activity of CDC42 can be regulated by guanine nucleotide exchange factors (GEFs),GTPase activating proteins (GAPs) and guanine nucleotide-dissociation inhib-itors (GDIs).Recently,CDC42 has been reported as abnormally expressed in many human cancers ,suggesting that CDC42 performs complex functions in tumorigenesis .Therefore,this paper aims to shed light on the functions of CDC 42 in cancers in terms of the alteration of CDC42 activity,CDC42 regulators,as well as its effectors.%细胞分裂周期蛋白42(cell division cycle 42,CDC42)是Rho蛋白鸟苷三磷酸酶(guanosine triphosphatase, GTPase)家族成员之一,在细胞增殖、迁移、转化等过程发挥重要作用。与大多数GTPase一样,CDC42的活性受到鸟嘌呤核苷酸转换因子( guanine nucleotide exchange factors , GEF )、GTP 酶激活蛋白( GTPase activating proteins , GAP)和鸟苷酸解离抑制因子( guanine nucleotide-dissociation inhibitors ,GDI)的调控。目前研究表明,CDC42在大多数人癌症组织中表达异常,对癌症的发生发展具有复杂而重要的调控作用。该文就CDC42自身活性变化、CDC42调节因子的变化及其下游效应因子的变化在癌症中的作用进行综述,旨在深入理解CDC42在人类癌症中的作用机制。

  13. Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse liver

    DEFF Research Database (Denmark)

    van Hengel, Jolanda; D'Hooge, Petra; Hooghe, Bart;

    2008-01-01

    BACKGROUND & AIMS: The Rho small guanosine triphosphatase Cdc42 is critical for diverse cellular functions, including regulation of actin organization, cell polarity, intracellular membrane trafficking, transcription, cell-cycle progression, and cell transformation. This implies that Cdc42 might be...

  14. miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling

    Science.gov (United States)

    Franke, Kristin; Otto, Wolfgang; Johannes, Sascha; Baumgart, Jan; Nitsch, Robert; Schumacher, Stefan

    2012-01-01

    The small GTPase RhoG plays a central role in actin remodelling during diverse biological processes such as neurite outgrowth, cell migration, phagocytosis of apoptotic cells, and the invasion of pathogenic bacteria. Although it is known that RhoG stimulates neurite outgrowth in the rat pheochromocytoma PC12 cell line, neither the physiological function nor the regulation of this GTPase in neuronal differentiation is clear. Here, we identify RhoG as an inhibitor of neuronal process complexity, which is regulated by the microRNA miR-124. We find that RhoG inhibits dendritic branching in hippocampal neurons in vitro and in vivo. RhoG also inhibits axonal branching, acting via an ELMO/Dock180/Rac1 signalling pathway. However, RhoG inhibits dendritic branching dependent on the small GTPase Cdc42. Finally, we show that the expression of RhoG in neurons is suppressed by the CNS-specific microRNA miR-124 and connect the regulation of RhoG expression by miR-124 to the stimulation of neuronal process complexity. Thus, RhoG emerges as a cellular conductor of Rac1 and Cdc42 activity, in turn regulated by miR-124 to control axonal and dendritic branching. PMID:22588079

  15. Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration

    OpenAIRE

    Bray, Kristi; Gillette, Melissa; Young, Jeanette; Loughran, Elizabeth; Hwang, Melissa; Sears, James Cooper; Vargo-Gogola, Tracy

    2013-01-01

    Introduction The Rho GTPase Cdc42 is overexpressed and hyperactivated in breast tumors compared to normal breast tissue. Cdc42 regulates key processes that are critical for mammary gland morphogenesis and become disrupted during the development, progression, and metastasis of breast cancer. However, the contribution of Cdc42 to normal and neoplastic mammary gland development in vivo remains poorly understood. We were therefore interested in investigating the effects of Cdc42 overexpression on...

  16. Cdc42 promotes host defenses against fatal infection

    DEFF Research Database (Denmark)

    Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V;

    2013-01-01

    The small Rho GTPase, Cdc42, regulates key signaling pathways required for multiple cell functions including maintenance of shape, polarity, proliferation, invasion, migration, differentiation and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we...... attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections that...... were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also...

  17. Opposing Roles for Actin in Cdc42p PolarizationD⃞

    OpenAIRE

    Irazoqui, Javier E.; Howell, Audrey S.; Theesfeld, Chandra L.; Lew, Daniel J.

    2005-01-01

    In animal and fungal cells, the monomeric GTPase Cdc42p is a key regulator of cell polarity that itself exhibits a polarized distribution in asymmetric cells. Previous work showed that in budding yeast, Cdc42p polarization is unaffected by depolymerization of the actin cytoskeleton (Ayscough et al., J. Cell Biol. 137, 399–416, 1997). Surprisingly, we now report that unlike complete actin depolymerization, partial actin depolymerization leads to the dispersal of Cdc42p from the polarization si...

  18. Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Cynthia L Araujo-Palomares

    Full Text Available Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkörper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa.

  19. GIT2 represses Crk- and Rac1-regulated cell spreading and Cdc42-mediated focal adhesion turnover

    OpenAIRE

    Frank, Scott R.; Adelstein, Molly R; Hansen, Steen H.

    2006-01-01

    G protein-coupled receptor kinase interactors (GITs) regulate focal adhesion (FA) turnover, cell spreading, and motility through direct interaction with paxillin and the Rac-exchange factor Pak-interacting exchange factor β (βPIX). However, it is not clear whether GITs function to activate or repress motility or if the predominant GIT forms, GIT1 and GIT2, serve distinct or redundant roles. Here we demonstrate an obligatory role for endogenous GIT2 in repression of lamellipodial extension and...

  20. Rho GTPase protein Cdc42 is critical for postnatal cartilage development.

    Science.gov (United States)

    Nagahama, Ryo; Yamada, Atsushi; Tanaka, Junichi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Yamamoto, Matsuo; Mishima, Kenji; Aiba, Atsu; Maki, Koutaro; Kamijo, Ryutaro

    2016-02-19

    Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 (fl/fl); Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 (fl/fl)) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. PMID:26820532

  1. The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

    International Nuclear Information System (INIS)

    Highlights: ► Regulation of exocytosis by Rho GTPase Cdc42. ► Cdc42 increases the number of fusion events from newly recruited vesicles. ► Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott–Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

  2. Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice

    DEFF Research Database (Denmark)

    Yuan, Haixin; Zhang, Hong; Wu, Xunwei;

    2009-01-01

    Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42 in...... regeneration, which may result from impaired cytoskeletal organization and intracellular trafficking in hepatocytes. Conclusion: Our results revealed important roles of Cdc42 in the regulation of proliferative signaling during liver regeneration....

  3. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    International Nuclear Information System (INIS)

    Highlights: • Cd2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd2+. • DsRNA-suppression of LvCdc42 and MAPKs during Cd2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd2+. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

  4. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-06-15

    Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

  5. The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse

    DEFF Research Database (Denmark)

    Vasyutina, Elena; Martarelli, Benedetta; Brakebusch, Cord; Wende, Hagen; Birchmeier, Carmen

    2009-01-01

    Rac1 and Cdc42 are small G-proteins that regulate actin dynamics and affect plasma membrane protrusion and vesicle traffic. We used conditional mutagenesis in mice to demonstrate that Rac1 and Cdc42 are essential for myoblast fusion in vivo and in vitro. The deficit in fusion of Rac1 or Cdc42...... genetic analysis demonstrates thus that the function of Rac in myoblast fusion is evolutionarily conserved from insects to mammals and that Cdc42, a molecule hitherto not implicated in myoblast fusion, is essential for the fusion of murine myoblasts....

  6. An Essential Role for Cdc42 in the Functioning of the Adult Mammary Gland.

    Science.gov (United States)

    Druso, Joseph E; Endo, Makoto; Lin, Miao-Chong Joy; Peng, Xu; Antonyak, Marc A; Meller, Stephanie; Cerione, Richard A

    2016-04-22

    The Rho family small GTPase Cdc42 has been implicated in a wide range of cellular functions including the establishment of cell polarity and the remodeling of the actin cytoskeletal architecture, resulting in the tight regulation of cell growth and survival during developmental processes. The complete knock-out of Cdc42 in the mouse is embryonic-lethal, and its targeted deletion in various tissues has been shown to disrupt tissue homeostasis. Thus far, in most studies, the targeted deletion of Cdc42 occurred during embryogenesis. Here, we have used a conditional gene deletion strategy in mice to probe the specific role of Cdc42 during adult mammary gland function. Cdc42 conditional-knock-out females were unable to adequately nourish their pups, due to a disorganized epithelial compartment within their mammary glands. A closer examination showed that their mammary epithelial cells were not able to maintain functional alveolar lumens, due to an inability to establish normal apical/basal epithelial polarity, as well as proper cell-cell contacts. Loss of these essential epithelial characteristics led to a premature sloughing off of the Cdc42-null epithelial cells. Overall our findings demonstrate that Cdc42 plays essential roles in mammary gland function post pregnancy, where it helps to establish proper epithelial cell polarity and tissue homeostasis during lactation. PMID:26912661

  7. Opposing Roles for Actin in Cdc42p PolarizationD⃞

    Science.gov (United States)

    Irazoqui, Javier E.; Howell, Audrey S.; Theesfeld, Chandra L.; Lew, Daniel J.

    2005-01-01

    In animal and fungal cells, the monomeric GTPase Cdc42p is a key regulator of cell polarity that itself exhibits a polarized distribution in asymmetric cells. Previous work showed that in budding yeast, Cdc42p polarization is unaffected by depolymerization of the actin cytoskeleton (Ayscough et al., J. Cell Biol. 137, 399–416, 1997). Surprisingly, we now report that unlike complete actin depolymerization, partial actin depolymerization leads to the dispersal of Cdc42p from the polarization site in unbudded cells. We provide evidence that dispersal is due to endocytosis associated with cortical actin patches and that actin cables are required to counteract the dispersal and maintain Cdc42p polarity. Thus, although Cdc42p is initially polarized in an actin-independent manner, maintaining that polarity may involve a reinforcing feedback between Cdc42p and polarized actin cables to counteract the dispersing effects of actin-dependent endocytosis. In addition, we report that once a bud has formed, polarized Cdc42p becomes more resistant to dispersal, revealing an unexpected difference between unbudded and budded cells in the organization of the polarization site. PMID:15616194

  8. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe;

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled...... later for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and...

  9. CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis.

    Science.gov (United States)

    Caron, Christine; DeGeer, Jonathan; Fournier, Patrick; Duquette, Philippe M; Luangrath, Vilayphone; Ishii, Hidetaka; Karimzadeh, Fereshteh; Lamarche-Vane, Nathalie; Royal, Isabelle

    2016-01-01

    Mutations in the CdGAP/ARHGAP31 gene, which encodes a GTPase-activating protein for Rac1 and Cdc42, have been reported causative in the Adams-Oliver developmental syndrome often associated with vascular defects. However, despite its abundant expression in endothelial cells, CdGAP function in the vasculature remains unknown. Here, we show that vascular development is impaired in CdGAP-deficient mouse embryos at E15.5. This is associated with superficial vessel defects and subcutaneous edema, resulting in 44% embryonic/perinatal lethality. VEGF-driven angiogenesis is defective in CdGAP(-/-) mice, showing reduced capillary sprouting from aortic ring explants. Similarly, VEGF-dependent endothelial cell migration and capillary formation are inhibited upon CdGAP knockdown. Mechanistically, CdGAP associates with VEGF receptor-2 and controls VEGF-dependent signaling. Consequently, CdGAP depletion results in impaired VEGF-mediated Rac1 activation and reduced phosphorylation of critical intracellular mediators including Gab1, Akt, PLCγ and SHP2. These findings are the first to demonstrate the importance of CdGAP in embryonic vascular development and VEGF-induced signaling, and highlight CdGAP as a potential therapeutic target to treat pathological angiogenesis and vascular dysfunction. PMID:27270835

  10. Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

    DEFF Research Database (Denmark)

    Pleines, Irina; Dütting, Sebastian; Cherpokova, Deya; Eckly, Anita; Meyer, Imke; Morowski, Martina; Krohne, Georg; Schulze, Harald; Gachet, Christian; Debili, Najet; Brakebusch, Cord Herbert; Nieswandt, Bernhard

    2013-01-01

    and tubulin cytoskeleton. Rho GTPases, such as RhoA, Rac1, and Cdc42, are important regulators of cytoskeletal rearrangements in platelets; however, the specific roles of these proteins during platelet production have not been established. Using conditional knockout mice, we show here that Rac1 and...... Cdc42 possess redundant functions in platelet production and function. In contrast to a single-deficiency of either protein, a double-deficiency of Rac1 and Cdc42 in MKs resulted in macrothrombocytopenia, abnormal platelet morphology, and impaired platelet function. Double-deficient bone marrow MKs...... matured normally in vivo but displayed highly abnormal morphology and uncontrolled fragmentation. Consistently, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in vitro. Strikingly, this phenotype was associated with severely defective tubulin organization, whereas actin assembly and...

  11. Thyroid bud morphogenesis requires CDC42- and SHROOM3-dependent apical constriction

    Science.gov (United States)

    Loebel, David A. F.; Plageman, Timothy F.; Tang, Theresa L.; Jones, Vanessa J.; Muccioli, Maria; Tam, Patrick P. L.

    2016-01-01

    ABSTRACT Early development of the gut endoderm and its subsequent remodeling for the formation of organ buds are accompanied by changes to epithelial cell shape and polarity. Members of the Rho-related family of small GTPases and their interacting proteins play multiple roles in regulating epithelial morphogenesis. In this study we examined the role of Cdc42 in foregut development and organ bud formation. Ablation of Cdc42 in post-gastrulation mouse embryos resulted in a loss of apical-basal cell polarity and columnar epithelial morphology in the ventral pharyngeal endoderm, in conjunction with a loss of apical localization of the known CDC42 effector protein PARD6B. Cell viability but not proliferation in the foregut endoderm was impaired. Outgrowth of the liver, lung and thyroid buds was severely curtailed in Cdc42-deficient embryos. In particular, the thyroid bud epithelium did not display the apical constriction that normally occurs concurrently with the outgrowth of the bud into the underlying mesenchyme. SHROOM3, a protein that interacts with Rho GTPases and promotes apical constriction, was strongly expressed in the thyroid bud and its sub-cellular localization was disrupted in Cdc42-deficient embryos. In Shroom3 gene trap mutant embryos, the thyroid bud epithelium showed no apical constriction, while the bud continued to grow and protruded into the foregut lumen. Our findings indicate that Cdc42 is required for epithelial polarity and organization in the endoderm and for apical constriction in the thyroid bud. It is possible that the function of CDC42 is partly mediated by SHROOM3. PMID:26772200

  12. FLIM FRET Visualization of Cdc42 Activation by Netrin-1 in Embryonic Spinal Commissural Neuron Growth Cones

    Science.gov (United States)

    Rappaz, Benjamin; Lai Wing Sun, Karen; Correia, James P.; Wiseman, Paul W.; Kennedy, Timothy E.

    2016-01-01

    Netrin-1 is an essential extracellular chemoattractant that signals through its receptor DCC to guide commissural axon extension in the embryonic spinal cord. DCC directs the organization of F-actin in growth cones by activating an intracellular protein complex that includes the Rho GTPase Cdc42, a critical regulator of cell polarity and directional migration. To address the spatial distribution of signaling events downstream of netrin-1, we expressed the FRET biosensor Raichu-Cdc42 in cultured embryonic rat spinal commissural neurons. Using FLIM-FRET imaging we detected rapid activation of Cdc42 in neuronal growth cones following application of netrin-1. Investigating the signaling mechanisms that control Cdc42 activation by netrin-1, we demonstrate that netrin-1 rapidly enriches DCC at the leading edge of commissural neuron growth cones and that netrin-1 induced activation of Cdc42 in the growth cone is blocked by inhibiting src family kinase signaling. These findings reveal the activation of Cdc42 in embryonic spinal commissural axon growth cones and support the conclusion that src family kinase activation downstream of DCC is required for Cdc42 activation by netrin-1. PMID:27482713

  13. Podocyte-specific loss of cdc42 leads to congenital nephropathy

    DEFF Research Database (Denmark)

    Scott, Rizaldy P; Hawley, Steve P; Ruston, Julie; Du, Jianmei; Brakebusch, Cord; Jones, Nina; Pawson, Tony

    2012-01-01

    Rho family GTPases are molecular switches best known for their pivotal role in dynamic regulation of the actin cytoskeleton. The prototypic members of this family are Cdc42, Rac1, and RhoA; these GTPases contribute to the breakdown of glomerular filtration and the resultant proteinuria, but their...... functions in normal podocyte physiology remain poorly understood. Here, mice lacking Cdc42 in podocytes developed congenital nephropathy and died as a result of renal failure within 2 weeks after birth. In contrast, mice lacking Rac1 or RhoA in podocytes were overtly normal and lived to adulthood. Kidneys...... from Cdc42-mutant mice exhibited protein-filled microcysts with hallmarks of collapsing glomerulopathy, as well as extensive effacement of podocyte foot processes with abnormal junctional complexes. Furthermore, we observed aberrant expression of several podocyte markers and cell polarity proteins in...

  14. Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

    DEFF Research Database (Denmark)

    Benninger, Yves; Thurnherr, Tina; Pereira, Jorge A;

    2007-01-01

    During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue...

  15. Cdc42 is critical for cartilage development during endochondral ossification.

    Science.gov (United States)

    Suzuki, Wataru; Yamada, Atsushi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Harada, Takeshi; Nakayama, Mutsuko; Nagahama, Ryo; Maki, Koutaro; Takeda, Shu; Yamamoto, Matsuo; Aiba, Atsu; Baba, Kazuyoshi; Kamijo, Ryutaro

    2015-01-01

    Cdc42 is a widely expressed protein that belongs to the family of Rho GTPases and controls a broad variety of signal transduction pathways in a variety of cell types. To investigate the physiological functions of Cdc42 during cartilage development, we generated chondrocyte-specific inactivated Cdc42 mutant mice (Cdc42(fl/fl); Col2-Cre). The gross morphology of mutant neonates showed shorter limbs and body as compared with the control mice (Cdc42(fl/fl)). Skeletal preparations stained with alcian blue and alizarin red also revealed that the body and the long bone length of the mutants were shorter than those of the control mice. Furthermore, severe defects were found in growth plate chondrocytes in the femur sections of mutant mice, characterized by a reduced proliferating zone height, wider hypertrophic zone, and loss of columnar organization in proliferating chondrocytes. The expression levels of chondrocyte marker genes, such as Col2, Col10, and Mmp13, in mutant mice were decreased as compared with the control mice. Mineralization of trabecular bones in the femur sections was also decreased in the mutants as compared with control mice, whereas osteoid volume was increased. Together these results suggested that chondrocyte proliferation and differentiation in growth plates in the present mutant mice were not normally organized, which contributed to abnormal bone formation. We concluded that Cdc42 is essential for cartilage development during endochondral bone formation. PMID:25343271

  16. Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity

    OpenAIRE

    Schlessinger, Karni; McManus, Edward J.; Hall, Alan

    2007-01-01

    Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3β and accumulation of the adenom...

  17. Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

    International Nuclear Information System (INIS)

    localize to lipid rafts and recruit cholesterol into protrusions and away from caveolae, leading to increased phosphorylation of caveolin-1, which inhibits Cdc42-dependent endocytosis. This study provides a new insight for the role for prominins in the regulation of PM lipid organization

  18. Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Raman Deep, E-mail: Takhter.Ramandeep@mayo.edu; Schroeder, Andreas S.; Scheffer, Luana; Holicky, Eileen L.; Wheatley, Christine L.; Marks, David L., E-mail: Marks.david@mayo.edu; Pagano, Richard E.

    2013-05-10

    localize to lipid rafts and recruit cholesterol into protrusions and away from caveolae, leading to increased phosphorylation of caveolin-1, which inhibits Cdc42-dependent endocytosis. This study provides a new insight for the role for prominins in the regulation of PM lipid organization.

  19. P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

    Science.gov (United States)

    Plutoni, Cédric; Bazellieres, Elsa; Le Borgne-Rochet, Maïlys; Comunale, Franck; Brugues, Agusti; Séveno, Martial; Planchon, Damien; Thuault, Sylvie; Morin, Nathalie; Bodin, Stéphane; Trepat, Xavier

    2016-01-01

    Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM. PMID:26783302

  20. Structure and Expression of Several Putative Cdc42-Interacting Proteins in Magnaporthe grisea

    Institute of Scientific and Technical Information of China (English)

    ZHENG Wu; CHEN Ji-sheng; ZHENG Shi-qin; LU Guo-dong; WANG Zong-hua

    2006-01-01

    MgCdc42 (Cdc42 in Magnaporthe grisea), with high homology to ScCdc42 (Cdc42 in Saccharomyces cerevisiae), has been demonstrated to involve in the morphogenesis and infection process. To further understand the signaling network,the putative MgCdc42-interacting proteins were analyzed. ScCdc42-interacting protein sequences were first used to BLAST against the M. grisea genome database to retrieve their corresponding analogs. Subsequently, conserved domains of these proteins were compared and expression patterns of their encoding genes in different MgCdc42 mutation states were analyzed by semiquantitative RT-PCR. All retrieved analogs of ScCdc42-interacting proteins from the M.grisea database have conserved domains as those in S. cerevisiae. Expression of their encoding genes increased in MgCdc42CA mutant and decreased in MgCdc42KO mutant. However, MgBem1, Chm1, and MgGic1 in MgCdc42DN mutant had the same expression level as that in the wild type, although MgBem4, MgBoi2, MgCdc24, MgGic2, MgRga1,and Mst20 had decreased expression level, as expected. Overall, it is concluded that there may exist a similar Cdc42 signal pathway in M. grisea as in S. cerevisiae and MgCdc42 plays a key role in the pathway.

  1. Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

    DEFF Research Database (Denmark)

    Blattner, Simone M; Hodgin, Jeffrey B; Nishio, Masashi;

    2013-01-01

    the regulation of actin cytoskeleton dynamics. Here, we employed podocyte-specific Cre-lox technology and found that mice with deletion of Rac1 display normal podocyte morphology without glomerular dysfunction well into adulthood. Using the protamine sulfate model of acute podocyte injury, podocyte...... steady state. However, Rac1 has either beneficial or deleterious effects depending on the context of podocyte impairment. Thus, our study highlights the divergent roles of Rac1 and Cdc42 function in podocyte maintenance and injury.Kidney International advance online publication, 15 May 2013; doi:10...

  2. FMNL2 drives actin-based protrusion and migration downstream of Cdc42

    DEFF Research Database (Denmark)

    Block, Jennifer; Breitsprecher, Dennis; Kühn, Sonja;

    2012-01-01

    -guanosine triphosphatase Cdc42. Abolition of myristoylation or Cdc42 binding interferes with proper FMNL2 activation, constituting an essential prerequisite for subcellular targeting. In vitro, C-terminal FMNL2 drives elongation rather than nucleation of actin filaments in the presence of profilin. In addition, filament...... establish that the FMNL subfamily member FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia....

  3. Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p

    OpenAIRE

    Gladfelter, Amy S.; Bose, Indrani; Zyla, Trevin R.; Bardes, Elaine S.G.; Lew, Daniel J.

    2002-01-01

    At the beginning of the budding yeast cell cycle, the GTPase Cdc42p promotes the assembly of a ring of septins at the site of future bud emergence. Here, we present an analysis of cdc42 mutants that display specific defects in septin organization, which identifies an important role for GTP hydrolysis by Cdc42p in the assembly of the septin ring. The mutants show defects in basal or stimulated GTP hydrolysis, and the septin misorganization is suppressed by overexpression of a Cdc42p GTPase-act...

  4. Cdc42 and Rac1 activity is reduced in human pheochromocytoma and correlates with FARP1 and ARHGEF1 expression.

    Science.gov (United States)

    Croisé, Pauline; Houy, Sébastien; Gand, Mathieu; Lanoix, Joël; Calco, Valérie; Tóth, Petra; Brunaud, Laurent; Lomazzi, Sandra; Paramithiotis, Eustache; Chelsky, Daniel; Ory, Stéphane; Gasman, Stéphane

    2016-04-01

    Among small GTPases from the Rho family, Cdc42, RAC, and Rho are well known to mediate a large variety of cellular processes linked with cancer biology through their ability to cycle between an inactive (GDP-bound) and an active (GTP-bound) state. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP to generate the activated form, whereas the GTPase-activating proteins (GAPs) catalyze GTP hydrolysis, leading to the inactivated form. Modulation of Rho GTPase activity following altered expression of RHO-GEFs and/or RHO-GAPs has already been reported in various human tumors. However, nothing is known about the Rho GTPase activity or the expression of their regulators in human pheochromocytomas, a neuroendocrine tumor (NET) arising from chromaffin cells of the adrenal medulla. In this study, we demonstrate, through an ELISA-based activity assay, that Rac1 and Cdc42 activities decrease in human pheochromocytomas (PCCs) compared with the matched adjacent non-tumor tissue. Furthermore, through quantitative mass spectrometry (MS) approaches, we show that the expression of two RHO-GEF proteins, namely ARHGEF1 and FARP1, is significantly reduced in tumors compared with matched non-tumor tissue, whereas ARHGAP36 expression is increased. Moreover, siRNA-based knockdown of ARHGEF1 and FARP1 in PC12 cells leads to a significant inhibition of Rac1 and Cdc42 activities, respectively. Finally, a principal component analysis (PCA) of our dataset was able to discriminate PCC from non-tumor tissue and indicates a close correlation between Cdc42/Rac1 activity and FARP1/ARHGEF1 expression. Altogether, our findings reveal for the first time the importance of modulation of Rho GTPase activities and expression of their regulators in human PCCs. PMID:26911374

  5. Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Romain Ferru-Clément

    Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR is a chloride channel that is expressed on the apical plasma membrane (PM of epithelial cells. The most common deleterious allele encodes a trafficking-defective mutant protein undergoing endoplasmic reticulum-associated degradation (ERAD and presenting lower PM stability. In this study, we investigated the involvement of the Cdc42 pathway in CFTR turnover and trafficking in a human bronchiolar epithelial cell line (CFBE41o- expressing wild-type CFTR. Cdc42 is a small GTPase of the Rho family that fulfils numerous cell functions, one of which is endocytosis and recycling process via actin cytoskeleton remodelling. When we treated cells with chemical inhibitors such as ML141 against Cdc42 and wiskostatin against the downstream effector N-WASP, we observed that CFTR channel activity was inhibited, in correlation with a decrease in CFTR amount at the cell surface and an increase in dynamin-dependent CFTR endocytosis. Anchoring of CFTR to the cortical cytoskeleton was then presumably impaired by actin disorganization. When we performed siRNA-mediated depletion of Cdc42, actin polymerization was not impacted, but we observed actin-independent consequences upon CFTR. Total and PM CFTR amounts were increased, resulting in greater activation of CFTR. Pulse-chase experiments showed that while CFTR degradation was slowed, CFTR maturation through the Golgi apparatus remained unaffected. In addition, we observed increased stability of CFTR in PM and reduction of its endocytosis. This study highlights the involvement of the Cdc42 pathway at several levels of CFTR biogenesis and trafficking: (i Cdc42 is implicated in the first steps of CFTR biosynthesis and processing; (ii it contributes to the stability of CFTR in PM via its anchoring to cortical actin; (iii it promotes CFTR endocytosis and presumably its sorting toward lysosomal degradation.

  6. Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway

    Science.gov (United States)

    Simon, Sylvia; Schell, Ursula; Heuer, Natalie; Hager, Dominik; Albers, Michael F.; Matthias, Jan; Fahrnbauer, Felix; Trauner, Dirk; Eichinger, Ludwig; Hedberg, Christian; Hilbi, Hubert

    2015-01-01

    Small molecule signaling promotes the communication between bacteria as well as between bacteria and eukaryotes. The opportunistic pathogenic bacterium Legionella pneumophila employs LAI-1 (3-hydroxypentadecane-4-one) for bacterial cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, which regulates a variety of processes including natural competence for DNA uptake and pathogen-host cell interactions. In this study, we analyze the role of LAI-1 in inter-kingdom signaling. L. pneumophila lacking the autoinducer synthase LqsA no longer impeded the migration of infected cells, and the defect was complemented by plasmid-borne lqsA. Synthetic LAI-1 dose-dependently inhibited cell migration, without affecting bacterial uptake or cytotoxicity. The forward migration index but not the velocity of LAI-1-treated cells was reduced, and the cell cytoskeleton appeared destabilized. LAI-1-dependent inhibition of cell migration involved the scaffold protein IQGAP1, the small GTPase Cdc42 as well as the Cdc42-specific guanine nucleotide exchange factor ARHGEF9, but not other modulators of Cdc42, or RhoA, Rac1 or Ran GTPase. Upon treatment with LAI-1, Cdc42 was inactivated and IQGAP1 redistributed to the cell cortex regardless of whether Cdc42 was present or not. Furthermore, LAI-1 reversed the inhibition of cell migration by L. pneumophila, suggesting that the compound and the bacteria antagonistically target host signaling pathway(s). Collectively, the results indicate that the L. pneumophila quorum sensing compound LAI-1 modulates migration of eukaryotic cells through a signaling pathway involving IQGAP1, Cdc42 and ARHGEF9. PMID:26633832

  7. Cdc42 expression in keratinocytes is required for the maintenance of the basement membrane in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Brakebusch, Cord

    2006-01-01

    , structure and number of hemidesomosomes were not significantly changed in the Cdc42 mutant skin compared with the control mice and no blister formation was observed in mutant skin. These data indicate that Cdc42 in keratinocytes is important for maintenance of the basement membrane of skin....

  8. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta; Hagedorn, Ina; Eliautou, Sandra; Bender, Markus; Wu, Xunwei; Lanza, Francois; Gachet, Christian; Brakebusch, Cord; Nieswandt, Bernhard

    2010-01-01

    (ADP)/adenosine triphosphate (ATP) content, increased aggregation at low agonist concentrations, and enhanced aggregate formation on collagen under flow. In vivo, lack of Cdc42 resulted in faster occlusion of ferric chloride-injured arterioles. The life span of Cdc42-deficient platelets was markedly...

  9. Cdc42 Controls Vascular Network Assembly Through Protein Kinase C{iota} During Embryonic Vasculogenesis

    DEFF Research Database (Denmark)

    Qi, Yanmei; Liu, Jie; Wu, Xunwei; Brakebusch, Cord; Leitges, Michael; Han, Yaling; Corbett, Siobhan A; Lowry, Stephen F; Graham, Alan M; Li, Shaohua

    2011-01-01

    The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms.......The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms....

  10. Glucose-stimulated Cdc42 Signaling Is Essential for the Second Phase of Insulin Secretion*

    OpenAIRE

    Wang, Zhanxiang; Oh, Eunjin; Thurmond, Debbie C.

    2007-01-01

    The small Rho family GTPases Cdc42 and Rac1 have each been shown to function in insulin exocytosis and are presumed to function in actin remodeling and insulin granule mobilization. However, whether either GTPase is required for the mobilization phase of insulin release (second phase) and are linked in a common signaling pathway has remained unknown. Here we demonstrate that small interfering RNA-mediated depletion of Cdc42 from isolated islets results in the selective loss of second-phase in...

  11. Dynamics of Cdc42 network embodies a Turing-type mechanism of yeast cell polarity.

    Science.gov (United States)

    Goryachev, Andrew B; Pokhilko, Alexandra V

    2008-04-30

    Complex biochemical networks can be understood by identifying their principal regulatory motifs and mode of action. We model the early phase of budding yeast cellular polarization and show that the biochemical processes in the presumptive bud site comprise a Turing-type mechanism. The roles of the prototypical activator and substrate are played by GTPase Cdc42 in its active and inactive states, respectively. We demonstrate that the nucleotide cycling of Cdc42 converts cellular energy into a stable cluster of activated Cdc42. This energy drives a continuous membrane-cytoplasmic exchange of the cluster components to counteract diffusive spread of the cluster. This exchange explains why only one bud forms per cell cycle, because the winner-takes-all competition of candidate sites inevitably selects a single site. PMID:18381072

  12. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore;

    2005-01-01

    of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the...

  13. Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood

    DEFF Research Database (Denmark)

    Anttonen, Tommi; Kirjavainen, Anna; Belevich, Ilya;

    2012-01-01

    of a basolateral membrane protein in the apical domain were observed. These defects and changes in aPKCλ/ι expression suggested that apical polarization is impaired. Following a lesion at adulthood, supporting cells with Cdc42 loss-induced maturational defects collapsed and failed to remodel F...

  14. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine;

    2006-01-01

    Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of beta-catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3beta. Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial for...

  15. The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

    OpenAIRE

    Kokkoris K.; Gallo Castro D.; Martin S.G.

    2014-01-01

    Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) cataly...

  16. Genetic deletion of cdc42 reveals a crucial role for astrocyte recruitment to the injury site in vitro and in vivo

    DEFF Research Database (Denmark)

    Robel, Stefanie; Bardehle, Sophia; Lepier, Alexandra; Brakebusch, Cord; Götz, Magdalena

    2011-01-01

    signals, the small RhoGTPase Cdc42, selectively in mouse astrocytes in vitro and in vivo. We used an in vitro scratch assay as a minimal wounding model and found that astrocytes lacking Cdc42 (Cdc42Δ) were still able to form protrusions, although in a nonoriented way. Consequently, they failed to migrate...... in a directed manner toward the scratch. When animals were injured in vivo through a stab wound, Cdc42Δ astrocytes developed protrusions properly oriented toward the lesion, but the number of astrocytes recruited to the lesion site was significantly reduced. Surprisingly, however, lesions in Cdc42Δ...

  17. Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts.

    Science.gov (United States)

    Lebensohn, Andres M; Ma, Le; Ho, Hsin-Yi Henry; Kirschner, Marc W

    2006-01-01

    Xenopus egg cytoplasmic extracts have been used to study a variety of complex cellular processes. Given their amenability to biochemical manipulation and physiological balance of regulatory proteins, these extracts are an ideal system to dissect signal transduction pathways leading to actin assembly. We have developed methods to study Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts. In this chapter, we describe detailed procedures to prepare Xenopus egg extracts, Cdc42, and PI(4,5)P2 for use in actin assembly experiments. We also describe a fluorometric pyrene actin assay for quantitative kinetic analysis of actin polymerization and a microscopic rhodamine actin assay for quick measurement of actin rearrangements in extracts. Finally we provide a protocol for immunodepletion of proteins and discuss the use of immunodepletion and rescue experiments for functional analysis of components in the extracts. PMID:16472657

  18. Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Lieven, Oliver; Mamidi, Anant;

    2014-01-01

    Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiat......Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to...... differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell...

  19. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation

    OpenAIRE

    Mahajan, Nupam P.; Liu, Yuanbo; Majumder, Samarpan; Warren, Maria R.; Parker, Carol E.; Mohler, James L.; Earp, H. Shelton; Whang, Young E.

    2007-01-01

    Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. Here we provide the molecular basis for interplay between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen-independent growth o...

  20. GRP75 upregulates clathrin-independent endocytosis through actin cytoskeleton reorganization mediated by the concurrent activation of Cdc42 and RhoA.

    Science.gov (United States)

    Chen, Hang; Gao, Zhihui; He, Changzheng; Xiang, Rong; van Kuppevelt, Toin H; Belting, Mattias; Zhang, Sihe

    2016-05-01

    Therapeutic macromolecules are internalized into the cell by either clathrin-mediated endocytosis (CME) or clathrin-independent endocytosis (CIE). Although some chaperone proteins play an essential role in CME (e.g. Hsc70 in clathrin uncoating), relatively few of these proteins are functionally involved in CIE. We previously revealed a role for the mitochondrial chaperone protein GRP75 in heparan sulfate proteoglycan (HSPG)-mediated, membrane raft-associated macromolecule endocytosis. However, the mechanism underlying this process remains unclear. In this study, using a mitochondrial signal peptide-directed protein trafficking expression strategy, we demonstrate that wild-type GRP75 expression enhanced the uptakes of HSPG and CIE marker cholera toxin B subunit but impaired the uptake of CME marker transferrin. The endocytosis regulation function of GRP75 is largely mediated by its subcellular location in mitochondria and is essentially determined by its ATPase domain. Interestingly, the mitochondrial expression of GRP75 or its ATPase domain significantly stimulates increases in both RhoA and Cdc42 activation, remarkably induces stress fibers and enhances filopodia formation, which collectively results in the promotion of CIE, but the inhibition of CME. Furthermore, silencing of Cdc42 or RhoA impaired the ability of GRP75 overexpression to increase CIE. Therefore, these results suggest that endocytosis vesicle enrichment of GRP75 by mitochondria trafficking upregulates CIE through an actin cytoskeleton reorganization mechanism mediated by the concurrent activation of Cdc42 and RhoA. This finding provides novel insight into organelle-derived chaperone signaling and the regulation of different endocytosis pathways in cells. PMID:27090015

  1. GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis

    OpenAIRE

    Chang, Jeng-Shou; Su, Chia-Yi; Yu, Wen-Hsuan; Lee, Wei-Jiunn; Liu, Yu-Peng; Lai, Tsung-Ching; Jan, Yi-Hua; Yang, Yi-Fang; Shen, Chia-Ning; Shew, Jin-Yuh; Lu, Jean; Yang, Chih-Jen; Huang, Ming-Shyan; Lu, Pei-Jung; Lin, Yuan-Feng

    2015-01-01

    G-protein-coupled receptor kinase interacting protein 1 (GIT1) is participated in cell movement activation, which is a fundamental process during tissue development and cancer progression. GIT1/PIX forming a functional protein complex that contributes to Rac1/Cdc42 activation, resulting in increasing cell mobility. Although the importance of Rac1/Cdc42 activation is well documented in cancer aggressiveness, the clinical importance of GIT1 remains largely unknown. Here, we investigated the cli...

  2. Systems-wide Analysis of K-Ras, Cdc42, and PAK4 Signaling by Quantitative Phosphoproteomics*

    OpenAIRE

    Gnad, Florian; Young, Amy; Zhou, Wei; Lyle, Karen; Ong, Christy C.; Matthew P. Stokes; Silva, Jeffrey C.; Belvin, Marcia; Friedman, Lori S.; Koeppen, Hartmut; Minden, Audrey; Hoeflich, Klaus P.

    2013-01-01

    Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively examine the spectrum of phosphorylation-mediated signaling downstream of each of these key signaling nodes. In this study, we completed a label-free quantitative analysis of oncogenic K-Ras, activated Cdc42, and PAK4-mediated phosphorylation signaling, and report relative quantitation of 2152 phosphorylated peptides on 1062 proteins. We define the overlap in phosphop...

  3. MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process.

    Science.gov (United States)

    Yuan, Jinxian; Huang, Hao; Zhou, Xin; Liu, Xi; Ou, Shu; Xu, Tao; Li, Ruohan; Ma, Limin; Chen, Yangmei

    2016-01-01

    Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing miR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of miR-132 in vivo and found that silencing miR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing miR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing miR-132 may suppress spontaneous seizure activity through the miR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, miR-132 may serve as a potential target for the development of antiepileptic drugs. PMID:27579184

  4. MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process

    Science.gov (United States)

    Huang, Hao; Zhou, Xin; Liu, Xi; Xu, Tao; Ma, Limin

    2016-01-01

    Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing miR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of miR-132 in vivo and found that silencing miR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing miR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing miR-132 may suppress spontaneous seizure activity through the miR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, miR-132 may serve as a potential target for the development of antiepileptic drugs.

  5. Biochemical analysis of the interactions of IQGAP1 C-terminal domain with CDC42

    Institute of Scientific and Technical Information of China (English)

    Sarah; F; Elliott; George; Allen; David; J; Timson

    2012-01-01

    AIM:To understand the interaction of human IQGAP1 and CDC42,especially the effects of phosphorylation and a cancer-associated mutation. METHODS:Recombinant CDC42 and a novel C-termi- nal fragment of IQGAP1 were expressed in,and puri- fied from,Escherichia coli.Site directed mutagenesis was used to create coding sequences for three phos- phomimicking variants(S1441E,S1443D and S1441E/ S1443D)and to recapitulate a cancer-associated mu- tation(M1231I).These variant proteins were also ex- pressed and purified.Protein-protein crosslinking using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide was used to investigate interactions between the C-terminal fragment and CDC42.These interactions were quanti- fied using surface plasmon resonance measurements.Molecular modelling was employed to make predictions about changes to the structure and flexibility of the protein which occur in the cancer-associated variant. RESULTS:The novel,C-terminal region of human IQGAP1 (residues 877-1558)is soluble following expression and purification.It is also capable of binding to CDC42,as judged by crosslinking experiments.Interaction appears to be strongest in the presence of added GTP.The three phosphomimicking mutants had different affini- ties for CDC42.S1441E had an approximately 200-fold reduction in affinity compared to wild type.This was caused largely by a dramatic reduction in the associa- tion rate constant.In contrast,both S1443D and the double variant S1441E/S1443D had similar affinities to the wild type.The cancer-associated variant,M1231I, also had a similar affinity to wild type.However,in the case of this variant,both the association and dis- sociation rate constants were reduced approximately 10-fold.Molecular modelling of the M1231I variant, based on the published crystal structure of part of the C-terminal region,revealed no gross structural changes compared to wild type(root mean square deviation of 0.564over 5556 equivalent atoms).However,pre- dictions of the

  6. Specific deletion of Cdc42 does not affect meiotic spindle organization/migration and homologous chromosome segregation but disrupts polarity establishment and cytokinesis in mouse oocytes

    DEFF Research Database (Denmark)

    Wang, Zhen-Bo; Jiang, Zong-Zhe; Zhang, Qing-Hua;

    2013-01-01

    female infertility in mice. Cdc42 deletion has little effect on meiotic spindle organization and migration to the cortex but inhibits polar body emission, although homologous chromosome segregation occurs. The failure of cytokinesis is due to the loss of polarized Arp2/3 accumulation and actin cap...... polarized actin cap and oocyte polarity, and it determines asymmetric divisions resulting in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional knockout technology. We find that Cdc42 deletion causes...

  7. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways

    DEFF Research Database (Denmark)

    Bosse, Tanja; Ehinger, Julia; Czuchra, Aleksandra;

    2007-01-01

    Activation of c-Met, the hepatocyte growth factor (HGF)/scatter factor receptor induces reorganization of the actin cytoskeleton, which drives epithelial cell scattering and motility and is exploited by pathogenic Listeria monocytogenes to invade nonepithelial cells. However, the precise...... required the simultaneous inactivation of both Cdc42 and PI3-kinase signaling. Moreover, Cdc42 activation was fully independent of PI3-kinase activity, whereas the latter partly depended on Cdc42. Finally, Cdc42 function did not require its interaction with the actin nucleation-promoting factor N...

  8. Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

    DEFF Research Database (Denmark)

    Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli;

    2013-01-01

    The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

  9. Cdc42 and k-Ras Control Endothelial Tubulogenesis through Apical Membrane and Cytoskeletal Polarization: Novel Stimulatory Roles for GTPase Effectors, the Small GTPases, Rac2 and Rap1b, and Inhibitory Influence of Arhgap31 and Rasa1.

    Directory of Open Access Journals (Sweden)

    Pieter R Norden

    Full Text Available A critical and understudied property of endothelial cells is their ability to form lumens and tube networks. Although considerable information has been obtained concerning these issues, including the role of Cdc42 and Rac1 and their effectors such as Pak2, Pak4, Par6b, and co-regulators such as integrins, MT1-MMP and Par3; many key questions remain that are necessary to elucidate molecular and signaling requirements for this fundamental process. In this work, we identify new small GTPase regulators of EC tubulogenesis including k-Ras, Rac2 and Rap1b that act in conjunction with Cdc42 as well as the key downstream effectors, IQGAP1, MRCKβ, beta-Pix, GIT1, and Rasip1 (which can assemble into multiprotein complexes with key regulators including α2β1 integrin and MT1-MMP. In addition, we identify the negative regulators, Arhgap31 (by inactivating Cdc42 and Rac and Rasa1 (by inactivating k-Ras and the positive regulator, Arhgap29 (by inactivating RhoA which play a major functional role during the EC tubulogenic process. Human EC siRNA suppression or mouse knockout of Rasip1 leads to identical phenotypes where ECs form extensive cord networks, but cannot generate lumens or tubes. Essential roles for these molecules during EC tubulogenesis include; i establishment of asymmetric EC cytoskeletal polarization (subapical distribution of acetylated tubulin and basal membrane distribution of F-actin; and ii directed membrane trafficking of pinocytic vacuoles or other intracellular vesicles along acetylated tubulin tracks to the developing apical membrane surface. Cdc42 co-localizes subapically with acetylated tubulin, while Rac1 and k-Ras strongly label vacuole/ vesicle membranes which accumulate and fuse together in a polarized, perinuclear manner. We observe polarized apical membrane and subapical accumulation of key GTPases and effectors regulating EC lumen formation including Cdc42, Rac1, Rac2, k-Ras, Rap1b, activated c-Raf and Rasip1 to control EC

  10. Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1

    DEFF Research Database (Denmark)

    Du, Dan; Pedersen, Esben; Wang, Zhipeng;

    2008-01-01

    -deficient immortalized and primary keratinocytes form only punctate primordial cell contacts in vitro, which cannot mature into belt-like junctions. This defect was independent of enhanced degradation of beta-catenin, but correlated to an impaired activation and localization of aPKCzeta in the Cdc42-null...

  11. Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice

    DEFF Research Database (Denmark)

    Sakamori, Ryotaro; Das, Soumyashree; Yu, Shiyan; Feng, Shanshan; Stypulkowski, Ewa; Guan, Yinzheng; Douard, Veronique; Tang, Waixing; Ferraris, Ronaldo P; Harada, Akihiro; Brakebusch, Cord; Guo, Wei; Gao, Nan

    2012-01-01

    reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells...

  12. Cdc42 Effector Protein 2 (XCEP2 is required for normal gastrulation and contributes to cellular adhesion in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Nelson Richard W

    2004-10-01

    Full Text Available Abstract Background Rho GTPases and their downstream effector proteins regulate a diverse array of cellular processes during embryonic development, including reorganization of cytoskeletal architecture, cell adhesion, and transcription. Changes in the activation state of Rho GTPases are converted into changes in cellular behavior by a diversity of effector proteins, which are activated in response to changes in the GTP binding state of Rho GTPases. In this study we characterize the expression and function of one such effector, XCEP2, that is present during gastrulation stages in Xenopus laevis. Results In a search for genes whose expression is regulated during early stages of embryonic development in Xenopus laevis, a gene encoding a Rho GTPase effector protein (Xenopus Cdc42 effector protein 2, or XCEP2 was isolated, and found to be highly homologous, but not identical, to a Xenopus sequence previously submitted to the Genbank database. These two gene sequences are likely pseudoalleles. XCEP2 mRNA is expressed at constant levels until mid- to late- gastrula stages, and then strongly down-regulated at late gastrula/early neurula stages. Injection of antisense morpholino oligonucleotides directed at one or both pseudoalleles resulted in a significant delay in blastopore closure and interfered with normal embryonic elongation, suggesting a role for XCEP2 in regulating gastrulation movements. The morpholino antisense effect could be rescued by co-injection with a morpholino-insensitive version of the XCEP2 mRNA. Antisense morpholino oligonucleotides were found to have no effect on mesodermal induction, suggesting that the observed effects were due to changes in the behavior of involuting cells, rather than alterations in their identity. XCEP2 antisense morpholino oligonucleotides were also observed to cause complete disaggregation of cells composing animal cap explants, suggesting a specific role of XCEP2 in maintenance or regulation of cell

  13. Rif-mDia1 Interaction Is Involved in Filopodium Formation Independent of Cdc42 and Rac Effectors

    OpenAIRE

    Goh, Wah Ing; Sudhaharan, Thankiah; Lim, Kim Buay; Sem, Kai Ping; Lau, Chew Ling; Ahmed, Sohail

    2011-01-01

    Filopodia are cellular protrusions important for axon guidance, embryonic development, and wound healing. The Rho GTPase Cdc42 is the best studied inducer of filopodium formation, and several of its effectors and their interacting partners have been linked to the process. These include IRSp53, N-WASP, Mena, and Eps8. The Rho GTPase, Rif, also drives filopodium formation. The signaling pathway by which Rif induces filopodia is poorly understood, with mDia2 being the only protein implicated to ...

  14. The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2

    LENUS (Irish Health Repository)

    Krause-Gruszczynska, Malgorzata

    2011-12-28

    Abstract Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-\\/-, integrin-beta1-\\/-, focal adhesion kinase (FAK)-\\/- and Src\\/Yes\\/Fyn-\\/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1\\/2-\\/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker

  15. Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway

    International Nuclear Information System (INIS)

    Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells

  16. A comprehensive genome-wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants.

    Science.gov (United States)

    Vaysse, Amaury; Fang, Shenying; Brossard, Myriam; Wei, Qingyi; Chen, Wei V; Mohamdi, Hamida; Vincent-Fetita, Lynda; Margaritte-Jeannin, Patricia; Lavielle, Nolwenn; Maubec, Eve; Lathrop, Mark; Avril, Marie-Françoise; Amos, Christopher I; Lee, Jeffrey E; Demenais, Florence

    2016-11-01

    Breslow thickness (BT) is a major prognostic factor of cutaneous melanoma (CM), the most fatal skin cancer. The genetic component of BT has only been explored by candidate gene studies with inconsistent results. Our objective was to uncover the genetic factors underlying BT using an hypothesis-free genome-wide approach. Our analysis strategy integrated a genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) for BT followed by pathway analysis of GWAS outcomes using the gene-set enrichment analysis (GSEA) method and epistasis analysis within BT-associated pathways. This strategy was applied to two large CM datasets with Hapmap3-imputed SNP data: the French MELARISK study for discovery (966 cases) and the MD Anderson Cancer Center study (1,546 cases) for replication. While no marginal effect of individual SNPs was revealed through GWAS, three pathways, defined by gene ontology (GO) categories were significantly enriched in genes associated with BT (false discovery rate ≤5% in both studies): hormone activity, cytokine activity and myeloid cell differentiation. Epistasis analysis, within each significant GO, identified a statistically significant interaction between CDC42 and SCIN SNPs (pmeta-int =2.2 × 10(-6) , which met the overall multiple-testing corrected threshold of 2.5 × 10(-6) ). These two SNPs (and proxies) are strongly associated with CDC42 and SCIN gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, a key mechanism underlying melanoma cell migration and invasion. PMID:27347659

  17. Integrin α PAT-2/CDC-42 signaling is required for muscle-mediated clearance of apoptotic cells in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Hsiao-Han Hsieh

    Full Text Available Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2-mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180/CED-12 (ELMO or CED-6 (GULP respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level.

  18. Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

    Directory of Open Access Journals (Sweden)

    Nils Bohmer

    2015-01-01

    Full Text Available Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs and silica-coated iron oxide nanoparticles (SCIONs between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

  19. RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42

    OpenAIRE

    Misselwitz, Benjamin; Dilling, Sabrina; Vonaesch, Pascale; Sacher, Raphael; Snijder, Berend; Schlumberger, Markus; Rout, Samuel; Stark, Manuel; Mering, Christian von; Pelkmans, Lucas; Hardt, Wolf-Dietrich

    2011-01-01

    Pathogens are not only a menace to public health, but they also provide excellent tools for probing host cell function. Thus, studying infection mechanisms has fueled progress in cell biology (Ridley et al, 1992; Welch et al, 1997). In the presented study, we have performed an RNAi screen to identify host cell genes required for Salmonella host cell invasion. This screen identified proteins known to contribute to Salmonella-induced actin rearrangements (e.g., Cdc42 and the Arp2/3 complex; rev...

  20. Mum, this bud’s for you: where do you want it? Roles for Cdc42 in controlling bud site selection in Saccharomyces cerevisiae

    OpenAIRE

    Nelson, W. James

    2003-01-01

    The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,(1,2) but a recent paper has also raised questions about how control of Cdc42 activity is integrated into a propose...

  1. 慢性脑缺血大鼠海马区Cdc42表达及其与认知功能障碍的相关性%Expression Cdc42 protein in hippocampus of chronic cerebral ischemia rat and the relationship with cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    李星; 张博爱; 姬亚杰; 刘荣丽; 贾贺; 张小敏; 刘宇

    2012-01-01

    目的 研究慢性脑缺血大鼠海马组织中细胞分裂周期蛋白42(Cdc42)表达的变化,探讨其在慢性脑缺血所致认知功能障碍中可能发挥的作用.方法 大鼠40只,随机分为假手术组、持久性双侧颈总动脉结扎(2VO)8、10、12w组,每组各10只.应用Morris水迷宫检测大鼠学习记忆能力,用免疫组织化学及Western印迹两种方法检测各组大鼠海马区Cdc42的表达.结果 Morris水迷宫显示手术组大鼠较假手术组大鼠逃避潜伏期明显延长(P<0.05);免疫组化及Western印迹均显示手术组大鼠海马区Cdc42表达明显低于假手术组(P<0.05).结论 Cdc42表达量的降低可能参与了慢性脑缺血所致认知功能障碍的形成.%Objective To investigate the expression of cell division cycle 42 GTP-binding protein (Cdc42) in hippocampus of chronic cerebral hypoperfusion rats model and explore the relationship between Cdc42 protein and cognitive impairment Methods 40 rats were equally divided into sham and 2-VO model groups (permanent ligation of bilateral common carotid arteries for 8, 10 and 12 weeks,respectively). The brains were taken at week 8,10 and 12 after the establishment of models for measuring the expression of Cdc42 protein using Western blotting and immunohistochemistry, cognitive function including learning and memory capacity in rats was evaluated by Morris water maze at the same time after cerebral ischemia. Results In the Morris water maze, the latency of model rats obviously extended compared to that of control rats (P < 0. 05), immunohistochemistry and Western blot all found that the expression of Cdc42 on hippocampal areas in the model rats was significantly decreased than that in control rats (P < 0. 05). Conclusions Low expression of Cdc42 in the hippocampus may play an important role in cognitive dysfunction induced by chronic cerebral ischemia.

  2. Gene 33/Mig-6, a Transcriptionally Inducible Adapter Protein That Binds GTP-Cdc42 and Activates SAPK/JNK*

    Science.gov (United States)

    Makkinje, Anthony; Quinn, Deborah A.; Chen, Ang; Cadilla, Carmen L.; Force, Thomas; Bonventre, Joseph V.; Kyriakis, John M.

    2013-01-01

    Chronic stresses, including the mechanical strain caused by hypertension or excess pulmonary ventilation pressure, lead to important clinical consequences, including hypertrophy and acute respiratory distress syndrome. Pathologic hypertrophy contributes to decreased organ function and, ultimately, organ failure; and cardiac and diabetic renal hypertrophy are major causes of morbidity and morality in the developed world. Likewise, acute respiratory distress syndrome is a serious potential side effect of mechanical pulmonary ventilation. Whereas the deleterious effects of chronic stress are well established, the molecular mechanisms by which these stresses affect cell function are still poorly characterized. gene 33 (also called mitogen-inducible gene-6, mig-6) is an immediate early gene that is transcriptionally induced by a divergent array of extra-cellular stimuli. The physiologic function of Gene 33 is unknown. Here we show that gene 33 mRNA levels increase sharply in response to a set of commonly occurring chronic stress stimuli: mechanical strain, vasoactive peptides, and diabetic nephropathy. Induction of gene 33 requires the stress-activated protein kinases (SAPKs)/c-Jun NH2-terminal kinases. This expression pattern suggests that gene 33 is a potential marker for diabetic nephropathy and other pathologic responses to persistent sublethal stress. The structure of Gene 33 indicates an adapter protein capable of binding monomeric GTPases of the Rho subfamily. Consistent with this, Gene 33 interacts in vivo and, in a GTP-dependent manner, in vitro with Cdc42Hs; and transient expression of Gene 33 results in the selective activation of the SAPKs. These results imply a reciprocal, positive feedback relationship between Gene 33 expression and SAPK activation. Expression of Gene 33 at sufficient levels may enable a compensatory reprogramming of cellular function in response to chronic stress, which may have pathophysiological consequences. PMID:10749885

  3. Cross-species analyses identify the BNIP-2 and Cdc42GAP homology (BCH domain as a distinct functional subclass of the CRAL_TRIO/Sec14 superfamily.

    Directory of Open Access Journals (Sweden)

    Anjali Bansal Gupta

    Full Text Available The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP and Rho guanine nucleotide exchange factors (RhoGEFs. Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ~100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/Kh(R/K(R/KNL(R/KxhhhhHPs ('h' is large and hydrophobic residue and 's' is small and weekly polar residue and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding 'BCH-only' domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, 'BCH

  4. 骨髓间充质干细胞移植对慢性脑缺血大鼠海马区Cdc42表达及认知功能的影响%Transplantation of bone marrow mesenchymal stem cells increasing Cdc42 protein expression in the hippocampus and improving cognitive function of rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    于晓云; 张博爱; 李俊敏; 刘宇; 李晓晓; 崔璨; 崔红卫

    2013-01-01

    Objective To explore the effects of bone marrow mesenchymal stem cells transplantation on cognitive function and expression of cell division cycle 42 GTP-binding protein in hippocampus of chronic cerebral hypoperfusion rats. Methods 72 SD rats were randomly divided into sham, 2VO model (permanent ligation of bilateral common carotid artery) and experimental groups (2VO model + bone marrow mesenchymal stem cells transplantation). Rats in every group were subdivided into 8, 10 and 12 weeks subsets. Morris water maze was used to select rats of modeled successfully and space memory ability. Expression of Cdc42 protein in hippocampus was measured by Western blotting and immunohistochemistry. Results Expression of Cdc42 in hippocampus was reduced, escape latency was extended with time extending in experimental and model groups (P < 0. 05). Compared with model group, the expression of Cdc42 in the hippocampus tissue was increased and escape latency was shortened ( P < 0. 05 ) in experimental group. Conclusions Transplantation of bone marrow mesenchymal stem cells can improve cognitive function of chronic cerebral hypoperfusion rats, which maybe due to increased expression of Cdc42 protein.%目的 观察骨髓间充质干细胞移植后慢性脑缺血大鼠海马区表达Cdc42表达的变化,探讨其对慢性脑缺血大鼠认知功能的影响.方法 SD大鼠72只,随机分为假手术组、永久性双侧颈总动脉结扎(2VO)模型组、实验组(2VO模型+干细胞移植),每组分8、10、12w3个时间点,每个时间点8只,用Morris水迷宫筛选出造模成功的大鼠并检测大鼠的空间记忆能力,用Western印迹和免疫组化检测大鼠海马区Cdc42的表达.结果 实验组和模型组大鼠海马区Cdc42的表达随时间延长逐渐降低(P<0.05),其逃避潜伏期逐渐延长(P<0.05);较之2VO模型组,同一时间点实验组Cdc42表达明显增高(P<0.05),逃避潜伏期显著缩短(P<0.05).结论 骨髓间充质干细胞移植可显

  5. Cdc42 and the Actin-Related Protein/Neural Wiskott-Aldrich Syndrome Protein Network Mediate Cellular Invasion by Cryptosporidium parvum

    OpenAIRE

    Chen, Xian-Ming; Huang, Bing Q.; Splinter, Patrick L.; Orth, James D.; Billadeau, Daniel D.; McNiven, Mark A.; LaRusso, Nicholas F

    2004-01-01

    Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a remodeling of the host cell actin cytoskeleton. In addition, an actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interesting...

  6. The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

    OpenAIRE

    Anna Kirjavainen; Maarja Laos; Tommi Anttonen; Ulla Pirvola

    2015-01-01

    Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubul...

  7. Characterization of small GTPase Cdc42 from the ectomycorrhizal fungus Suillus bovinus and Agrobacterium tumefaciens-mediated transformation of fungi

    OpenAIRE

    Hanif, Mubashir

    2004-01-01

    Ectomycorrhizal formation between the host tree, Pinus sylvestris and fungal symbiont, Suillus bovinus was investigated at the molecular level by isolating genes regulating the organization of the actin cytoskeleton in the fungal partner S. bovinus. An Agrobacterium tumefaciens mediated transformation (ATMT) system was developed for the ectomycorrhizal fungi in order to assign specific functions to the cloned molecules. The developed ATMT system was also used to transform a plant pathogenic f...

  8. Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. A potential marker transcript for chronic pathologic conditions, such as diabetic nephropathy. Possible role in the response to persistent stress.

    Science.gov (United States)

    Makkinje, A; Quinn, D A; Chen, A; Cadilla, C L; Force, T; Bonventre, J V; Kyriakis, J M

    2000-06-01

    Chronic stresses, including the mechanical strain caused by hypertension or excess pulmonary ventilation pressure, lead to important clinical consequences, including hypertrophy and acute respiratory distress syndrome. Pathologic hypertrophy contributes to decreased organ function and, ultimately, organ failure; and cardiac and diabetic renal hypertrophy are major causes of morbidity and morality in the developed world. Likewise, acute respiratory distress syndrome is a serious potential side effect of mechanical pulmonary ventilation. Whereas the deleterious effects of chronic stress are well established, the molecular mechanisms by which these stresses affect cell function are still poorly characterized. gene 33 (also called mitogen-inducible gene-6, mig-6) is an immediate early gene that is transcriptionally induced by a divergent array of extracellular stimuli. The physiologic function of Gene 33 is unknown. Here we show that gene 33 mRNA levels increase sharply in response to a set of commonly occurring chronic stress stimuli: mechanical strain, vasoactive peptides, and diabetic nephropathy. Induction of gene 33 requires the stress-activated protein kinases (SAPKs)/c-Jun NH(2)-terminal kinases. This expression pattern suggests that gene 33 is a potential marker for diabetic nephropathy and other pathologic responses to persistent sublethal stress. The structure of Gene 33 indicates an adapter protein capable of binding monomeric GTPases of the Rho subfamily. Consistent with this, Gene 33 interacts in vivo and, in a GTP-dependent manner, in vitro with Cdc42Hs; and transient expression of Gene 33 results in the selective activation of the SAPKs. These results imply a reciprocal, positive feedback relationship between Gene 33 expression and SAPK activation. Expression of Gene 33 at sufficient levels may enable a compensatory reprogramming of cellular function in response to chronic stress, which may have pathophysiological consequences. PMID:10749885

  9. CD13/APN regulates endothelial invasion and filopodia formation

    OpenAIRE

    Petrovic, Nenad; Schacke, Wolfgang; Gahagan, J. Reed; O'Conor, Catherine A.; Winnicka, Beata; Conway, Rebecca E.; Mina-Osorio, Paola; Shapiro, Linda H.

    2007-01-01

    CD13/aminopeptidase N is a transmembrane peptidase that is induced in the vasculature of solid tumors and is a potent angiogenic regulator. Here, we demonstrate that CD13 controls endothelial cell invasion in response to the serum peptide bradykinin by facilitating signal transduction at the level of the plasma membrane. Inhibition of CD13 abrogates bradykinin B2 receptor internalization, leading to the attenuation of downstream events such as bradykinin-induced activation of Cdc42 and filopo...

  10. Collagen phagocytosis is regulated by the guanine nucleotide exchange factor Vav2

    OpenAIRE

    Arora, P. D.; Marignani, P A; McCulloch, C. A.

    2008-01-01

    Collagen phagocytosis is a crucial α2β1-integrin-dependent process that mediates extracellular matrix remodeling by fibroblasts. We showed previously that after initial contact with collagen, activated Rac1 accelerates collagen phagocytosis but the Rac guanine nucleotide exchange factors (GEFs) that regulate Rac are not defined. We examined here the GEFs that regulate collagen phagocytosis in mouse fibroblasts. Collagen binding enhanced Rac1 activity (5–20 min) but not Cdc42 or RhoA activity....

  11. A novel role for RhoA GTPase in the regulation of airway smooth muscle contraction.

    Science.gov (United States)

    Zhang, Wenwu; Huang, Youliang; Wu, Yidi; Gunst, Susan J

    2015-02-01

    Recent studies have demonstrated a novel molecular mechanism for the regulation of airway smooth muscle (ASM) contraction by RhoA GTPase. In ASM tissues, both myosin light chain (MLC) phosphorylation and actin polymerization are required for active tension generation. RhoA inactivation dramatically suppresses agonist-induced tension development and completely inhibits agonist-induced actin polymerization, but only slightly reduces MLC phosphorylation. The inhibition of MLC phosphatase does not reverse the effects of RhoA inactivation on contraction or actin polymerization. Thus, RhoA regulates ASM contraction through its effects on actin polymerization rather than MLC phosphorylation. Contractile stimulation of ASM induces the recruitment and assembly of paxillin, vinculin, and focal adhesion kinase (FAK) into membrane adhesion complexes (adhesomes) that regulate actin polymerization by catalyzing the activation of cdc42 GTPase by the G-protein-coupled receptor kinase-interacting target (GIT) - p21-activated kinase (PAK) - PAK-interacting exchange factor (PIX) complex. Cdc42 is a necessary and specific activator of the actin filament nucleation activator, N-WASp. The recruitment and activation of paxillin, vinculin, and FAK is prevented by RhoA inactivation, thus preventing cdc42 and N-WASp activation. We conclude that RhoA regulates ASM contraction by catalyzing the assembly and activation of membrane adhesome signaling modules that regulate actin polymerization, and that the RhoA-mediated assembly of adhesome complexes is a fundamental step in the signal transduction process in response to a contractile agonist. PMID:25531582

  12. Genetic Interactions among Regulators of Septin Organization

    Science.gov (United States)

    Gladfelter, Amy S.; Zyla, Trevin R.; Lew, Daniel J.

    2004-01-01

    Septins form a cortical scaffold at the yeast mother-bud neck that restricts the diffusion of cortical proteins between the mother and bud and serves as a signaling center that is important for governing various cell functions. After cell cycle commitment in late G1, septins are assembled into a narrow ring at the future bud site, which spreads to form a mature septin hourglass immediately after bud emergence. Although several septin regulators have been identified, it is unclear how they cooperate to assemble the septin scaffold. We have examined septin localization in isogenic strains containing single or multiple mutations in eight septin organization genes (CDC42, RGA1, RGA2, BEM3, CLA4, GIN4, NAP1, and ELM1). Our results suggest that these regulators act largely in parallel to promote either the initial assembly of the septin ring (CDC42, RGA1, RGA2, BEM3, and CLA4) or the conversion of the ring to a stable hourglass structure at the neck (GIN4, NAP1, and ELM1). Aberrant septin localization patterns in mutant strains could be divided into apparently discrete categories, but individual strains displayed heterogeneous defects, and there was no clear-cut correspondence between the specific mutations and specific categories of defect. These findings suggest that when they are deprived of their normal regulators, septin scaffolds collapse into a limited repertoire of aberrant states in which the nature of the mutant regulators influences the probability of a given aberrant state. PMID:15302817

  13. Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis.

    Science.gov (United States)

    Leung, Roland; Wang, Yongqiang; Cuddy, Karl; Sun, Chunxiang; Magalhaes, Joyce; Grynpas, Marc; Glogauer, Michael

    2010-05-01

    Osteoclastogenesis (OCG) results from the fusion of monocytes after stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). Migration of monocytes into close proximity precedes critical fusion events that are required for osteoclast formation. Cellular migration requires leading-edge actin cytoskeleton assembly that drives cellular locomotion. Filamin A (FLNa) cross-links F-actin filaments in the leading edge of migrating cells and also has been shown to regulate signal transduction during cell migration. However, little is known about the possible role of FLNa in osteoclastogenesis. Our objective in this study was to investigate the role of FLNa in osteoclastogenesis. Bone marrow monocytes isolated from the tibiae and femora of wild type (WT) and Flna-null mice were cultured for 6 days with M-CSF and RANKL, and osteoclasts were identified by tartrate-resistant acid phosphatase (TRACP) staining. The Flna-null mouse skeletal phenotype was characterized using dual-energy X-ray absorptiometry (DXA) to analyze the skeleton, as well as tests on blood chemistry. Osteoclast levels in vivo were quantified by counting of TRACP-stained histologic sections of distal femora. To elucidate the mechanisms by which Flna regulates osteoclastogenesis, migration, actin polymerization, and activation of Rho GTPases, Rac1, Cdc42, and RhoA were assessed in monocytes during in vitro OCG. Deficiencies in migration were rescued using constitutively active Rac1 and Cdc42 TAT fusion proteins. The RANKL signaling pathway was evaluated for activation by monitoring nuclear translocation of NF kappaB and c-jun and expression of key osteoclast genes using quantitative real-time polymerase chain reaction (qRT-PCR). Our results show that Flna-null monocytes formed fewer osteoclasts in vitro, and those that were formed were smaller with fewer nuclei. Decreased OCG was reflected in vivo in TRACP-stained histologic bone sections. Flna

  14. RAS and RHO Families of GTPases Directly Regulate Distinct Phosphoinositide 3-Kinase Isoforms

    OpenAIRE

    Fritsch, Ralph; de Krijger, Inge; Fritsch, Kornelia; George, Roger; Reason, Beth; Kumar, Madhu S.; Diefenbacher, Markus; Stamp, Gordon; Downward, Julian

    2013-01-01

    Summary RAS proteins are important direct activators of p110α, p110γ, and p110δ type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD). Here, we investigate the regulation of the ubiquitous p110β isoform of PI3K, implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, and thrombocyte function. Unexpectedly, RAS is unable to interact with p110β, but instead RAC1 and CDC42 from the RHO subfamily of small GTPases bind an...

  15. Cytoskeletal Regulation by AUTS2 in Neuronal Migration and Neuritogenesis

    Directory of Open Access Journals (Sweden)

    Kei Hori

    2014-12-01

    Full Text Available Mutations in the Autism susceptibility candidate 2 gene (AUTS2, whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. Immunohistochemistry and fractionation studies show that AUTS2 localizes not only in nuclei, but also in the cytoplasm, including in the growth cones in the developing brain. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These findings suggest that cytoplasmic AUTS2 acts as a regulator of Rho family GTPases to contribute to brain development and give insight into the pathology of human psychiatric disorders with AUTS2 mutations.

  16. Grit, a GTPase-Activating Protein for the Rho Family, Regulates Neurite Extension through Association with the TrkA Receptor and N-Shc and CrkL/Crk Adapter Molecules

    OpenAIRE

    Nakamura, Takeshi; Komiya, Misako; Sone, Kiyoaki; Hirose, Eiji; Gotoh, Noriko; Morii, Hiroshi; Ohta, Yasutaka; Mori, Nozomu

    2002-01-01

    Neurotrophins are key regulators of the fate and shape of neuronal cells and act as guidance cues for growth cones by remodeling the actin cytoskeleton. Actin dynamics is controlled by Rho GTPases. We identified a novel Rho GTPase-activating protein (Grit) for Rho/Rac/Cdc42 small GTPases. Grit was abundant in neuronal cells and directly interacted with TrkA, a high-affinity receptor for nerve growth factor (NGF). Another pool of Grit was recruited to the activated receptor tyrosine kinase thr...

  17. Dynamic Opposition of Clustered Proteins Stabilizes Cortical Polarity in the C. elegans Zygote.

    Science.gov (United States)

    Sailer, Anne; Anneken, Alexander; Li, Younan; Lee, Sam; Munro, Edwin

    2015-10-12

    Dynamic maintenance of cell polarity is essential for development and physiology. Here we combine experiments and modeling to elucidate mechanisms that maintain cortical polarity in the C. elegans zygote. We show that polarity is dynamically stabilized by two coupled cross-inhibitory feedback loops: one involves the oligomeric scaffold PAR-3 and the kinase PAR-1, and the other involves CDC-42 and its putative GAP CHIN-1. PAR-3 and CDC-42 are both required locally to recruit PAR-6/PKC-3, which inhibits PAR-1 (shown previously) and inhibits local growth/accumulation of CHIN-1 clusters. Conversely, PAR-1 inhibits local accumulation of PAR-3 oligomers, while CHIN-1 inhibits CDC-42 (shown previously), such that either PAR-1 or CHIN-1 can prevent recruitment of PAR-6/PKC-3, but loss of both causes complete loss of polarity. Ultrasensitive dependence of CHIN-1 cluster growth on PAR-6/PKC-3 endows this core circuit with bistable dynamics, while transport of CHIN-1 clusters by cortical flow can stabilize the AP boundary against diffusive spread of PAR-6/PKC-3. PMID:26460948

  18. Pak4 Is Required during Epithelial Polarity Remodeling through Regulating AJ Stability and Bazooka Retention at the ZA

    Science.gov (United States)

    Walther, Rhian F.; Nunes de Almeida, Francisca; Vlassaks, Evi; Burden, Jemima J.; Pichaud, Franck

    2016-01-01

    Summary The ability of epithelial cells to assemble into sheets relies on their zonula adherens (ZA), a circumferential belt of adherens junction (AJ) material, which can be remodeled during development to shape organs. Here, we show that during ZA remodeling in a model neuroepithelial cell, the Cdc42 effector P21-activated kinase 4 (Pak4/Mbt) regulates AJ morphogenesis and stability through β-catenin (β-cat/Arm) phosphorylation. We find that β-catenin phosphorylation by Mbt, and associated AJ morphogenesis, is needed for the retention of the apical determinant Par3/Bazooka at the remodeling ZA. Importantly, this retention mechanism functions together with Par1-dependent lateral exclusion of Par3/Bazooka to regulate apical membrane differentiation. Our results reveal an important functional link between Pak4, AJ material morphogenesis, and polarity remodeling during organogenesis downstream of Par3. PMID:27052178

  19. Rho GTPases and regulation of cell migration and polarization in human corneal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hou

    Full Text Available PURPOSE: Epithelial cell migration is required for regeneration of tissues and can be defective in a number of ocular surface diseases. This study aimed to determine the expression pattern of Rho family small G-proteins in human corneal epithelial cells to test their requirement in directional cell migration. METHODS: Rho family small G-protein expression was assessed by reverse transcription-polymerase chain reaction. Dominant-inhibitory constructs encoding Rho proteins or Rho protein targeting small interfering RNA were transfected into human corneal epithelial large T antigen cells, and wound closure rate were evaluated by scratch wounding assay, and a complementary non-traumatic cell migration assay. Immunofluorescence staining was performed to study cell polarization and to assess Cdc42 downstream effector. RESULTS: Cdc42, Chp, Rac1, RhoA, TC10 and TCL were expressed in human corneal epithelial cells. Among them, Cdc42 and TCL were found to significantly affect cell migration in monolayer scratch assays. These results were confirmed through the use of validated siRNAs directed to Cdc42 and TCL. Scramble siRNA transfected cells had high percentage of polarized cells than Cdc42 or TCL siRNA transfected cells at the wound edge. We showed that the Cdc42-specific effector p21-activated kinase 4 localized predominantly to cell-cell junctions in cell monolayers, but failed to translocate to the leading edge in Cdc42 siRNA transfected cells after monolayer wounding. CONCLUSION: Rho proteins expressed in cultured human corneal epithelial cells, and Cdc42, TCL facilitate two-dimensional cell migration in-vitro. Although silencing of Cdc42 and TCL did not noticeably affect the appearance of cell adhesions at the leading edge, the slower migration of these cells indicates both GTP-binding proteins play important roles in promoting cell movement of human corneal epithelial cells.

  20. Tissue damage negatively regulates LPS-induced macrophage necroptosis.

    Science.gov (United States)

    Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

    2016-09-01

    Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules. PMID:26943325

  1. BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

    International Nuclear Information System (INIS)

    The reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+) the derivative 9+ encodes either the p40(ABL/BCR) fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96(ABL/BCR) fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. We investigated the effects of BCR and ABL/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL/BCR fusion proteins in comparison to their physiological counterpart BCR

  2. BCR and its mutants, the reciprocal t(9;22-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

    Directory of Open Access Journals (Sweden)

    Puccetti Elena

    2006-11-01

    Full Text Available Abstract Background The reciprocal (9;22 translocation fuses the bcr (breakpoint cluster region gene on chromosome 22 to the abl (Abelson-leukemia-virus gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+ the derivative 9+ encodes either the p40(ABL/BCR fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96(ABL/BCR fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. Methods We investigated the effects of BCR and ABL/BCRs i. on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii. on the actin cytoskeleton by direct immunofluorescence; and iii on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. Results Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Conclusion Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22 ABL/BCR fusion proteins in comparison to their physiological counterpart BCR.

  3. Paradoxical signaling regulates structural plasticity in dendritic spines.

    Science.gov (United States)

    Rangamani, Padmini; Levy, Michael G; Khan, Shahid; Oster, George

    2016-09-01

    Transient spine enlargement (3- to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics. PMID:27551076

  4. Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration

    Science.gov (United States)

    Jones, Matthew C.; Machida, Kazuya; Mayer, Bruce J.; Turner, Christopher E.

    2013-01-01

    The Rho family of GTPases plays an important role in coordinating dynamic changes in the cell migration machinery after integrin engagement with the extracellular matrix. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and negatively regulated by GTPase-activating proteins (GAPs). However, the mechanisms by which GEFs and GAPs are spatially and temporally regulated are poorly understood. Here the activity of the proto-oncogene Vav2, a GEF for Rac1, RhoA, and Cdc42, is shown to be regulated by a phosphorylation-dependent interaction with the ArfGAP PKL (GIT2). PKL is required for Vav2 activation downstream of integrin engagement and epidermal growth factor (EGF) stimulation. In turn, Vav2 regulates the subsequent redistribution of PKL and the Rac1 GEF β-PIX to focal adhesions after EGF stimulation, suggesting a feedforward signaling loop that coordinates PKL-dependent Vav2 activation and PKL localization. Of interest, Vav2 is required for the efficient localization of PKL and β-PIX to the leading edge of migrating cells, and knockdown of Vav2 results in a decrease in directional persistence and polarization in migrating cells, suggesting a coordination between PKL/Vav2 signaling and PKL/β-PIX signaling during cell migration. PMID:23615439

  5. Regulating Rac in the Nervous System: Molecular Function and Disease Implication of Rac GEFs and GAPs

    Directory of Open Access Journals (Sweden)

    Yanyang Bai

    2015-01-01

    Full Text Available Rho family GTPases, including RhoA, Rac1, and Cdc42 as the most studied members, are master regulators of actin cytoskeletal organization. Rho GTPases control various aspects of the nervous system and are associated with a number of neuropsychiatric and neurodegenerative diseases. The activity of Rho GTPases is controlled by two families of regulators, guanine nucleotide exchange factors (GEFs as the activators and GTPase-activating proteins (GAPs as the inhibitors. Through coordinated regulation by GEFs and GAPs, Rho GTPases act as converging signaling molecules that convey different upstream signals in the nervous system. So far, more than 70 members of either GEFs or GAPs of Rho GTPases have been identified in mammals, but only a small subset of them have well-known functions. Thus, characterization of important GEFs and GAPs in the nervous system is crucial for the understanding of spatiotemporal dynamics of Rho GTPase activity in different neuronal functions. In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system.

  6. Cdc42p and Fus2p act together late in yeast cell fusion

    OpenAIRE

    Ydenberg, Casey A.; Stein, Richard A; Rose, Mark D.

    2012-01-01

    Cell fusion is the key event of fertilization that gives rise to the diploid zygote and is a nearly universal aspect of eukaryotic biology. In the yeast Saccharomyces cerevisiae, several mutants have been identified that are defective for cell fusion, and yet the molecular mechanism of this process remains obscure. One obstacle has been that genetic screens have mainly focused on mating-specific factors, whereas the process likely involves housekeeping proteins as well. Here we implicate Cdc4...

  7. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

    DEFF Research Database (Denmark)

    Lammermann, Tim; Renkawitz, Jorg; Wu, Xunwei; Hirsch, Karin; Brakebusch, Cord; Sixt, Michael

    2009-01-01

    Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular...

  8. Rho-family GTPase Cdc42 controls migration of Langerhans cells in vivo

    DEFF Research Database (Denmark)

    Luckashenak, Nancy; Wähe, Anna; Breit, Katharina;

    2013-01-01

    Epidermal Langerhans cells (LCs) of the skin represent the prototype migratory dendritic cell (DC) subtype. In the skin, they take up Ag, migrate to the draining lymph nodes, and contribute to Ag transport and immunity. Different depletion models for LCs have revealed contrasting roles and contri...

  9. RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms.

    Science.gov (United States)

    Fritsch, Ralph; de Krijger, Inge; Fritsch, Kornelia; George, Roger; Reason, Beth; Kumar, Madhu S; Diefenbacher, Markus; Stamp, Gordon; Downward, Julian

    2013-05-23

    RAS proteins are important direct activators of p110α, p110γ, and p110δ type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD). Here, we investigate the regulation of the ubiquitous p110β isoform of PI3K, implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, and thrombocyte function. Unexpectedly, RAS is unable to interact with p110β, but instead RAC1 and CDC42 from the RHO subfamily of small GTPases bind and activate p110β via its RBD. In fibroblasts, GPCRs couple to PI3K through Dock180/Elmo1-mediated RAC activation and subsequent interaction with p110β. Cells from mice carrying mutations in the p110β RBD show reduced PI3K activity and defective chemotaxis, and these mice are resistant to experimental lung fibrosis. These findings revise our understanding of the regulation of type I PI3K by showing that both RAS and RHO family GTPases directly regulate distinct ubiquitous PI3K isoforms and that RAC activates p110β downstream of GPCRs. PMID:23706742

  10. Ornithine decarboxylase and extracellular polyamines regulate microvascular sprouting and actin cytoskeleton dynamics in endothelial cells

    International Nuclear Information System (INIS)

    The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by α-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC inhibition was associated with an abnormal morphology of the actin cytoskeleton during cell spreading and migration. Moreover, our data suggest that de-regulated actin cytoskeleton dynamics in DFMO treated endothelial cells may be related to constitutive activation of the small GTPase CDC42, i.e. a well-known regulator of cell motility and actin cytoskeleton remodeling. These insights into the potential role of polyamines in angiogenesis should stimulate further studies testing the combined anti-tumor effect of polyamine inhibition and established anti-angiogenic therapies in vivo.

  11. Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and Endothelial Cell-Pericyte Interactions

    Science.gov (United States)

    Davis, George E.; Stratman, Amber N.; Sacharidou, Anastasia

    Recent studies have revealed a critical role for both extracellular matrices and matrix metalloproteinases in the molecular control of vascular morphogenesis and stabilization in three-dimensional (3D) tissue environments. Key interactions involve endothelial cells (ECs) and pericytes, which coassemble to affect vessel formation, remodeling, and stabilization events during development and postnatal life. EC-pericyte interactions control extracellular matrix remodeling events including vascular basement membrane matrix assembly, a necessary step for endothelial tube maturation and stabilization. ECs form tube networks in 3D extracellular matrices in a manner dependent on integrins, membrane-type metalloproteinases, and the Rho GTPases, Cdc42 and Rac1. Recent work has defined an EC lumen signaling complex of proteins composed of these proteins that controls 3D matrix-specific signaling events required for these processes. The EC tube formation process results in the creation of a network of proteolytically generated vascular guidance tunnels. These tunnels are physical matrix spaces that regulate vascular tube remodeling and represent matrix conduits into which pericytes are recruited to allow dynamic cell-cell interactions with ECs. These dynamic EC-pericyte interactions induce vascular basement membrane matrix deposition, leading to vessel maturation and stabilization.

  12. Negative regulation of caspase 3-cleaved PAK2 activity by protein phosphatase 1

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The p21-activated kinase 2 (PAK2) is activated by binding of small G proteins, Cdc42 and Rac, or through proteolytic cleavage by caspases or caspase-like proteases. Activation by both small G protein and caspase requires autophosphorylation at Thr-402 of PAK2. Although activation of PAK2 has been investigated for nearly a decade, the mechanism of PAK2 downregulation is unclear. In this study, we have applied the kinetic theory of substrate reaction during modification of enzyme activity to study the regulation mechanism of PAK2 activity by the catalytic subunit of protein phosphatase 1 (PP1α). On the basis of the kinetic equation of the substrate reaction during the reversible phosphorylation of PAK2, all microscopic kinetic constants for the free enzyme and enzyme-substrate(s) complexes have been determined. The results indicate that (1) PP1α can act directly on phosphorylated Thr-402 in the activation loop of PAK2 and down-regulate its kinase activity; (2) binding of the exogenous protein/peptide substrates at the active site of PAK2 decreases both the rates of PAK2 autoactivation and inactivation. The present method provides a novel approach for studying reversible phosphorylation reactions. The advantage of this method is not only its usefulness in study of substrate effects on enzyme modification but also its convenience in study of modification reaction directly involved in regulation of enzyme activity. This initial study should provide a foundation for future structural and mechanistic work of protein kinases and phosphatases.

  13. Negative regulation of caspase 3-cleaved PAK2 activity by protein phosphatase 1

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The p21-activated kinase 2 (PAK2) is activated by binding of small G proteins, Cdc42 and Rac, or through proteolytic cleavage by caspases or caspase-like proteases. Activation by both small G protein and caspase requires autophosphorylation at Thr-402 of PAK2. Although activation of PAK2 has been investigated for nearly a decade, the mechanism of PAK2 downregulation is unclear. In this study, we have applied the kinetic theory of substrate reaction during modification of enzyme activity to study the regulation mechanism of PAK2 activity by the catalytic subunit of protein phosphatase 1 (PP1α). On the basis of the kinetic equation of the substrate reaction during the reversible phosphorylation of PAK2, all microscopic kinetic constants for the free enzyme and enzyme-substrate(s) complexes have been determined. The results indicate that (1) PP1α can act directly on phosphorylated Thr-402 in the acti-vation loop of PAK2 and down-regulate its kinase activity; (2) binding of the exogenous protein/peptide substrates at the active site of PAK2 decreases both the rates of PAK2 autoactivation and inactivation. The present method provides a novel approach for studying reversible phosphorylation reactions. The advantage of this method is not only its usefulness in study of substrate effects on enzyme modifica-tion but also its convenience in study of modification reaction directly involved in regulation of enzyme activity. This initial study should provide a foundation for future structural and mechanistic work of protein kinases and phosphatases.

  14. Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI.

    Directory of Open Access Journals (Sweden)

    Mikko O Laukkanen

    Full Text Available Extracellular superoxide dismutase (SOD3, which catalyzes the dismutation of superoxide anions to hydrogen peroxide at the cell membranes, regulates the cellular growth in a dose-dependent manner. This enzyme induces primary cell proliferation and immortalization at low expression levels whereas it activates cancer barrier signaling through the p53-p21 pathway at high expression levels, causing growth arrest, senescence, and apoptosis. Because previous reports suggested that the SOD3-induced reduction in the rates of cellular growth and migration also occurred in the absence of functional p53 signaling, in the current study we investigated the SOD3-induced growth-suppressive mechanisms in anaplastic thyroid cancer cells. Based on our data, the robust over-expression of SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3, and EPHA10 receptor tyrosine kinases with the consequent downstream activation of the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth and migration signal transduction, such as the lack of stimulation of the mitogen pathway, in the SOD3 over-expressing cells, which was confirmed by MEK1/2 and ERK1/2 Western blotting analysis. Interestingly, the mRNA expression analyses indicated that SOD3 regulated the expression of guanine nucleotide-exchange factors (RHO GEF16, RAL GEF RGL1, GTPase-activating proteins (ARFGAP ADAP2, RAS GAP RASAL1, RGS4, and a Rho guanine nucleotide-disassociation inhibitor (RHO GDI 2 in a dose dependent manner, thus controlling signaling through the small G protein GTPases. Therefore, our current data may suggest the occurrence of dose-dependent SOD3-driven control of the GTP loading of small G proteins indicating a novel growth regulatory mechanism of this enzyme.

  15. Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI.

    Science.gov (United States)

    Laukkanen, Mikko O; Cammarota, Francesca; Esposito, Tiziana; Salvatore, Marco; Castellone, Maria D

    2015-01-01

    Extracellular superoxide dismutase (SOD3), which catalyzes the dismutation of superoxide anions to hydrogen peroxide at the cell membranes, regulates the cellular growth in a dose-dependent manner. This enzyme induces primary cell proliferation and immortalization at low expression levels whereas it activates cancer barrier signaling through the p53-p21 pathway at high expression levels, causing growth arrest, senescence, and apoptosis. Because previous reports suggested that the SOD3-induced reduction in the rates of cellular growth and migration also occurred in the absence of functional p53 signaling, in the current study we investigated the SOD3-induced growth-suppressive mechanisms in anaplastic thyroid cancer cells. Based on our data, the robust over-expression of SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3, and EPHA10 receptor tyrosine kinases with the consequent downstream activation of the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth and migration signal transduction, such as the lack of stimulation of the mitogen pathway, in the SOD3 over-expressing cells, which was confirmed by MEK1/2 and ERK1/2 Western blotting analysis. Interestingly, the mRNA expression analyses indicated that SOD3 regulated the expression of guanine nucleotide-exchange factors (RHO GEF16, RAL GEF RGL1), GTPase-activating proteins (ARFGAP ADAP2, RAS GAP RASAL1, RGS4), and a Rho guanine nucleotide-disassociation inhibitor (RHO GDI 2) in a dose dependent manner, thus controlling signaling through the small G protein GTPases. Therefore, our current data may suggest the occurrence of dose-dependent SOD3-driven control of the GTP loading of small G proteins indicating a novel growth regulatory mechanism of this enzyme. PMID:25751262

  16. Cla4p, a Saccharomyces cerevisiae Cdc42p-activated kinase involved in cytokinesis, is activated at mitosis.

    OpenAIRE

    Benton, B K; Tinkelenberg, A; Gonzalez, I.; Cross, F R

    1997-01-01

    Yeasts have three functionally redundant G1 cyclins required for cell cycle progression through G1. Mutations in GIN4 and CLA4 were isolated in a screen for mutants that are inviable with deletions in the G1 cyclins CLN1 and CLN2. cln1 cln2 cla4 and cln1 cln2 gin4 cells arrest with a cytokinesis defect; this defect was efficiently rescued by CLN1 or CLN2 expression. GIN4 encodes a protein with strong homology to the Snflp serine/threonine kinase. Cla4p is homologous to mammalian p21-activated...

  17. Dominant-Negative Rho, Rac, and Cdc42 Facilitate the Invasion Process of Vibrio parahaemolyticus into Caco-2 Cells

    OpenAIRE

    Akeda, Yukihiro; Kodama, Toshio; Kashimoto, Takashige; Cantarelli, Vlademir; Horiguchi, Yasuhiko; Nagayama, Kenichi; Iida, Tetsuya; Honda, Takeshi

    2002-01-01

    To clarify the invasive process of Vibrio parahaemolyticus, an invasion assay was performed using cells expressing dominant negative small GTPases of the Rho family. This assay showed that the dominant negative host phenotype facilitates bacterial invasion, suggesting that the mechanism of V. parahaemolyticus invasion differs from that reported for other invasive bacteria.

  18. The ROP2-RIC7 pathway negatively regulates light-induced stomatal opening by inhibiting exocyst subunit Exo70B1 in Arabidopsis.

    Science.gov (United States)

    Hong, Daewoong; Jeon, Byeong Wook; Kim, Soo Young; Hwang, Jae-Ung; Lee, Youngsook

    2016-01-01

    Stomata are the tiny valves on the plant surface that mediate gas exchange between the plant and its environment. Stomatal opening needs to be tightly regulated to facilitate CO2 uptake and prevent excess water loss. Plant Rho-type (ROP) GTPase 2 (ROP2) is a molecular component of the system that negatively regulates light-induced stomatal opening. Previously, ROP-interactive Cdc42- and Rac-interactive binding motif-containing protein 7 (RIC7) was suggested to function downstream of ROP2. However, the underlying molecular mechanism remains unknown. To understand the mechanism by which RIC7 regulates light-induced stomatal opening, we analyzed the stomatal responses of ric7 mutant Arabidopsis plants and identified the target protein of RIC7 using a yeast two-hybrid screen. Light-induced stomatal opening was promoted by ric7 knockout, whereas it was inhibited by RIC7 overexpression, indicating that RIC7 negatively regulates stomatal opening in Arabidopsis. RIC7 interacted with exocyst subunit Exo70 family protein B1 (Exo70B1), a component of the vesicle trafficking machinery. RIC7 and Exo70B1 localized to the plasma membrane region under light or constitutively active ROP2 conditions. The knockout mutant of Exo70B1 and ric7/exo70b1 exhibited retarded light-induced stomatal opening. Our results suggest that ROP2 and RIC7 suppress excess stomatal opening by inhibiting Exo70B1, which most likely participates in the vesicle trafficking required for light-induced stomatal opening. PMID:26451971

  19. Dual 4- and 5-phosphatase activities regulate SopB-dependent phosphoinositide dynamics to promote bacterial entry.

    Science.gov (United States)

    Piscatelli, Heather L; Li, Menghan; Zhou, Daoguo

    2016-05-01

    Salmonella are able to invade non-phagocytic cells such as intestinal epithelial cells by modulating the host actin cytoskeleton to produce membrane ruffles. Two type III effector proteins SopB and SopE play key roles to this modulation. SopE is a known guanine nucleotide exchange factor (GEF) capable of activating Rac1 and CDC42. SopB is a phosphatidylinositol 4-phosphatase and 5-phosphatase promoting membrane ruffles and invasion of Salmonella through undefined mechanisms. Previous studies have demonstrated that the 4-phosphatase activity of SopB is required for PtdIns-3-phosphate (PtdIns(3)P) accumulation and SopB-mediated invasion. We show here that both the 4-phosphatase as well as the 5-phosphatase activities of SopB are essential in ruffle formation and subsequent invasion. We found that the 5-phosphatase activity of SopB is likely responsible for generating PtdIns-3,4-bisphosphate (PtdIns(3,4)P2 ) and subsequent recruitment of sorting nexin 9 (SNX9), an actin modulating protein. Intriguingly, the 4-phosphatase activity is responsible for the dephosphorylation of PtdIns(3,4)P2 into PtdIns(3)P. Alone, neither activity is sufficient for ruffling but when acting in conjunction with one another, the 4-phosphatase and 5-phosphatase activities led to SNX9-mediated ruffling and Salmonella invasion. This work reveals the unique ability of bacterial effector protein SopB to utilize both its 4- and 5-phosphatase activities to regulate phosphoinositide dynamics to promote bacterial entry. PMID:26537021

  20. Dynamin Binding Protein (Tuba) Deficiency Inhibits Ciliogenesis and Nephrogenesis in Vitro and in Vivo.

    Science.gov (United States)

    Baek, Jeong-In; Kwon, Sang-Ho; Zuo, Xiaofeng; Choi, Soo Young; Kim, Seok-Hyung; Lipschutz, Joshua H

    2016-04-15

    Dysfunction of renal primary cilia leads to polycystic kidney disease. We previously showed that the exocyst, a protein trafficking complex, is essential for ciliogenesis and regulated by multiple Rho and Rab family GTPases, such as Cdc42. Cdc42 deficiency resulted in a disruption of renal ciliogenesis and a polycystic kidney disease phenotype in zebrafish and mice. Here we investigate the role of Dynamin binding protein (also known as Tuba), a Cdc42-specific guanine nucleotide exchange factor, in ciliogenesis and nephrogenesis using Tuba knockdown Madin-Darby canine kidney cells and tuba knockdown in zebrafish. Tuba depletion resulted in an absence of cilia, with impaired apical polarization and inhibition of hepatocyte growth factor-induced tubulogenesis in Tuba knockdown Madin-Darby canine kidney cell cysts cultured in a collagen gel. In zebrafish, tuba was expressed in multiple ciliated organs, and, accordingly, tuba start and splice site morphants showed various ciliary mutant phenotypes in these organs. Co-injection of tuba and cdc42 morpholinos at low doses, which alone had no effect, resulted in genetic synergy and led to abnormal kidney development with highly disorganized pronephric duct cilia. Morpholinos targeting two other guanine nucleotide exchange factors not known to be in the Cdc42/ciliogenesis pathway and a scrambled control morpholino showed no phenotypic effect. Given the molecular nature of Cdc42 and Tuba, our data strongly suggest that tuba and cdc42 act in the same ciliogenesis pathway. Our study demonstrates that Tuba deficiency causes an abnormal renal ciliary and morphogenetic phenotype. Tuba most likely plays a critical role in ciliogenesis and nephrogenesis by regulating Cdc42 activity. PMID:26895965

  1. The small GTPase RhoH is an atypical regulator of haematopoietic cells

    Directory of Open Access Journals (Sweden)

    Kubatzky Katharina F

    2008-09-01

    Full Text Available Abstract Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best-characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions such as actin cytoskeleton reorganisation, adhesion, motility as well as cell proliferation, differentiation and gene transcription. Among the 20 members of that family, only Rac2 and RhoH show an expression restricted to the haematopoietic lineage. RhoH was first discovered in 1995 as a fusion transcript with the transcriptional repressor LAZ3/BCL6. It was therefore initially named translation three four (TTF but later on renamed RhoH due to its close relationship to the Ras/Rho family of GTPases. Since then, RhoH has been implicated in human cancer as the gene is subject to somatic hypermutation and by the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and acute myeloid leukaemia. Some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have been described. These include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling. Little is currently known about its signalling, regulation or interaction partners. Recent studies have shown that RhoH negatively influences the proliferation and homing of murine haematopoietic progenitor cells, presumably by acting as an antagonist for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non-adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also been

  2. Efficient expression of isotopically labeled peptides for high resolution NMR studies: Application to the Cdc42/Rac binding domains of virulent kinases in Candida albicans

    International Nuclear Information System (INIS)

    The production of bioactive peptides and small protein fragments is commonly achieved via solid-phase chemical synthesis. However, such techniques become unviable and prohibitively expensive when the peptides are large (e.g., >30 amino acids) or when isotope labeling is required for NMR studies. Expression and purification of large quantities of unfolded peptides in E. coli have also proved to be difficult even when the desired peptides are carried by fusion proteins such as GST. We have developed a peptide expression system that utilizes a novel fusion protein (SFC120) which is highly expressed and directs the peptides to inclusion bodies, thereby minimizing in-cell proteolysis whilst maintaining high yields of peptide expression. The expressed peptides can be liberated from the carrier protein by CNBr cleavage at engineered methionine sites or through proteolysis by specific proteases for peptides containing methionine residues. In the present systems, we use CNBr, due to the absence of methionine residues in the target peptides, although other cleavage sites can be easily inserted. We report the production of six unfolded protein fragments of different composition and lengths (19 to 48 residues) derived from the virulent effector kinases, Cla4 and Ste20 of Candida albicans. All six peptides were produced with high yields of purified material (30-40 mg/l in LB, 15-20 mg/l in M9 medium), pointing to the general applicability of this expression system for peptide production. The enrichment of these peptides with 15N, 15N/13C and even 15N/13C/2H isotopes is presented allowing speedy assignment of poorly-resolved resonances of flexible peptides

  3. Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis

    DEFF Research Database (Denmark)

    Chrétien, Aline; Dierick, Jean-François; Delaive, Edouard; Larsen, Martin Røssel; Dieu, Marc; Raes, Martine; Deroanne, Christophe F; Roepstorff, Peter; Toussaint, Olivier

    2008-01-01

    The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-be...

  4. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  5. Telomerase Regulation

    OpenAIRE

    Cifuentes-Rojas, Catherine; Dorothy E Shippen

    2011-01-01

    The intimate connection between telomerase regulation and human disease is now well established. The molecular basis for telomerase regulation is highly complex and entails multiple layers of control. While the major target of enzyme regulation is the catalytic subunit TERT, the RNA subunit of telomerase is also implicated in telomerase control. In addition, alterations in gene dosage and alternative isoforms of core telomerase components have been described. Finally, telomerase localization,...

  6. Radiation regulation

    International Nuclear Information System (INIS)

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  7. NOISE REGULATION

    OpenAIRE

    Cristina Voican; Constantin Stanescu

    2012-01-01

    Noise regulation includes statutes or guidelines relating to sound transmission established by national, state or provincial and municipal levels of government. After the watershed passage of the United States Noise Control Act of 1972, other local and state governments passed further regulations. Although the UK and Japan enacted national laws in 1960 and 1967 respectively, these laws were not at all comprehensive or fully enforceable as to address generally rising ambient noise, enforceable...

  8. Roles of Rho GTPases in Intracellular Transport and Cellular Transformation

    Directory of Open Access Journals (Sweden)

    Ji-Long Chen

    2013-03-01

    Full Text Available Rho family GTPases belong to the Ras GTPase superfamily and transduce intracellular signals known to regulate a variety of cellular processes, including cell polarity, morphogenesis, migration, apoptosis, vesicle trafficking, viral transport and cellular transformation. The three best-characterized Rho family members are Cdc42, RhoA and Rac1. Cdc42 regulates endocytosis, the transport between the endoplasmic reticulum and Golgi apparatus, post-Golgi transport and exocytosis. Cdc42 influences trafficking through interaction with Wiskott-Aldrich syndrome protein (N-WASP and the Arp2/3 complex, leading to changes in actin dynamics. Rac1 mediates endocytic and exocytic vesicle trafficking by interaction with its effectors, PI3kinase, synaptojanin 2, IQGAP1 and phospholipase D1. RhoA participates in the regulation of endocytosis through controlling its downstream target, Rho kinase. Interestingly, these GTPases play important roles at different stages of viral protein and genome transport in infected host cells. Importantly, dysregulation of Cdc42, Rac1 and RhoA leads to numerous disorders, including malignant transformation. In some cases, hyperactivation of Rho GTPases is required for cellular transformation. In this article, we review a number of findings related to Rho GTPase function in intracellular transport and cellular transformation.

  9. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  10. RegulatING chromatin regulators

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Nabbi, Arash; Riabowol, Karl

    2013-01-01

    The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on...... the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine...... stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes...

  11. Nuclear regulation

    International Nuclear Information System (INIS)

    Today, 112 nuclear power plants, 22 facilities that support these plants, 54 reactors used in research, and approximately 23,000 organizations hold licenses from either the Nuclear Regulator Commission or various states to use radioactive material; other facilities are operated by various government agencies. Eventually most of these facilities will be decommissioned, which involves removing the radioactive material and terminating the license. NRC needs to ensure that licensees appropriately decontaminate their facilities because, under current regulations, NRC cannot specifically require additional cleanup once it terminates a license. This paper presents a GAO report on NRC's decommissioning procedures. In two of eight cases GAO reviewed, NRC fully or partially released sites for unrestricted use where radioactive contamination was higher than its guidelines allowed; in the other cases, NRC's information was inadequate or incomplete. Further, NRC lacks information on the types and amounts of radioactive waste buried on-site. At five sites reviewed by GAO, groundwater has been found to be contaminated by radioactive waste

  12. Dkk-1 Inhibits Intestinal Epithelial Cell Migration by Attenuating Directional Polarization of Leading Edge Cells

    OpenAIRE

    Koch, Stefan; Capaldo, Christopher T.; Samarin, Stanislav; Nava, Porfirio; Neumaier, Irmgard; Skerra, Arne; Sacks, David B; Parkos, Charles A.; Nusrat, Asma

    2009-01-01

    Wnt signaling pathways regulate proliferation, motility, and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted Wnt antagonist that has been proposed to regulate tissue homeostasis in the intestine. In this report, we show that Dkk-1 is secreted by intestinal epithelial cells after wounding and that it inhibits cell migration by attenuating the directional orientation of migrating epithelial cells. Dkk-1 exposure induced mislocalized activation of Cdc42 in migrating c...

  13. Dinámica de la actina y tráfico de membranas asociado al complejo de Golgi: papel regulador de RhoA, Rac1 y Cdc42

    OpenAIRE

    Matas Guadix, Olga Belén

    2005-01-01

    [spa] El trabajo llevado a cabo en esta tesis contribuye a esclarecer la relación morfo-funcional entre la actina y el complejo de Golgi. Estudios previos del laboratorio ponen de manifiesto que la actina regula no sólo la posición y morfología del complejo de Golgi en la célula (di Campli et al., 1999; Valderrama et al., 1998) sino también el transporte de proteínas desde el CG al retículo endoplasmático (transporte retrógrado; Valderrama et al., 2001). Un trabajo más reciente de nuestro gru...

  14. Gene 33/Mig-6, a Transcriptionally Inducible Adapter Protein That Binds GTP-Cdc42 and Activates SAPK/JNK*: A POTENTIAL MARKER TRANSCRIPT FOR CHRONIC PATHOLOGIC CONDITIONS, SUCH AS DIABETIC NEPHROPATHY. POSSIBLE ROLE IN THE RESPONSE TO PERSISTENT STRESS*

    OpenAIRE

    Makkinje, Anthony; Quinn, Deborah A; Chen, Ang; Cadilla, Carmen L.; Force, Thomas; Bonventre, Joseph V.; Kyriakis, John M.

    2000-01-01

    Chronic stresses, including the mechanical strain caused by hypertension or excess pulmonary ventilation pressure, lead to important clinical consequences, including hypertrophy and acute respiratory distress syndrome. Pathologic hypertrophy contributes to decreased organ function and, ultimately, organ failure; and cardiac and diabetic renal hypertrophy are major causes of morbidity and morality in the developed world. Likewise, acute respiratory distress syndrome is a serious potential side...

  15. Evolution of modular conidiophore development in the aspergilli.

    Science.gov (United States)

    Harris, Steven D

    2012-12-01

    Conidiophores are reproductive structures that enable filamentous fungi to produce and disseminate large numbers of asexual spores. The diversity in conidiophore morphology is sufficiently large to serve as a basis for fungal systematics. Aspergillus and Penicillium species are members of the family Trichocomaceae that form conidiophores with characteristic architecture. Whereas the Penicillium conidiophore appears to be a modified branched hyphal structure, the Aspergillus conidiophore is seemingly more complex and includes additional cell types. Here, it is proposed that the "aspergillioid" conidiophore may have evolved from a "penicillioid" ancestor via changes in expression of key regulators of the cell cycle and the GTPase Cdc42. Because the transcriptional regulatory network that controls conidiophore development in Aspergillus is well characterized, further study of how this network links to regulators of the cell cycle and Cdc42 should provide fundamental insight into the evolution of developmental morphogenesis in fungi (i.e., fungal evo-devo). PMID:23230831

  16. Regulations and instructions

    International Nuclear Information System (INIS)

    Regulations and instructions for operating the RA reactor consist of the following chapters: general regulations with the fundamental RA reactor characteristics, operating regulations and instructions for the personnel on duty, regulations for accidental conditions, training program for the staff of the Laboratory for reactor operation

  17. Activation of Rac1 by the Guanine Nucleotide Exchange Factor Dck1 Is Required for Invasive Filamentous Growth in the Pathogen Candida albicans

    OpenAIRE

    Hope, Hannah; Bogliolo, Stéphanie; Arkowitz, Robert A; Bassilana, Martine

    2008-01-01

    Rho G proteins and their regulators are critical for cytoskeleton organization and cell morphology in all eukaryotes. In the opportunistic pathogen Candida albicans, the Rho G proteins Cdc42 and Rac1 are required for the switch from budding to filamentous growth in response to different stimuli. We show that Dck1, a protein with homology to the Ced-5, Dock180, myoblast city family of guanine nucleotide exchange factors, is necessary for filamentous growth in solid media, similar to Rac1. Our ...

  18. Ectopic Expression of an Activated RAC in Arabidopsis Disrupts Membrane CyclingD⃞V⃞

    OpenAIRE

    Bloch, Daria; Lavy, Meirav; Efrat, Yael; Efroni, Idan; Bracha-Drori, Keren; Abu-Abied, Mohamad; Sadot, Einat; Yalovsky, Shaul

    2005-01-01

    Rho GTPases regulate the actin cytoskeleton, exocytosis, endocytosis, and other signaling cascades. Rhos are subdivided into four subfamilies designated Rho, Racs, Cdc42, and a plant-specific group designated RACs/Rops. This research demonstrates that ectopic expression of a constitutive active Arabidopsis RAC, AtRAC10, disrupts actin cytoskeleton organization and membrane cycling. We created transgenic plants expressing either wild-type or constitutive active AtRAC10 fused to the green fluor...

  19. Regulating Rho GTPases and their regulators.

    Science.gov (United States)

    Hodge, Richard G; Ridley, Anne J

    2016-08-01

    Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases. PMID:27301673

  20. Molecular characterization of a novel RhoGAP, RRC-1 of the nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    The GTPase-activating proteins for Rho family GTPases (RhoGAP) transduce diverse intracellular signals by negatively regulating Rho family GTPase-mediated pathways. In this study, we have cloned and characterized a novel RhoGAP for Rac1 and Cdc42, termed RRC-1, from Caenorhabditis elegans. RRC-1 was highly homologous to mammalian p250GAP and promoted GTP hydrolysis of Rac1 and Cdc42 in cells. The rrc-1 mRNA was expressed in all life stages. Using an RRC-1::GFP fusion protein, we found that RRC-1 was localized to the coelomocytes, excretory cell, GLR cells, and uterine-seam cell in adult worms. These data contribute toward understanding the roles of Rho family GTPases in C. elegans

  1. CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling.

    Science.gov (United States)

    Lant, Benjamin; Yu, Bin; Goudreault, Marilyn; Holmyard, Doug; Knight, James D R; Xu, Peter; Zhao, Linda; Chin, Kelly; Wallace, Evan; Zhen, Mei; Gingras, Anne-Claude; Derry, W Brent

    2015-01-01

    The mechanisms governing apical membrane assembly during biological tube development are poorly understood. Here, we show that extension of the C. elegans excretory canal requires cerebral cavernous malformation 3 (CCM-3), independent of the CCM1 orthologue KRI-1. Loss of ccm-3 causes canal truncations and aggregations of canaliculular vesicles, which form ectopic lumen (cysts). We show that CCM-3 localizes to the apical membrane, and in cooperation with GCK-1 and STRIPAK, promotes CDC-42 signalling, Golgi stability and endocytic recycling. We propose that endocytic recycling is mediated through the CDC-42-binding kinase MRCK-1, which interacts physically with CCM-3-STRIPAK. We further show canal membrane integrity to be dependent on the exocyst complex and the actin cytoskeleton. This work reveals novel in vivo roles of CCM-3·STRIPAK in regulating tube extension and membrane integrity through small GTPase signalling and vesicle dynamics, which may help explain the severity of CCM3 mutations in patients. PMID:25743393

  2. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  3. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  4. Regulation of Genetic Tests

    Science.gov (United States)

    ... advertised. The Commission has the authority to regulate advertising that delivers health-related information to consumers to ensure that it is not false or misleading. Top of page FDA Regulation and ...

  5. Activists versus Captured Regulators

    OpenAIRE

    Daubanes, Julien; Rochet, Jean-Charles

    2013-01-01

    We analyze the consequences of activism in a regulated industry where the regulator has been captured by the industry. Unlike ordinary economic agents, activists are insensitive to monetary incentives. Moreover, they are less well informed than regulators and their actions generate dead-weight costs. Yet we find that activism may increase social welfare because it disciplines captured regulators and reduces the social cost of imperfect regulatory systems.

  6. Hepcidin: regulation of the master iron regulator

    OpenAIRE

    2015-01-01

    Iron, an essential nutrient, is required for many diverse biological processes. The absence of a defined pathway to excrete excess iron makes it essential for the body to regulate the amount of iron absorbed; a deficiency could lead to iron deficiency and an excess to iron overload and associated disorders such as anaemia and haemochromatosis respectively. This regulation is mediated by the iron-regulatory hormone hepcidin. Hepcidin binds to the only known iron export protein, ferroportin (FP...

  7. The p38/MK2/Hsp25 pathway is required for BMP-2-induced cell migration.

    Directory of Open Access Journals (Sweden)

    Cristina Gamell

    Full Text Available BACKGROUND: Bone morphogenetic proteins (BMPs have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. METHODOLOGY/PRINCIPAL FINDINGS: Activation of p38 MAPK has been shown to be relevant for a number of BMP-2's physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38α or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. CONCLUSIONS: These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

  8. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  9. Views of the regulators

    International Nuclear Information System (INIS)

    In dealing with a challenging problem in occupational exposure the nuclear regulator in South Africa concluded that the involvement of stake holders was critical. Valuable lessons were learnt in the process. These related to co-operation amongst regulators, the involvement of regulators in addressing occupational exposure problems, the training of workers by the regulator and the need for technical training of the workers. In general, it was also learnt that regulators should establish mechanisms to measure and continuously improve the satisfaction of their stake holders. (author)

  10. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The Nuclear Safety Regulations for Nuclear Installations and Nuclear Safety Codes for Nuclear Pressure Retaining Components were issued by the NNSA in 1995. The Atomic Act and Regulations on the Safety Regulation for Transportation of Radioactive Materials have been finished and submitted to the State Council in 1995. At the same time the NNSA organized a revised collection of regulations on nuclear safety in both Chinese and English, titled 'The Collection of Regulations on Nuclear Safety of the People's Republic of China'. To enhance the implementation of newly issued nuclear safety regulations, the NNSA conducted seven times of propagating activities in relation to the regulations for nuclear pressure retaining components and research reactors design and operating in 1995

  11. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  12. The development of regulations

    International Nuclear Information System (INIS)

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

  13. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The enactment of nuclear safety regulations in 1996 is mainly focused on the preparation of related regulations, and safety guides for nuclear materials control, the reprocessing installations of spent fuels, the treatment and disposal for radioactive waste. The NNSA also assists the departments concerned of the State Council for modification on the 'Atomic Energy Act' (draft) and the' Regulations on the Safety Supervision and Control of Radioactive Materials Transportation' (draft)

  14. Attention in emotion regulation

    OpenAIRE

    Gelow, Stefan

    2013-01-01

    The concept of emotion and how to regulate it is a central aspect of modern psychology. Within the process model of emotion regulation (Gross, 1998), one issue is how attentional deployment affects emotion regulation and how this can be measured. In task 1, pictures of positive or negative valence were showed in two conditions, either attend or decrease emotional reaction, while participants’ eye movements were followed with an eye tracker. Ratings of arousal and valence were significantly af...

  15. Accounting Regulation in Ukraine

    OpenAIRE

    Hora, Michal; Chyzevska, Ludmila

    2013-01-01

    The aim of the paper is to evaluate the regulation and organization of accounting in Ukraine under the changes in the national economic system development and impact of IFRS implementation. The system of legal regulation of accounting in Ukraine is presented by five levels, each comprised of a number of corresponding subjects of regulation and documents. Typical Chart of Accounts is evidence of the continental accounting model in Ukraine. The accounting standards provide freedom of choice as ...

  16. Emotional regulation and friendship

    OpenAIRE

    Zaccagnini, J.L.; Ruiz-Aranda, D.

    2013-01-01

    Previous literature has been shown that emotional regulation facilitates the establishment and maintenance of social relations (Dodge Garber, 1991; Saarni, 1999). The objective of the present study was to analyze the influence of emotional regulation (Gross y John, 2003) in positive friendship (Berscheid, 2003), specifically at the level of intimacy with friends. In addition, we examined the mediating role of positive emotions in the relationship between the emotional regulation and the leve...

  17. Benchmarking and regulation

    OpenAIRE

    Agrell, Per Joakim; Bogetoft, Peter

    2013-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publication...

  18. Better Regulation in Europe

    OpenAIRE

    Wiener, Jonathan B.

    2006-01-01

    "Better Regulation" is afoot in Europe. After several transatlantic conflicts over regulatory topics such as the precautionary principle, genetically modified foods, and climate change, Europe and America now appear to be converging on the analytic basis for regulation. In a process of hybridization, European institutions are borrowing "Better Regulation" reforms from both the US approach to regulatory review using benefit-cost analysis and from European member states' initiatives on administ...

  19. Emotion-regulation choice

    NARCIS (Netherlands)

    Sheppes, Gal; Scheibe, Susanne; Suri, Gaurav; Gross, James J.

    2011-01-01

    Despite centuries of speculation about how to manage negative emotions, little is actually known about which emotion-regulation strategies people choose to use when confronted with negative situations of varying intensity. On the basis of a new process conception of emotion regulation, we hypothesiz

  20. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    nchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The applica...

  1. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... literature. First, contrary to what is commonly argued, we claim that strong states in Asia promote civil regulation in what we call the “paradox of the weak state”. Second, we not only argue that civil regulation is mainly enforced by multinational enterprises willing to promote international social and...... environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

  2. Regulation of megakaryocytopoiesis.

    Science.gov (United States)

    Caen, J P; Han, Z C; Bellucci, S; Alemany, M

    1999-09-01

    After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use in a wide variety of clinical megakaryocytic and platelet disorders has been expected and clinical trials have been undertaken. To date, the reported encouraging pre-clinical studies indicate that, as with erythropoietin or G-CSF, minimal toxicity can be expected. A potential limiting side-effect of TPO could be the induction of thrombosis. Nevertheless, it is too early to know whether this cytokine will be of major therapeutic importance for patients with life-threatening thrombocytopenia, such as patients undergoing bone marrow transplantation or subjected to a high dose of chemotherapy. Several experimental and clinical studies are still needed to determine the efficacy of TPO in the prevention or the amelioration of bleeding, which is the ultimate goal for the appropriate use of cytokines with haemostatic benefit. Basic and clinical studies on regulators of megakaryocytopoiesis have rapidly progressed. Now, there is no doubt that some of these regulators are effective in correcting haematopoietic disorders of various aetiologies. Studies on negative regulators not only are important to understand the regulation of megakaryocytopoiesis in normal and pathological states but also have a potential clinical application. Some of these regulators have been shown to be effective in the treatment of essential thrombocythaemia and other myeloproliferative disorders. Platelet factor 4 (PF4) and some other chemokines are also capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs. However, detailed investigations are still required to determine the precise mechanism(s) of action of these regulators and to establish the optimal clinical protocols of negative regulators alone or in association with positive regulators for the treatment of various

  3. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F

    1966-01-01

    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  4. The power of regulation

    International Nuclear Information System (INIS)

    Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

  5. Sport Fishing Regulations

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The regulations for sport fishing on St. Vincent National Wildlife Refuge are outlined in this document. Fishing is only permitted from sunrise to sunset, and only...

  6. Legislation and regulation

    International Nuclear Information System (INIS)

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation

  7. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  8. Optimal Regulation of Auditing

    OpenAIRE

    Pagano, Marco; Immordino, Giovanni

    2007-01-01

    We study regulation of the auditing profession in a model where audit quality is unobservable and enforcing regulation is costly. The optimal audit standard falls short of the first-best audit quality, and is increasing in the riskiness of firms and in the amount of funding they seek. The model can encompass collusion between clients and auditors, arising from the joint provision of auditing and consulting services: deflecting collusion requires less ambitious standards. Finally, banning the ...

  9. Restructuring nuclear regulations.

    OpenAIRE

    Mossman, Kenneth L.

    2003-01-01

    Nuclear regulations are a subset of social regulations (laws to control activities that may negatively impact the environment, health, and safety) that concern control of ionizing radiation from radiation-producing equipment and from radioactive materials. The impressive safety record among nuclear technologies is due, in no small part, to the work of radiation safety professionals and to a protection system that has kept pace with the rapid technologic advancements in electric power generati...

  10. Rethinking financial regulation

    OpenAIRE

    Thomas M. Hoenig

    1996-01-01

    In recent years, revolutionary changes in financial markets, combined with incidents such as Barings and Daiwa, have revived concerns about the adequacy of financial regulation. Historically, financial regulatory policy has been driven by the view that to maintain the health of the financial system you must maintain the health of individual institutions.> In light of ongoing changes in financial markets, however, extending the traditional approach to financial market regulation may not work. ...

  11. Supermarkets and Planning Regulation

    OpenAIRE

    Griffith, Rachel; Harmgart, Heike

    2008-01-01

    We are interested in evaluating the impact of restrictive planning regulation on entry into the UK grocery retail industry. We estimate a model similar to Bresnahan and Reiss (1991) where we allow for multiple store formats. We find that more restrictive planning regulation reduces the number of large format supermarkets in equilibrium. However, the impact is overstated if variation in demographic characteristics across markets is not also controlled for. Our estimates suggest that restrictiv...

  12. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  13. Summary of the regulations

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency (IAEA) prescribes regulations for the international movement of all radioactive materials among member nations. The U.S. governmental agencies regulating the transportation of radioactive materals include the Department of Transportation (DOT), which is responsible for safety in packaging, shipping, carriage, stowage, storage, and handling of all radioactive materials; the Nuclear Regulatory Commission (NRC), which is responsible for (1) safety and safeguards in receipt, possession, use, transfer of by-product, source, and special nuclear materials and (2) safety in packaging of fissile and radioactive materials in quantities exceeding Type A limits, defined in the Code of Federal Regulations; the Energy Research and Development Administration, which is responsible for safety in all aspects of radioactive material transport by its license-exempt contractors; and the Postal Service, which is responsible for safety in shipment by mail. Current regulatory actions involving NRC that may influence the transportation of radioactive materials include the examination of the regulations, legal contests, and the adoption of new regulations. The NRC published a draft of an environmental impact statement on transportation in March 1976 and will conduct a rulemaking proceeding after the final version of the statement is published in the fall. Of the new regulations, the most recent innovations in the IAEA regulations and a quality assurance program of increased rigor are foremost. The two most prominent ideas of the reguations IAEA regulations are the assignment of radiotoxicity values to each radionuclide rather than to grups of radionuclides, providing for increased flexibility in package limits for most radionuclides, and the allowance of small releases from Type B packages under hypothetical accident conditions. The DOT and NRC are in the process of adopting these IAEA revisions

  14. Financial Regulation Going Forward

    OpenAIRE

    Franklin Allen; Elena Carletti

    2010-01-01

    The financial sector is heavily regulated in order to prevent financial crises. The recent crisis showed how ineffective this regulation and other types of government intervention were in achieving this aim. We argue that the crisis was primarily caused by housing price bubbles. These occurred because of too loose monetary policies and the easy availability of credit resulting from the build up of large foreign exchange reserves by Asian central banks. A number of regulatory reforms are sugge...

  15. On Globalisation of Regulation

    Directory of Open Access Journals (Sweden)

    Bob Wessels

    2009-04-01

    Full Text Available In this article the opinion that financial regulation should be dealt with on a national, and not on a global scale is criticised. The objections against global regulation are discussed and dismissed. The greater good of a solid global system is inconsistent with maintaining the full force of national social or economic policies. Bob Wessels submits that the best way forward is to look for (a combination of the best methods of regulation on the basis of geography, the nature of regulation itself (hard law, best practices, guidelines, the function of certain rules in relation to the goals or the expectations they aim to address and the character of these rules. A parallel is drawn with the way in which cross-border insolvencies are regulated, including solutions from practitioners in the global insolvency of Lehman Brothers Group of Companies. Given the essential role courts play the presence of new rules of the international insolvency should be supported by more robust rules for the cross-border judicial coordination of cross-border cases, such as a convention. The body of financial regulation should be guided by international accepted principles and guidelines and international regulation and national implementation should reflect a balance between what is necessary in the light of the past events, while still leaving room for fair national demands and policies. The allocation of clear responsibility and authority to regulating bodies should warrant an efficient and effective answer for what, at the core, is a global problem, related to international financial markets.

  16. Corruption, Institutions and Regulation

    OpenAIRE

    Breen, Michael; Gillanders, Robert

    2011-01-01

    We analyze the effects of corruption and institutional quality on the quality of business regulation. Our key findings indicate that corruption negatively affects the quality of regulation and that general institutional quality is insignificant once corruption is con- trolled for. These findings hold over a number of specifications which include additional exogenous historical and geographic controls. The findings imply that policy-makers should focus on curbing corruption to improve regulati...

  17. The regulator's viewpoint

    International Nuclear Information System (INIS)

    The speaker recalls the task of regulators in establishing criteria and standards and assessing and controlling their fulfillment, as well as the fact that there are many types of radiological regulators, depending on their targets, structures, level of independence, and others. She also stresses that regulators take the environment presently into account to protect people as far as ionising radiation is concerned, that is, environmental protection is provided by present regulations, although implicitly based on an anthropocentric focus. In this sense, there is a clear need to develop a framework for the protection of environment, on the basis of the evolution of the present system. There is a preference for a unique, coherent, timely, integrated and manageable radiological human and environment protection system, which has to be developed internationally. Such an enhanced environmental protection framework needs of clearly defined specific 'bricks' (principles/criteria/tools). Regulators will face important challenges in adapting to an integrated man/environment protection framework, and need to act nationally in the meantime to fulfill obligations, as well as actively encourage international initiatives. A proposal on a radiological environmental framework is laid down, and finally she states the overall regulators viewpoint on this process: 'The path towards pragmatism and credibility'. (author)

  18. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils

    Institute of Scientific and Technical Information of China (English)

    Nariman A B Balenga; Maria Waldhoer; Elma Aflaki; Julia Kargl; Wolfgang Platzer; Ralf Schr(o)der; Stefanie Bl(a)ttermann; Evi Kostenis; Andrew J Brown; Akos Heinemann

    2011-01-01

    The directional migration of neutrophils towards inflammatory mediators,such as chemokines and cannabinoids,occurs via the activation of seven transmembrane G protein coupled receptors (7TM/GPCRs) and is a highly organized process.A crucial role for controlling neutrophil migration has been ascribed to the cannabinoid CB2 receptor (CB2R),but additional modulatory sites distinct from CB2R have recently been suggested to impact CB2R-mediated effector functions in neutrophils.Here,we provide evidence that the recently de-orphanized 7TM/GPCR GPR55potently modulates CB2R-mediated responses.We show that GPR55 is expressed in human blood neutrophils and its activation augments the migratory response towards the CB2R agonist 2-arachidonoylglycerol (2-AG),while inhibiting neutrophil degranulation and reactive oxygen species (ROS) production.Using HEK293 and HL60 cell lines,along with primary neutrophils,we show that GPR55 and CB2R interfere with each other's signaling pathways at the level of small GTPases,such as Rac2 and Cdc42.This ultimately leads to cellular polarization and efficient migration as well as abrogation of degranulation and ROS formation in neutrophils.Therefore,GPR55 limits the tissueinjuring inflammatory responses mediated by CB2R,while it synergizes with CB2R in recruiting neutrophils to sites of inflammation.

  19. Regulating energy industries

    International Nuclear Information System (INIS)

    The concept of sector-based regulation takes on significant importance in the context of market liberalization. The overall aim is to conciliate, in the considered sector, fair competition with the achievement of public service missions. However, the nature of the authority in charge of this regulation is not prone to harmonized clauses, even in Europe. For electricity for example, the 96/92/CE directive of 19 December 1996 concerning common rules for the inner electricity market, does not state this and Germany, which has not designed any sector-based regulator, applies the general procedure of litigation settlement by the equivalent of the competition Council. In France, the law Nr 2000-108 of 10 February 2000 defines the CRE (Electricity Regulation Commission) is article 28 as including six members, three of which are appointed by Government and the three others respectively by each of the presidents of the parliamentary assemblies. Many other countries have made the same choice. However, the scope of the missions given to these specialized authorities varies considerably according to the country. At European level, what are the different models of organisation of sector-based regulation in the energy field? How are the new regulators organised in relation with the competition authorities? Will the new models converge on the medium term or on the long term? Must we anticipate the creation of European regulation authorities to rule the problems concerning several national markets? What can we learn from the recent electricity crisis in California? To try and answer these questions, Mr Michel Matheu presented a European comparative study and before the debate started, Mr Pierre Couveinhes suggested a reflection on the practical implications of the analyses carried out. (authors)

  20. Nuclear regulation in transition

    International Nuclear Information System (INIS)

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

  1. Radiation emitting devices regulations

    International Nuclear Information System (INIS)

    The Radiation Emitting Devices Regulations are the regulations referred to in the Radiation Emitting Devices Act and relate to the operation of devices. They include standards of design and construction, standards of functioning, warning symbol specifications in addition to information relating to the seizure and detention of machines failing to comply with the regulations. The radiation emitting devices consist of the following: television receivers, extra-oral dental x-ray equipment, microwave ovens, baggage inspection x-ray devices, demonstration--type gas discharge devices, photofluorographic x-ray equipment, laser scanners, demonstration lasers, low energy electron microscopes, high intensity mercury vapour discharge lamps, sunlamps, diagnostic x-ray equipment, ultrasound therapy devices, x-ray diffraction equipment, cabinet x-ray equipment and therapeutic x-ray equipment

  2. Probiotics and Appetite Regulation

    DEFF Research Database (Denmark)

    Bjerg, Anne Toksvig

    resistance and blood lipid profile among others. Probiotics which are health promoting bacteria can potentially be used to affect the GM and thereby change metabolic outcomes of the host. Animal studies have shown associations between intake of probiotics and appetite regulation, but currently no human...... intestine, in an animal study and in two human studies the effect of the probiotic bacteria Lactobacillus paracasei subsp. paracasei L. casei W8 (W8) on appetite regulation, blood lipids and blood fatty acids. In addition, it was investigated if W8 had an effect on the fecal microbiota of the human...... (GCG) gene encoding GLP-1 and GLP-2 and expression of the gene SCD1 encoding stearoyl-CoA desaturase-1 (SCD1); which is involved in the formation of triacylglycerol (TAG); was studied in piglets supplemented with W8 for two weeks. To study the acute effect of W8 on appetite regulation, glycemic...

  3. Staff rules and regulations

    CERN Multimedia

    HR Department

    2007-01-01

    The 11th edition of the Staff Rules and Regulations, dated 1 January 2007, adopted by the Council and the Finance Committee in December 2006, is currently being distributed to departmental secretariats. The Staff Rules and Regulations, together with a summary of the main modifications made, will be available, as from next week, on the Human Resources Department's intranet site: http://cern.ch/hr-web/internal/admin_services/rules/default.asp The main changes made to the Staff Rules and Regulations stem from the five-yearly review of employment conditions of members of the personnel. The changes notably relate to: the categories of members of the personnel (e.g. removal of the local staff category); the careers structure and the merit recognition system; the non-residence, installation and re-installation allowances; the definition of family, family allowances and family-related leave; recognition of partnerships; education fees. The administrative circulars, some of which are being revised following the ...

  4. ANTICIPATING AND REGULATING BIOSYSTEM

    Directory of Open Access Journals (Sweden)

    Ion Iorga Siman

    2010-06-01

    Full Text Available Regulating biosystems closely related to human beings are structures still difficult to understand.Numerous intimate processes taking place in these systems, even their actual constitution, are insufficiently decoded, and that they have populated the world long before man invented the first regulator, appears not to have contributed much to their knowledge. This work is intended to highlight what regulating biosystems are.There is no secret that somatic muscles perform control operations which no act of moving would be possible without. All actions are the result of dynamic controlled processes adjusted to strict control laws. By treating them very seriously may lead to knowledge of processes occurring in complex systems

  5. Environmentally regulated aerospace coatings

    Science.gov (United States)

    Morris, Virginia L.

    1995-01-01

    Aerospace coatings represent a complex technology which must meet stringent performance requirements in the protection of aerospace vehicles. Topcoats and primers are used, primarily, to protect the structural elements of the air vehicle from exposure to and subsequent degradation by environmental elements. There are also many coatings which perform special functions, i.e., chafing resistance, rain erosion resistance, radiation and electric effects, fuel tank coatings, maskants, wire and fastener coatings. The scheduled promulgation of federal environmental regulations for aerospace manufacture and rework materials and processes will regulate the emissions of photochemically reactive precursors to smog and air toxics. Aerospace organizations will be required to identify, qualify and implement less polluting materials. The elimination of ozone depleting chemicals (ODC's) and implementation of pollution prevention requirements are added constraints which must be addressed concurrently. The broad categories of operations affected are the manufacture, operation, maintenance, and repair of military, commercial, general aviation, and space vehicles. The federal aerospace regulations were developed around the precept that technology had to be available to support the reduction of organic and air toxic emissions, i.e., the regulations cannot be technology forcing. In many cases, the regulations which are currently in effect in the South Coast Air Quality Management District (SCAQMD), located in Southern California, were used as the baseline for the federal regulations. This paper addresses strategies used by Southern California aerospace organizations to cope with these regulatory impacts on aerospace productions programs. All of these regulatory changes are scheduled for implementation in 1993 and 1994, with varying compliance dates established.

  6. Regulation as Rhetoric

    DEFF Research Database (Denmark)

    Boll, Karen; Györy, Csaba

    This paper analyses the way regulatory agencies strategically use public ‘rhetoric’ and ‘management of appearance’ to strengthen their regulation. It reports a comparative study of the Securities and Exchange Commission (SEC) which is the US federal securities regulator and the Danish Tax and...... environment, these two agencies apply strategies that appear to be strikingly similar, and these similarities are worth investigating not despite, but exactly because of the differing political and social environment. We track recent shifts in organizational practice at these two agencies and argue that both...

  7. Nuclear regulation and safety

    International Nuclear Information System (INIS)

    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed

  8. Nuclear regulations and environment

    International Nuclear Information System (INIS)

    After an historical overview of the nuclear regulation system in Argentina a description is made of the country's Nuclear Regulatory Authority (ARN) and of its regulation and control functions. Its organic structure is also outlined. A detailed report is given of the environmental monitoring activities in the sites of the operating Argentine nuclear power plants as well as those of the nuclear research centres. A special reference is made of the monitoring of the relevant uranium mining districts in Argentina. The radon determination in houses of several regions of the country is also mentioned

  9. Regulated underground storage tanks

    International Nuclear Information System (INIS)

    This guidance package is designed to assist DOE Field operations by providing thorough guidance on the underground storage tank (UST) regulations. [40 CFR 280]. The guidance uses tables, flowcharts, and checklists to provide a ''roadmap'' for DOE staff who are responsible for supervising UST operations. This package is tailored to address the issues facing DOE facilities. DOE staff should use this guidance as: An overview of the regulations for UST installation and operation; a comprehensive step-by-step guidance for the process of owning and operating an UST, from installation to closure; and a quick, ready-reference guide for any specific topic concerning UST ownership or operation

  10. Regulation, Competition, and Information

    OpenAIRE

    Mian Muhammad Javed

    2002-01-01

    You know it is very hard after the Governor, State Bank, to make a presentation but I will try to do it in a very mundane way. You know the Regulatory Bodies specially in the Economic Sector in recent times. There has been a sort of resurgence, leaving aside the regulation of the financial sector, which has been doing very well. Our old memory of regulation is not so pleasant. Long ago, there used to be a transport Authority which used to dole out “Route Permits” as political favours, and the...

  11. Cyberplagiarism in University Regulations

    Directory of Open Access Journals (Sweden)

    Santiago Cavanillas

    2008-12-01

    Full Text Available The article examines the legal framework for plagiarism, and its twofold nature of illicit appropriation (from the author of the plagiarized work and fraud (with regard to the target audience of the plagiarism. Based on these premises, academic cyberplagiarism is analysed as a form of plagiarism carried out using electronic tools in the university setting. The question of responsibility (who can regulate the legal consequences of plagiarism? before and after the Ley Orgánica de Universidades (organic law on universities, LOU is studied, as is the disciplinary handling of cyberplagiarism with the limited regulations currently in place at universities.

  12. The Impact of Regulating Social Science Research with Biomedical Regulations

    Science.gov (United States)

    Durosinmi, Brenda Braxton

    2011-01-01

    The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

  13. Nuclear safety regulations

    International Nuclear Information System (INIS)

    The Departmental Rules and The Safety Guides were issued by the NNSA in 1998. The NNSA performed the activities of propagation and implementation of nuclear safety regulations at QTNPP in order to improve the nuclear safety culture of operating organization and construct and contract organizations

  14. Emotion regulation during isolation

    Czech Academy of Sciences Publication Activity Database

    Poláčková Šolcová, Iva; Šolcová, Iva

    2012-01-01

    Roč. 47, Suppl. 1 (2012). ISSN 0020-7594. [International Congress of Psychology /30./. 22.07.2012-27.07.2012, Cape Town] R&D Projects: GA ČR(CZ) GAP407/11/2226 Institutional support: RVO:68081740 Keywords : emotion regulation * isolation * Mars500 Subject RIV: AN - Psychology

  15. International telecommunications market regulation

    OpenAIRE

    Productivity Commission

    2001-01-01

    On 23 February 1999 the Assistant Treasurer referred international telecommunic-ations market regulation for inquiry and report within six months. The report focused on the reform of international telecommunications markets, in particular on the payment arrangements between providers of international telecommunications services.

  16. Regulation after Bush

    OpenAIRE

    Hahn Robert; Passell Peter

    2008-01-01

    Barack Obama and John McCain have staked out very different positions on serious questions involving economic regulation everything from housing finance to alternative energy mandates but practical considerations will dissolve many of these differences, according to Robert Hahn and Peter Passell.

  17. Vehicle recycling regulations

    DEFF Research Database (Denmark)

    Smink, Carla

    2007-01-01

    The number of end-of-life vehicles (ELVs) in the EU is increasing continously. Around 75 percent of an ELV are recyclable metals. The forecast growth in the number of ELVs calls for regulation that aims to minimise the environmental impact of a car. Using Denmark as an example, this article...

  18. Jordan Corporate Governance Regulations

    OpenAIRE

    Jordan Institute of Directors

    2013-01-01

    As the importance of Corporate Governance increases, an awareness and understanding of the different relevant regulations becomes of paramount value. The importance and value of Corporate Governance is not the core of this publication. The publication is built around the premise that Corporate Governance is important and increasingly becoming of significant importance for growth, continued...

  19. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.

    2013-01-01

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  20. Legislation and regulation

    International Nuclear Information System (INIS)

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the legislative and regulatory framework, regulatory body and responsibility of the license holder

  1. Regulating the Internet

    Science.gov (United States)

    Anderson, Byron

    2007-01-01

    The Internet's breakthrough to primetime usage beginning in the mid-1990s evolved in an era of openness. Unfettered access seemed key to Internet development. An important foundation for the 1996 Telecommunications Act was the theory that the telecom industry would work best if it were free of government regulation, a guiding principle that has…

  2. Metabolic regulation of yeast

    Science.gov (United States)

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  3. Regulating emerging technologies

    International Nuclear Information System (INIS)

    Full text: The presentation is designed for individuals who are involved in therapeutic administration of radioactive material and the implementation of the radiation safety programme. The United States Nuclear Regulatory Commission (NRC) has regulatory authority over the medical use of by-product material and the radiation from by-product material. The presentation will address how the NRC regulates new medical uses (i.e. emerging technologies) used in radiation oncology that are too new to be covered in the current regulations. NRC's process that allows licensees to get approved for these emerging technologies until regulations are promulgated for the new modalities will be described. The presentation will also cover NRC's reporting requirements for medical events and other radiation safety-related incidents. Some examples of errors that have occurred for these new NRC-regulated activities will be provided. The root causes in these events will be identified to prevent similar additional incidents from occurring in other facilities performing the same type of therapy. (author)

  4. Regulation of Energy Balance.

    Science.gov (United States)

    Bray, George A.

    1985-01-01

    Explains relationships between energy intake and expenditure focusing on the cellular, chemical and neural mechanisms involved in regulation of energy balance. Information is referenced specifically to conditions of obesity. (Physicians may earn continuing education credit by completing an appended test). (ML)

  5. Regulating nuclear fuel waste

    International Nuclear Information System (INIS)

    When Parliament passed the Atomic Energy Control Act in 1946, it erected the framework for nuclear safety in Canada. Under the Act, the government created the Atomic Energy Control Board and gave it the authority to make and enforce regulations governing every aspect of nuclear power production and use in this country. The Act gives the Control Board the flexibility to amend its regulations to adapt to changes in technology, health and safety standards, co-operative agreements with provincial agencies and policy regarding trade in nuclear materials. This flexibility has allowed the Control Board to successfully regulate the nuclear industry for more than 40 years. Its mission statement 'to ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment' concisely states the Control Board's primary objective. The Atomic Energy Control Board regulates all aspects of nuclear energy in Canada to ensure there is no undue risk to health, safety, security or the environment. It does this through a multi-stage licensing process

  6. Lysosomal Trafficking Regulator (LYST).

    Science.gov (United States)

    Ji, Xiaojie; Chang, Bo; Naggert, Jürgen K; Nishina, Patsy M

    2016-01-01

    Regulation of vesicle trafficking to lysosomes and lysosome-related organelles (LROs) as well as regulation of the size of these organelles are critical to maintain their functions. Disruption of the lysosomal trafficking regulator (LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, prolonged bleeding, severe immunodeficiency, recurrent bacterial infection, neurologic dysfunction and hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes, cytolytic granules and platelet dense bodies. The most striking CHS ocular pathology observed is an enlargement of melanosomes in the retinal pigment epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and results in photophobia and decreased visual acuity. Understanding the molecular function of LYST and identification of its interacting partners may provide therapeutic targets for CHS and other diseases associated with the regulation of LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania amazonensis infections. PMID:26427484

  7. Yeast Interacting Proteins Database: YER118C, YER118C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YER118C SHO1 Transmembrane osmosensor, participates in activation of both the Cdc42p- and MAP ... ki ... participates in activation of both the Cdc42p- and MAP ... kinase-dependent filamentous growth pathway and th ... participates in activation of both the Cdc42p- and MAP ... kinase-dependent filamentous growth pathway and th ...

  8. Inconsistent Regulators: Evidence From Banking

    OpenAIRE

    Sumit Agarwal; David Lucca; Amit Seru; Francesco Trebbi

    2012-01-01

    US state chartered commercial banks are supervised alternately by state and federal regulators. Each regulator supervises a given bank for a fixed time period according to a predetermined rotation schedule. We use unique data to examine differences between federal and state regulators for these banks. Federal regulators are significantly less lenient, downgrading supervisory ratings about twice as frequently as state supervisors. Under federal regulators, banks report higher nonperforming loa...

  9. Regulating the private security industry

    CERN Document Server

    Percy, Sarah

    2002-01-01

    The under-regulation of the private security industry has increasingly become a topic of media and academic interest. This Adelphi Paper enters the debate by explaining why the industry requires further regulation, and what is wrong with the current system. It begins by briefly defining the industry and explaining the need for more effective regulation, before analysing three types of regulation: domestic, international and informal (including self-regulation).

  10. Leadership and the Independent Regulator

    OpenAIRE

    Jamison, Mark A.

    2005-01-01

    Being a utility regulator has perils because the independence of the regulator necessarily removes power from politicians, operators, and others. Furthermore, regulators are sometimes scapegoats for unpopular policies and unavoidably become involved in shaping the policies that they are supposed to implement. As a result of such frictions, regulators are sometimes removed from office or marginalized in some way. How can regulators not only survive in such an environment, but also thrive? Jami...

  11. Markets, religion, regulation

    DEFF Research Database (Denmark)

    Fischer, Johan

    2016-01-01

    of regulation, certification and standardization on a global scale. Building on research on global kosher (a Hebrew term meaning “fit” or “proper”), halal (an Arabic word that literally means “permissible” or “lawful”) and Hindu vegetarianism this paper argues that these economies or markets to a...... large extent are conditioned by and themselves condition forms of transnational governmentality, that is, new and often overlapping practices of government and grassroots politics. I explore religious economies and markets at three interrelated levels of the social scale: state and non-state regulation......Most recent scholarship on moral economies or religious markets argues for the compatibility of economies/markets and religious practices in particular national or regional contexts. However, over the last couple of decades or so religious markets have entered a new phase characterized by new forms...

  12. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  13. Volume Regulation in Epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    We review studies on regulatory volume decrease (RVD) and regulatory volume increase (RVI) of major ion and water transporting vertebrate epithelia. The rate of RVD and RVI is faster in cells of high osmotic permeability like amphibian gallbladder and mammalian proximal tubule as compared to...... amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... function of iso-osmotic fluid transport that depends on Na+ recirculation. The causative relationship is discussed for a fluid-absorbing and a fluid-secreting epithelium of which the Na+ recirculation mechanisms have been identified. A large number of transporters and ion channels involved in cell volume...

  14. Auditing and Regulations

    OpenAIRE

    Pettinicchio, A.K.

    2011-01-01

    Effective financial reporting has become of critical importance in our economic markets and the international accounting scandals of the last decades have accentuated the role of auditing in protecting stakeholders' interests and contributing to an efficient functioning of financial markets. Auditing regulation has been at the centre of recent international debates (e.g. EU Green paper; 2010) and different regulatory interventions have been put in place in different countries and in different...

  15. POTENT REGULATORS OF METABOLISM

    OpenAIRE

    Brun, Pierre-Jacques; Yang, Kryscilla Jian Zhang; Lee, Seung-Ah; Yuen, Jason J.; Blaner, William S.

    2012-01-01

    Retinoids (vitamin A and its analogs) are highly potent regulators of cell differentiation, cell proliferation, and apoptosis. Because of these activities, retinoids have been most extensively studied in the contexts of embryonic development and of proliferative diseases, especially cancer and skin disease. Recently, there has been considerable new research interest focused on gaining understanding of the roles that retinoids and/or retinoid-related proteins may have in the development of met...

  16. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

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

  17. Regulating hate speech online

    OpenAIRE

    Banks, James

    2010-01-01

    The exponential growth in the Internet as a means of communication has been emulated by an increase in far-right and extremist web sites and hate based activity in cyberspace. The anonymity and mobility afforded by the Internet has made harassment and expressions of hate effortless in a landscape that is abstract and beyond the realms of traditional law enforcement. This paper examines the complexities of regulating hate speech on the Internet through legal and technological frameworks. It ex...

  18. Iron regulation by hepcidin

    OpenAIRE

    Zhao, Ningning; Zhang, An-Sheng; Enns, Caroline A

    2013-01-01

    Hepcidin is a key hormone that is involved in the control of iron homeostasis in the body. Physiologically, hepcidin is controlled by iron stores, inflammation, hypoxia, and erythropoiesis. The regulation of hepcidin expression by iron is a complex process that requires the coordination of multiple proteins, including hemojuvelin, bone morphogenetic protein 6 (BMP6), hereditary hemochromatosis protein, transferrin receptor 2, matriptase-2, neogenin, BMP receptors, and transferrin. Misregulati...

  19. Gastrointestinal hormones regulating appetite

    OpenAIRE

    Chaudhri, Owais; Small, Caroline; Bloom, Steve

    2006-01-01

    The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably cons...

  20. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    2014-01-01

    This paper examines a tax/subsidy on hunters based on game population. The tax/subsidy is the difference between actual and optimal population multiplied by an individual, variable tax rate. The tax rate is, among other things, based on the difference between the marginal value of the game...... population to the hunter and the regulator and differences in user costs of the population. The paper shows that the population tax/subsidy secures a first-best optimum....

  1. Cyberplagiarism in University Regulations

    OpenAIRE

    Santiago Cavanillas

    2008-01-01

    The article examines the legal framework for plagiarism, and its twofold nature of illicit appropriation (from the author of the plagiarized work) and fraud (with regard to the target audience of the plagiarism). Based on these premises, academic cyberplagiarism is analysed as a form of plagiarism carried out using electronic tools in the university setting. The question of responsibility (who can regulate the legal consequences of plagiarism?) before and after the Ley Orgánica de Universidad...

  2. Fibronectin Mechanobiology Regulates Tumorigenesis

    OpenAIRE

    Wang, Karin; Seo, Bo Ri; Fischbach, Claudia; Gourdon, Delphine

    2015-01-01

    Fibronectin (Fn) is an essential extracellular matrix (ECM) glycoprotein involved in both physiological and pathological processes. The structure–function relationship of Fn has been and is still being studied, as changes in its molecular structure are integral in regulating (or dysregulating) its biological activities via its cell, matrix component, and growth factor binding sites. Fn comprises three types of repeating modules; among them, FnIII modules are mechanically unstable domains that...

  3. Beyond State Regulation

    OpenAIRE

    Madanat, Philip; Pies, Judith

    2011-01-01

    Holding the news media accountable has traditionally been a task of the state in Jordan. Media laws and regulations are numerous and do not leave too much space for self-regulatory practices on a national basis. The Jordan Press Association (JPA) is the core of so-called established media accountability institutions. It conducted a law-like code of ethics in 2003 and runs ombuds committees (currently three) dealing with mishaps of the media to prevent journalists from legal liability. Thou...

  4. Improving CS regulations.

    Energy Technology Data Exchange (ETDEWEB)

    Nesse, R.J.; Scheer, R.M.; Marasco, A.L.; Furey, R.

    1980-10-01

    President Carter issued Executive Order 12044 (3/28/78) that required all Federal agencies to distinguish between significant and insignificant regulations, and to determine whether a regulation will result in major impacts. This study gathered information on the impact of the order and the guidelines on the Office of Conservation and Solar Energy (CS) regulatory practices, investigated problems encountered by the CS staff when implementing the order and guidelines, and recommended solutions to resolve these problems. Major tasks accomplished and discussed are: (1) legislation, Executive Orders, and DOE Memoranda concerning Federal administrative procedures relevant to the development and analysis of regulations within CS reviewed; (2) relevant DOE Orders and Memoranda analyzed and key DOE and CS staff interviewed in order to accurately describe the current CS regulatory process; (3) DOE staff from the Office of the General Counsel, the Office of Policy and Evaluation, the Office of the Environment, and the Office of the Secretary interviewed to explore issues and problems encountered with current CS regulatory practices; (4) the regulatory processes at five other Federal agencies reviewed in order to see how other agencies have approached the regulatory process, dealt with specific regulatory problems, and responded to the Executive Order; and (5) based on the results of the preceding four tasks, recommendations for potential solutions to the CS regulatory problems developed. (MCW)

  5. Staff rules and regulations

    CERN Multimedia

    HR Department

    2007-01-01

    The 11th edition of the Staff Rules and Regulations, dated 1 January 2007, adopted by the Council and the Finance Committee in December 2006, is currently being distributed to departmental secretariats. The Staff Rules and Regulations, together with a summary of the main modifications made, will be available, as from next week, on the Human Resources Department's intranet site: http://cern.ch/hr-web/internal/admin_services/rules/default.asp The main changes made to the Staff Rules and Regulations stem from the five-yearly review of employment conditions of members of the personnel. The changes notably relate to: the categories of members of the personnel (e.g. removal of the local staff category); the careers structure and the merit recognition system; the non-residence, installation and re-installation allowances; the definition of family, family allowances and family-related leave; recognition of partnerships; education fees. The administrative circulars, some of which are being revised following the m...

  6. Taiwan Regulation of Biobanks.

    Science.gov (United States)

    Fan, Chien-Te; Hung, Tzu-Hsun; Yeh, Chan-Kun

    2015-01-01

    This paper introduces legal framework and governance structure in relation to the management and development of biobanks in Taiwan. At first, we briefly describe Taiwan's population, political system and health care system. Secondly, this research introduces biobanking framework of Taiwan including 25 biobanks established with the approval of the Ministry of Health and Welfare. In those biobanks, "Taiwan Biobank" is the first and the largest government-supported biobank which comprises population-based cohort study and disease- oriented study. Since the collection of information, data, and biological specimen of biobanks often involve highly sensitive personal information, in the legal framework of Taiwan, there is a specific regulation, "Human Biobank Management Act" (HBMA), which plays an important role in regulating biobanks in Taiwan. HBMA, the Personal Information Act and other regulations constitute a comprehensive legal and regulatory privacy framework of biobanks. Through the introduction and analysis of the current legal framework applicable to biobanks, we found that there are several challenges that need to be solved appropriately that involve duplicate review systems, the obstacles in the international collaboration, and data sharing between biobanks in Taiwan. PMID:26711420

  7. Whither tobacco product regulation?

    Science.gov (United States)

    McNeill, Ann; Hammond, David; Gartner, Coral

    2012-03-01

    Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets. PMID:22345253

  8. The international radioactive transportation regulations: A model for national regulations

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

  9. Multisite phosphorylation of the guanine nucleotide exchange factor Cdc24 during yeast cell polarization.

    Directory of Open Access Journals (Sweden)

    Stephanie C Wai

    Full Text Available BACKGROUND: Cell polarization is essential for processes such as cell migration and asymmetric cell division. A common regulator of cell polarization in most eukaryotic cells is the conserved Rho GTPase, Cdc42. In budding yeast, Cdc42 is activated by a single guanine nucleotide exchange factor, Cdc24. The mechanistic details of Cdc24 activation at the onset of yeast cell polarization are unclear. Previous studies have suggested an important role for phosphorylation of Cdc24, which may regulate activity or function of the protein, representing a key step in the symmetry breaking process. METHODOLOGY/PRINCIPAL FINDINGS: Here, we directly ask whether multisite phosphorylation of Cdc24 plays a role in its regulation. We identify through mass spectrometry analysis over thirty putative in vivo phosphorylation sites. We first focus on sites matching consensus sequences for cyclin-dependent and p21-activated kinases, two kinase families that have been previously shown to phosphorylate Cdc24. Through site-directed mutagenesis, yeast genetics, and light and fluorescence microscopy, we show that nonphosphorylatable mutations of these consensus sites do not lead to any detectable consequences on growth rate, morphology, kinetics of polarization, or localization of the mutant protein. We do, however, observe a change in the mobility shift of mutant Cdc24 proteins on SDS-PAGE, suggesting that we have indeed perturbed its phosphorylation. Finally, we show that mutation of all identified phosphorylation sites does not cause observable defects in growth rate or morphology. CONCLUSIONS/SIGNIFICANCE: We conclude that lack of phosphorylation on Cdc24 has no overt functional consequences in budding yeast. Yeast cell polarization may be more tightly regulated by inactivation of Cdc42 by GTPase activating proteins or by alternative methods of Cdc24 regulation, such as conformational changes or oligomerization.

  10. Nuclear regulation in 2000

    International Nuclear Information System (INIS)

    A key prerequisite to the development of a nuclear program to provide a country's electricity is that governments and the public are confident that a nuclear accident 'will not occur' over the whole life of the program. This can only be achieved by three elements being equally strong: an excellent design, a highly competent and safety conscious operator, and a strong competent regulator with appropriate legal powers. This paper will outline what is necessary to achieve the third of these prerequisites. It will outline the principles by which a Regulatory Agency ensures that licensees meet their responsibility for the safety of their nuclear plant, based on both internationally accepted ideas, the Nuclear Safety Convention, and Canadian practice. The paper will cover legislative principles -- what to include in legislation, what to include in regulations, and what to include in standards and guides. The problem of 'prescriptive requirements' versus 'general performance statements' in regulations will be addressed, and the implications of this problem on ensuring licensees retain responsibility for safety, and on licensees' desire for a high degree of certainty in what is expected of them, both to get a licence and to keep it, in today's economic climate. The paper will also address compliance and the differences between the lawyers' definition of compliance (meeting specific requirements defined by law) and the nuclear safety engineers' view of compliance, (meeting commitments made at the time a licence was given), and how these views can be reconciled. The paper will discuss how Canada's new Nuclear Safety and Control Act has addressed some of these issues, and how the Canadian Nuclear Safety Commission is implementing the new Act. The issue of transfer of regulatory programs and technology to the regulatory agencies of countries buying a nuclear plant from Canadian companies will be discussed, and examples given of how this has been accomplished to the benefit of

  11. Situated bio-regulation

    DEFF Research Database (Denmark)

    Prainsack, Barbara; Wahlberg, Ayo

    2013-01-01

    Several years ago, both authors engaged in research into bioscience and biomedical regulation in Asian countries. One of us (BP) explored why the regulatory and discursive embedding of human embryonic stem cell in Israel was much more permissive than elsewhere. The other author (AW) sought to und...... case studies meant bringing what we call ‘ethnographic sensibility’ to our research. This paper discusses the implications of this approach, which often entails rendering visible the contradictions and ‘disorders’ in what seems coherent and orderly....

  12. Regulering og simulering

    DEFF Research Database (Denmark)

    Steen-Thøde, Mogens

    Dette notat er primært udarbejdet til brug i undervisningen i kurset Energisystemer og Regulering pa civilingeniørlinien lndeklima og Energiøkonomi på Aalborg Universitet, hvilket naturligvis sætter sit spor bade i omfang og udvælgelse af emner. Hensigten er at give en introduktion til det teoret...... teoretiske grundlag for reguleringsteknikken samtidig med en indføring i simulering af dynamiske systemer, således at læseren får en rimelig forståelse af dynamiske systemers virkemåde og karakteristika....

  13. Ionising radiations regulations 1985

    International Nuclear Information System (INIS)

    The (UK) Ionising Radiations Regulations 1985 come into force on 1.1.86 with supporting Approved Code of Practice. They are discussed under the headings: introduction; notifications to start work with ionising radiations; dose limitation (ALARP -as low as reasonably practicable); designation of controlled and supervised areas; Radiation Protection Advisers to be appointed by employers; Local Rules; Radiation Protection Supervisors to be appointed by employers from among employees; instruction and training; dosimetry and medical surveillance; control of radioactive substances; radiation monitoring; assessment of hazards; articles and equipment. (U.K.)

  14. FACTORS REGULATING LIBERAL TRANSLATION

    Institute of Scientific and Technical Information of China (English)

    龚海红

    2012-01-01

    Literal translation and liberal translation are two important methods and both play key roles in translation.However,some textbooks say that most translations are literal translations while others maintain most are liberal ones,besides,some others suggest a combination of the two.This paper focuses on the facts that regulate liberal translation.Because of the differences in culture,society,history,geography,and so on,there exists a great difference between Chinese language and English language,which does naturally lead to the liberal translation.

  15. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    multiplied by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good...... of the individual harvest. However, information about the individual harvest may be costly to obtain. Thus, we may have to look for alternatives to the existing system. This paper proposes a population tax/subsidy as an alternative which is the difference between the actual and optimal population...

  16. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1992-01-01

    This report describes accomplishments over the past year on understanding of terpene synthesis in mint plants and sage. Specifically reported are the fractionation of 4-S-limonene synthetase, the enzyme responsible for the first committed step to monoterpene synthesis, along with isolation of the corresponding RNA and DNA cloning of its gene; the localization of the enzyme within the oil glands, regulation of transcription and translation of the synthetase, the pathway to camphor biosynthesis,a nd studies on the early stages and branch points of the isoprenoid pathway.

  17. Wiring regulations in brief

    CERN Document Server

    Tricker, Ray

    2012-01-01

    Tired of trawling through the Wiring Regs?Perplexed by Part P?Confused by cables, conductors and circuits?Then look no further! This handy guide provides an on-the-job reference source for Electricians, Designers, Service Engineers, Inspectors, Builders, Students, DIY enthusiastsTopic-based chapters link areas of working practice - such as cables, installations, testing and inspection, special locations - with the specifics of the Regulations themselves. This allows quick and easy identification of the official requirements relating to the situati

  18. REGULATION OF VASCULOGENESIS AND ANGIOGENESIS

    Science.gov (United States)

    Regulation of vasculogenesis and angiogenesis.B.D. AbbottReproductive Toxicology Division, Environmental Protection Agency, Research Triangle Park, North Carolina, USA Vasculogenesis and angiogenesis are regulated by a complex, interactive family of receptors and lig...

  19. Self-Regulation in School

    OpenAIRE

    Nett, Ulrike Elisabeth

    2010-01-01

    Successful self-regulation depends on the ability to regulate the self both motivationally and emotionally in order to protect the self and the learning process against competing personal needs as well as situational distractions. Successful self-regulation further requires students to adequately use metacognitive and cognitive learning strategies to organize the learning process efficiently. The studies presented in this dissertation focus on students' strategies for regulating themselves in...

  20. Mergers in Regulated Industries: Electricity

    OpenAIRE

    Dennis W. Carlton

    2007-01-01

    Mergers in any industry can raise complicated questions about the elimination of competition and the achievement of efficiencies. Mergers in regulated industries such as electricity raise even more complicated issues as the analyst needs to grapple with the constraining effects of regulation, multiple levels of regulation, the ability to evade regulation, and the desire for efficiency. This paper discusses the electricity industry in general and one particular electricity merger that the U.S....

  1. Strategic Behaviour under Regulation Benchmarking

    OpenAIRE

    Jamasb, Tooraj; Nillesen, Paul; Michael G. Pollitt

    2003-01-01

    Liberalisation of generation and supply activities in the electricity sectors is often followed by regulatory reform of distribution networks. In order to improve the efficiency of distribution utilities, some regulators have adopted incentive regulation schemes that rely on performance benchmarking. Although regulation benchmarking can influence the ?regulation game?, the subject has received limited attention. This paper discusses how strategic behaviour can result in inefficient behav...

  2. Nuclear regulation - the Canadian approach

    International Nuclear Information System (INIS)

    Although the Atomic Energy Control Board was established 35 years ago the basic philosophy of nuclear regulation in Canada and the underlying principles of the regulatory process remain essentially unchanged. This paper outlines the Canadian approach to nuclear regulation and explains in practical terms how the principles of regulation are applied. (author)

  3. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  4. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  5. Regulation as delegation

    Directory of Open Access Journals (Sweden)

    Oren Bar-Gill

    2016-03-01

    Full Text Available Objective to consider the conception of reverse delegation when the government acts a principal and an individual ndash an agent from the point of view of behavioral PrincipalAgent Theory. Methods statistical method sociological polling. Results In diverse areas ndash from retirement savings to consumer credit to prescription drug use to fuel economy and energy efficiency rules to tobacco consumption to food and beverage consumption ndash government makes decisions for us or endeavors to help us make better decisions thus serving as our agent. From the point of view of PrincipalAgent Theory and behavioral PrincipalAgent Theory a great deal of modern regulation can be helpfully evaluated as a hypothetical delegation. Shifting from personal decisions to public goods problems the authors view the idea of reverse delegation with the government as principal and the individuals as agents. They show that the essence of delegation changes depending on the context. The article describes conditions under which various approaches will make sense. Scientific novelty the paper is devoted to the foreign experience of regulation through delegation by the example of a country with developed market economy the USA. It shows the prospects of such approach in solving both the public and the private tasks. Application of PrincipalAgent Theory and behavioral PrincipalAgent Theory is viewed to distinguish between such types of hypothetical delegation as information default rules incentives precommitments mandates and prohibitions. The article considers the benefits and costs of delegation and circumstances in which one or another approach makes sense. Practical significance PrincipalAgent Theory is widely used in economics and political science and can serve as a convenient tool to consider the optimal scale and essence of the assistance rendered to us by the government as our agent. The paper is of interest for the Russian legal science as the institution of

  6. A pressure regulator

    International Nuclear Information System (INIS)

    A device for regulating the pressure of a gas in a glove box comprises a resiliently biassed pressure sensitive diaphragm and a spool valve operable by deflection of the diaphragm. The diaphragm is arranged to be exposed on one side to atmospheric pressure and on the other side to the pressure of the gas in the glove box, and the spool valve is used to control simultaneously the rates at which gas is pumped in and out of the glove box. The valve spool has two axially spaced circumferential grooves A, B which provide communication between conduits C, D and E, F respectively, the flow control along each path being effected by means of apertures in a sleeve within which the spool slides. (author)

  7. NCAM regulates cell motility

    DEFF Research Database (Denmark)

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna;

    2002-01-01

    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells...... independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a...... fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine...

  8. Views of the regulators

    International Nuclear Information System (INIS)

    It is important to remember what the concept and objective of optimization are and the role of dose constraints. In relation to exposures from any particular source within a practice, radiation protection shall be optimized so that the magnitude of individual doses, except for therapeutic medical exposures, the number of exposed people and the likelihood of incurring exposures will all be kept 'as low as reasonably achievable' (ALARA), economic and social factors being taken into account, within the restriction that the dose to individuals delivered by the source be subject to dose constraints. Dose constraints and dose limits to occupational exposures are necessary since the workers are not the direct beneficiaries of the exposures and the optimization procedures based on collective doses could result in inequities. The dose constraint has the secondary function of ensuring that the sum of the doses that an individual received from different practices to which the individual can be exposed does not exceed the dose limit. Before discussing co-operation, it is fundamental to provide a description of the role and responsibilities of the regulatory authority, employers and workers. The role and responsibilities of the regulatory authority in establishing regulations, granting authorizations, undertaking inspections, ensuring enforcement, and dealing with accidents and emergencies are set by the national legislation. To achieve this objective, the licensee is required to use, to the extent practicable, procedures and engineering controls that are based upon sound radiation protection and safety principles. The regulations establish that the licensees and employers of workers who are engaged in activities that involve or could involve occupational exposure shall be responsible for the protection of these workers against any occupational exposure that is not excluded from regulatory control

  9. TFEB regulates lysosomal proteostasis.

    Science.gov (United States)

    Song, Wensi; Wang, Fan; Savini, Marzia; Ake, Ashley; di Ronza, Alberto; Sardiello, Marco; Segatori, Laura

    2013-05-15

    Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a β-hexosaminidase mutant associated with the development of another LSD, Tay-Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs. PMID:23393155

  10. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  11. Regulation of the power sector

    CERN Document Server

    2013-01-01

    Regulation of the Power Sector is a unified, consistent and comprehensive treatment of the theories and practicalities of regulation in modern power-supply systems. The need for generation to occur at the time of use occasioned by the impracticality of large-scale electricity storage coupled with constant and often unpredictable changes in demand make electricity-supply systems large, dynamic and complex and their regulation a daunting task. Conceptually arranged in four parts, this book addresses both traditional regulatory frameworks and also liberalized and re-regulated environments. First, an introduction gives a full characterization of power supply including engineering, economic and regulatory viewpoints. The second part presents the fundamentals of regulation and the third looks at the regulation of particular components of the power sector in detail. Advanced topics and subjects still open or subject to dispute form the content of the fourth part. In a sector where regulatory design is the key driver...

  12. Nanomaterials: Regulation and Risk Assessment

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Grieger, Khara Deanne; Baun, Anders

    2013-01-01

    The topics of regulation and risk assessment of nanomaterials have never been more relevant and controversial in Europe than they are at this point in time. In this entry, we present and discuss a number of major pieces of legislation relevant for the regulation of nanomaterials, including REACH...... Foods Regulation. Chemical risk assessment provides a fundamental element in support of existing legislation. Risk assessment is normally said to consist of four elements, i.e., hazard identification, dose–response assessment, exposure assessment, and risk characterization. Each of these four elements......, the Water Framework Directive, pharmaceuticals regulation, and the Novel Foods Regulation. Current regulation of nanomaterials entail three overall challenges: 1) limitations in regard to terminology and definitions of key terms such as a “substance,” “novel food,” etc.; 2) safety assessment...

  13. Regulation of sphingomyelin metabolism.

    Science.gov (United States)

    Bienias, Kamil; Fiedorowicz, Anna; Sadowska, Anna; Prokopiuk, Sławomir; Car, Halina

    2016-06-01

    Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD). PMID:26940196

  14. Self-Regulated Reionization

    CERN Document Server

    Iliev, I T; Shapiro, P R; Pen, U L; Iliev, Ilian T.; Mellema, Garrelt; Shapiro, Paul R.; Pen, Ue-Li

    2006-01-01

    Recently, we have presented the first large-scale radiative transfer simulations of reionization. Here we present new simulations which extend the source halo mass range downward to 10^8M_solar, to capture the full range of halo masses thought to be primarily responsible for reionization by their star formation following atomic hydrogen radiative cooling and gravitational collapse. Haloes below about 10^9M_solar, however, are subject to Jeans-mass filtering in the ionized regions, which suppresses their baryonic content and their ability to release ionizing radiation. By including these smaller-mass haloes but accounting for their suppression, too, we find that reionization is ``self-regulating,'' as follows. As the mean ionized fraction rises, so does the fraction of the volume within which suppression occurs. Hence, the degree of suppression is related to the mean ionized fraction. Since low-mass haloes with high emissivity achieve a given mean ionized fraction earlier than do those with low efficiency, Jea...

  15. Between regulation and independence

    International Nuclear Information System (INIS)

    This article stresses, first, on the differences between electricity and gas in terms of storability and place of production before introducing the gas sector and its reorganization and re-structuration in the framework of energy markets deregulation. Then, it presents the actions carried out by the commission of energy regulation (CRE) intended to improve the operation of the gas market: improvement of transparency, incitation to invest in transportation infrastructures, organisation of the downstream market and development of regional gas markets. Since July 1, 2007, the opening of gas market is juridically and technically complete. The role of CRE is also to inform the consumers and to warrant a non-discriminatory access to infrastructures in a context of sound competition. On this point, the new situation is satisfactory but improvements are needed to increase the offer. The future objectives of CRE is to maintain a climate favorable to investments, to implement stable and efficient conditions of access to infrastructures and, finally, to regularly work at the European scale for the building up of a domestic gas market synonymous of security of supplies, sustainable development and competitiveness. (J.S.)

  16. Klonierung und funktionelle Analyse des Aktinreorganisators p150-Spir

    OpenAIRE

    Otto, Ines Maria

    2002-01-01

    Die c-Jun-N-terminale Kinase (JNK), ein Mitglied der Familie der MAP-Kinasen (Mi-togen Activated Protein Kinases), wirkt als signalübertragender Effektor, der den klei-nen GTPasen der Rho–Familie Rac und Cdc42 nachgeschaltet ist. Rho-GTPasen spielen eine Schlüsselrolle in der Regulation von zellulären Aktinstrukturen und steuern Prozesse in der Zelle, die Änderungen der Aktinstruktur erfordern, wie z.B. Änderungen der Zellmorphologie, Zellmigration, Wachstum und Differenzierung. Genetische St...

  17. DEF6, a Novel Substrate for the Tec Kinase ITK, Contains a Glutamine-rich Aggregation-prone Region and Forms Cytoplasmic Granules that Co-localize with P-bodies*

    OpenAIRE

    Hey, Fiona; Czyzewicz, Nathan; Jones, Peter; Sablitzky, Fred

    2012-01-01

    Localization of DEF6 (SLAT/IBP), a Rho-family guanine nucleotide exchange factor, to the center of the immune synapse is dependent upon ITK, a Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and Cdc42-dependent actin polymerization. Here we demonstrate that ITK both interacts with DEF6 and phosphorylates DEF6 at tyrosine residues Tyr210 and Tyr222. Expression of a GFP-tagged Y210E-Y222E phosphomimic resulted in the formation of DEF6 ...

  18. Differential Localization of Rho Gtpases in Live Cells

    OpenAIRE

    Michaelson, David; Silletti, Joseph; Murphy, Gretchen; D'Eustachio, Peter; Rush, Mark; Philips, Mark R.

    2001-01-01

    Determinants of membrane targeting of Rho proteins were investigated in live cells with green fluorescent fusion proteins expressed with or without Rho-guanine nucleotide dissociation inhibitor (GDI)α. The hypervariable region determined to which membrane compartment each protein was targeted. Targeting was regulated by binding to RhoGDIα in the case of RhoA, Rac1, Rac2, and Cdc42hs but not RhoB or TC10. Although RhoB localized to the plasma membrane (PM), Golgi, and motile peri-Golgi vesicle...

  19. Auditing and bank capital regulation

    OpenAIRE

    Edward Simpson Prescott

    2004-01-01

    Auditing is introduced into a model of bank capital regulation. Deterministic and stochastic auditing strategies are studied. Contrary to intuition, auditing of bank risk should be focused on the safest banks because they hold the least amount of capital. Risky banks, which hold more capital, need to be audited less. The importance of auditing by regulators and penalties for non-compliance are discussed in light of the Basel II capital regulation proposals. Emphasis is placed on the importanc...

  20. Regulations for RA reactor operation

    International Nuclear Information System (INIS)

    Regulations for RA reactor operation are written in accordance with the legal regulations defined by the Law about radiation protection and related legal acts, as well as technical standards according to the IAEA recommendations. The contents of this book include: fundamental data about the reactor; legal regulations for reactor operation; organizational scheme for reactor operation; general and detailed instructions for operation, behaviour in the reactor building, performing experiments; operating rules for operation under steady state and accidental conditions

  1. Regulations on Open Government Information

    Institute of Scientific and Technical Information of China (English)

    YOU XUEYUN

    2007-01-01

    @@ On April 24, 2007 the State Council promulgated Regulations of the People's Republic of China on Open Government Information (referred to as Regulations below), which will become effective on May 1, 2008. As the first administrative rule of the central government of China that aims to safeguard the public's right to know, the Regulations are of great significance in China's democratization and its establishment of the rule of law.

  2. Financial Private Regulation and Enforcement

    OpenAIRE

    Miller, Geoffrey

    2011-01-01

    This paper has been delivered within the context of the research project "Transnational Private Regulatory Regimes: Constitutional foundations and governance design". This paper considers the topic of private regulation and enforcement for internationally active financial services firms. The paper documents the following types of regulation and enforcement that involve significant private input: house rules, contracts, internal compliance, management-based regulation, private standard-sett...

  3. Strategic automation of emotion regulation

    OpenAIRE

    Schweiger-Gallo, Inge; Keil, Andreas; McCulloch, Kathleen C.; Rockstroh, Brigitte; Gollwitzer, Peter M.

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i...

  4. Uniform Practical Nonlinear Output Regulation

    OpenAIRE

    Marconi, Lorenzo; Praly, Laurent

    2008-01-01

    International audience In this paper, we present a solution to the problem of asymptotic and practical semiglobal regulation by output feedback for nonlinear systems. A key feature of the proposed approach is that practical regulation is achieved uniformly with respect to the dimension of the internal model and to the gain of the stabilizer near the zero error manifold. This property renders the approach interesting for a number of real cases by bridging the gap between output regulation t...

  5. Platelets actively sequester angiogenesis regulators

    OpenAIRE

    Lakka Klement, Giannoula; Yip, Tai-Tung; Cassiola, Flavia; Kikuchi, Lena; Cervi, David; Podust, Vladimir; Italiano, Joseph E.; Wheatley, Erin; Abou-Slaybi, Abdo; Bender, Elise; Almog, Nava; Kieran, Mark W.; Folkman, Judah

    2009-01-01

    Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor...

  6. The next restructuring: Environmental regulation

    International Nuclear Information System (INIS)

    From oil, to natural gas, and now electricity, the regulation of energy markets has been successively restructured to allow greater scope to market forces. The likely next domain for restructuring, environmental regulation, may seem far-fetched now, but it is no more so than the restructuring of electric utility regulation would have seemed to be twenty years ago. The grand experiment with emissions trading under the US acid rain program has set a propitious example by showing that markets in environmental goods can be constructed and that the explicit recognition of property rights in the use of the environment is compatible with effective and non-intrusive environmental regulation

  7. Utility regulation and competition policy

    International Nuclear Information System (INIS)

    Contents: 1. The New Electricity Trading Arrangements in England and Wales: A Review - David Currie, 2. A Critique of Rail Regulation - Dieter Helm, 3. Moving to a Competitive Market in Water - Colin Robinson, 4. The New Gas Trading Arrangements - George Yarrow, 5. A Review of Privatization and Regulation Experience in Britain - Irwin M. Stelzer, 6. Converging Communications: Implications for Regulation - Mark Armstrong, 7. Opening European Electricity and Gas Markets - Graham Shuttleworth, 8. Concurrency or Convergence? Competition and Regulation Under the Competition Act 1998 - Tom Sharpe QC, 9. Ten Years of European Merger Control - Paul Seabright. (Author)

  8. Power-MOSFET Voltage Regulator

    Science.gov (United States)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  9. A role for PP1/NIPP1 in steering migration of human cancer cells.

    Directory of Open Access Journals (Sweden)

    Cristina Martin-Granados

    Full Text Available Electrical gradients are present in many developing and regenerating tissues and around tumours. Mimicking endogenous electric fields in vitro has profound effects on the behaviour of many cell types. Intriguingly, specific cell types migrate cathodally, others anodally and some polarise with their long axis perpendicular to the electric vector. These striking phenomena are likely to have in vivo relevance since one of the determining factors during cancer metastasis is the ability to switch between attractive and repulsive migration in response to extracellular guidance stimuli. We present evidence that the cervical cancer cell line HeLa migrates cathodally in a direct current electric field of physiological intensity, while the strongly metastatic prostate cancer cell line PC-3-M migrates anodally. Notably, genetic disruption of protein serine/threonine phosphatase-1 (PP1 and its regulator NIPP1 decrease directional migration in these cell lines. Conversely, the inducible expression of NIPP1 switched the directional response of HeLa cells from cathodal to slightly anodal in a PP1-dependent manner. Remarkably, induction of a hyperactive PP1/NIPP1 holoenzyme, further shifted directional migration towards the anode. We show that PP1 association with NIPP1 upregulates signalling by the GTPase Cdc42 and demonstrate that pharmacological inhibition of Cdc42 in cells overexpressing NIPP1 recovered cathodal migration. Taken together, we provide the first evidence for regulation of directional cell migration by NIPP1. In addition, we identify PP1/NIPP1 as a novel molecular compass that controls directed cell migration via upregulation of Cdc42 signalling and suggest a way by which PP1/NIPP1 may contribute to the migratory properties of cancer cells.

  10. Regulation of electricity prices?

    International Nuclear Information System (INIS)

    In this paper author deals with the regulation of electricity prices in the Slovak Republic. Author contests the social policy of the government through doped prices of electricity. Two thirds of electricity is generated in nuclear power plants in Slovakia. Hence, it is necessary to focus on the solution of problem of nuclear waste. In 2004 Ministry of Economy stated, that the deficit in nuclear fund, from which the country have to fully cover the costs of liquidation and final disposal of nuclear waste, is estimated in the amount of around 89 billion Slovak crowns (≅ 3.7 billion $). From it, so called historical deficit, which originated because of late foundation of fund, represents officially 15 billion Slovak crowns (≅ 0.62 billion $). In Slovakia exists the real risk, that by maintenance of present state by creation and draw of the fund, it will be possible to ensure only 39 per cent of financial sources necessary for full financial handling of the back part of nuclear energetic. Even though the Ministry of Economy in connection with privatisation of Slovenske elektrarne designed to decrease the transfers of operators of nuclear power plants into nuclear fund. In 2006 the Parliament decreased by the law the level of gains of the fund from sale of nuclear electricity (the second from two components of the gains of the fund) from 6.8 to 5.95 per cent from annual revenues. So the tax of forced reduction of the price of nuclear electricity will be represented by loading of the further generations

  11. Views of the regulators

    International Nuclear Information System (INIS)

    The International Commission on Radiological Protection (ICRP) offers its recommendations to regulatory and advisory bodies and provides advice to help management and professional staff with responsibility for radiation protection. The ICRP has no formal power to impose its proposals. However, legislation and regulations in most countries adhere closely to ICRP recommendations. The recommendations of the ICRP are based upon the fundamental principles and quantitative bases upon which appropriate radiation protection measures can be established. The radiation protection system recommended by the ICRP in its Publication 60 is based upon: (a) Justification principle: A practice or an activity that involves ionizing radiation exposure is justified if the anticipated benefit is greater than the risk incurred. (b) Optimization principle: All exposures from justified practices shall be kept as low as reasonably achievable (ALARA), economic and social factors being taken into account. (c) Individual dose and risk limits: Individual doses resulting from all relevant practices shall be subject to dose limits and risk limits in cases where potential exposures are likely. To manage risks, three levels are usually distinguished: unacceptable risk, tolerable risk and acceptable risk. The aim of radiation protection is to reduce the radiation exposure level to below that designated as having unacceptable risk. When radiation protection is optimized, the residual risk level becomes acceptable. Any additional measure is ineffective both from economic and social points of view. Regulatory limits adopted from ICRP recommendations are set such that continued exposure at a dose just above the limit would be unacceptable on any reasonable ground. Continued exposure at a level just below the dose limit might be tolerated but would not be welcome. Acceptable doses are those that are below the limit. Individual doses are only acceptable if they are optimized

  12. Regulating Pornography: A Public Dilemma.

    Science.gov (United States)

    Thompson, Margaret E.; And Others

    1990-01-01

    Examines attitudes toward sex and pornography by means of a telephone survey of Dane County, Wisconsin, adults. Describes survey questions about sexual attitudes, perceived effects of pornography, and pornography regulation. Concludes that adults who feel more strongly that pornography has negative effects are more opposed to its regulation. (SG)

  13. The economics of bank regulation

    OpenAIRE

    Bhattacharya, Sudipto; Arnoud W.A. Boot; Anjan V. Thakor

    1995-01-01

    The object of this paper is to survey and synthesize the literature on the regulation of financial intermediaries, including the theoretical framework and also the applied literature on specific regulations such as deposit insurance, capital controls, line of business restrictions, etc.

  14. Environmental awareness, legislations and regulations

    International Nuclear Information System (INIS)

    This paper presents a brief review of environmental awareness, legislation and regulation policies adopted in Indian nuclear power programme. Brief account of environmental legislations in India, water act, air act, environmental protection act, regulations pertaining to accidents, constitutional procedures, regulatory frame work for the protection of the environment from ionizing radiation are also discussed. (author)

  15. Deceptive Business Practices: Federal Regulations.

    Science.gov (United States)

    Rohrer, Daniel Morgan

    Federal regulations to prevent deceptive advertising seek to balance the advertiser's freedom of speech with protection of the consumer. This paper discusses what the Federal Trade Commission (FTC) has done to regulate advertising and evaluates the adequacy of its controls. The commission uses cease-and-desist orders, affirmative disclosure,…

  16. Assessing self-regulation strategies

    DEFF Research Database (Denmark)

    de Vet, Emely; de Ridder, Denise T. D.; Stok, Marijn;

    2014-01-01

    Background: Applying self-regulation strategies have proven important in eating behaviors, but it remains subject to investigation what strategies adolescents report to use to ensure healthy eating, and adequate measures are lacking. Therefore, we developed and validated a self-regulation questio...

  17. Splicing regulators: targets and drugs

    OpenAIRE

    Yeo, Gene Wei-Ming

    2005-01-01

    Silencing of splicing regulators by RNA interference, combined with splicing-specific microarrays, has revealed a complex network of distinct alternative splicing events in Drosophila, while a high-throughput screen of more than 6,000 compounds has identified drugs that interfere specifically and directly with one class of splicing regulators in human cells.

  18. RNA-guided transcriptional regulation

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  19. Regulation of gas infrastructure expansion

    International Nuclear Information System (INIS)

    The topic of this dissertation is the regulation of gas infrastructure expansion in the European Union (EU). While the gas market has been liberalised, the gas infrastructure has largely remained in the regulated domain. However, not necessarily all gas infrastructure facilities - such as gas storage facilities, LNG import terminals and certain gas transmission pipelines - need to be regulated, as there may be scope for competition. In practice, the choice of regulation of gas infrastructure expansion varies among different types of gas infrastructure facilities and across EU Member States. Based on a review of economic literature and on a series of in-depth case studies, this study explains these differences in choices of regulation from differences in policy objectives, differences in local circumstances and differences in the intrinsic characteristics of the infrastructure projects. An important conclusion is that there is potential for a larger role for competition in gas infrastructure expansion.

  20. Strategic automation of emotion regulation.

    Science.gov (United States)

    Gallo, Inge Schweiger; Keil, Andreas; McCulloch, Kathleen C; Rockstroh, Brigitte; Gollwitzer, Peter M

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i.e., an if-then plan), and a no-self-regulation control group. Only implementation-intention participants succeeded in reducing their disgust and fear reactions as compared to goal-intention and control participants. In Study 3, electrocortical correlates (using dense-array electroencephalography) revealed differential early visual activity in response to spider slides in ignore implementation-intention participants, as reflected in a smaller P1. Theoretical and applied implications of the present findings for emotion regulation via implementation intentions are discussed. PMID:19210061

  1. Designing Next Generation Telecom Regulation

    DEFF Research Database (Denmark)

    Henten, Anders; Samarajiva, Rohan

    – ICT convergence regulation and multisector utility regulation. Whatever structure of next generation telecom regulation is adopted, all countries will need to pay much greater attention to the need for increased coordination of policy directions and regulatory activities both across the industries......Continuously expanding applications of information and communication technologies (ICT) are transforming local, national, regional and international economies into network economies, the foundation for information societies. They are being built upon expanded and upgraded national telecom networks...... to creating an environment to foster a massive expansion in the coverage and capabilities of the information infrastructure networks, with national telecom regulators as the key implementers of the policies of reform. The first phase of reform has focused on industry specific telecom policy and regulation...

  2. The regulator's view

    International Nuclear Information System (INIS)

    Spanish experience holds a relatively important position in the field of the decommissioning of nuclear and radioactive facilities. Nuclear facilities are subject to a system of prior authorization by the competent authorities before they come into service and to subsequent regulation and control during their operating life. Nuclear and radioactive facilities that stop operating, for technical or financial reasons or because they are compelled to, remain subject to this regulatory control system as long as the competent authorities consider that their residual radioactivity represents a potential source of radiological hazard to the individuals affected or entails an unacceptable environmental risk. The decommissioning of nuclear facilities is contemplated in Spain a further or an additional step of their life cycle in which, in principle, the whole regulatory framework in force during the previous stages - sitting, construction, commissioning, operation, etc. - remains applicable. The term decommissioning is used to delineate the final stage of the life of a definitely non-operational facility and also to introduce a new licensing regime and a new regulatory control scheme. In the regulatory context, the decommissioning of a facility is understood as a set of administrative and technical actions and processes whose purpose, once a facility has been withdrawn from service, is to release it from regulatory control and so to relieve the former licensee of its previous responsibilities relating to the facility's safety. With the increasing age of nuclear and radioactive facilities in service, and as the number of facilities reaching the end of their operating life rises, the administrative process required in order to decommissioning them safely has become a real challenge in all countries, especially in those like Spain with an old nuclear power programme. Let me first give you a quick overview of the Spanish regulatory decommissioning framework. Then I will try to

  3. Regulated electricity retailing in Chile

    Energy Technology Data Exchange (ETDEWEB)

    Galetovic, Alexander, E-mail: alexander@galetovic.cl [Facultad de Ciencias Economicas y Empresariales, Universidad de los Andes, Santiago, Chile. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago (Chile); Munoz, Cristian M., E-mail: cmunozm@aes.com [AES Gener and Departamento de Ingenieria Electrica, Universidad Catolica de Chile (Chile)

    2011-10-15

    While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: > We review Chile's experience with regulated electricity retailing. > Distortions emerge when energy wholesale prices are volatile and prices stabilized. > Regulated retailers gain little by mitigating or correcting distortions. > Sometimes price distortions increase retailers' profits. > We estimate the cost of three distortions, which retailers have not corrected.

  4. Regulated electricity retailing in Chile

    International Nuclear Information System (INIS)

    While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: → We review Chile's experience with regulated electricity retailing. → Distortions emerge when energy wholesale prices are volatile and prices stabilized. → Regulated retailers gain little by mitigating or correcting distortions. → Sometimes price distortions increase retailers' profits. → We estimate the cost of three distortions, which retailers have not corrected.

  5. Grandfather regulations, new source bias, and state air toxics regulations

    International Nuclear Information System (INIS)

    This paper uses plant-level data from the Census of Manufactures and the variation in toxic air pollution regulations across states to measure the effects of laws that are more stringent for new sources of pollution than for existing sources (so-called 'grandfather' regulations). Of particular interest is the resulting 'new source bias' and its effects on capital vintage and investment. Two industries are examined: commercial printing, which has a local product market; and paint manufacturing, which has a more national market. In general, there seem to be no statistically significant differences in capital vintage or investment between plants in states that grandfather new sources of pollution, plants in states that have no air toxics regulations, and plants in states that regulate both new and existing sources

  6. Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila.

    Science.gov (United States)

    Dollar, Gretchen; Gombos, Rita; Barnett, Austen A; Sanchez Hernandez, David; Maung, Saw M T; Mihály, Jozsef; Jenny, Andreas

    2016-03-01

    The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts. PMID:26801180

  7. Nanometrology - challenges for health regulation

    Directory of Open Access Journals (Sweden)

    Jailton Carreteiro Damasceno

    2013-11-01

    Full Text Available The relationship between metrology, nanotechnology and nanoscience and sanitary regulation is discussed from the point of view of its importance and the interrelationship between the themes for the development of products and services involving nanotech-nology. The discussion involves the main techniques for measuring dimensional, chemical and biological properties of materials, and presents some of the challenges for the future. Issues such as processes of standardization and regulation in Europe, U.S. and Brazil are also addressed, providing an overview of how these processes are related to sanitary regulation.

  8. Introduction to international radio regulations

    International Nuclear Information System (INIS)

    These lecture notes contain an overview of basic problems of the International Radio Regulations. Access to the existing information infrastructure, and to that of the future Information Society, depends critically on radio, especially in poor, remote and sparsely populated regions with under-developed telecommunication infrastructure. How the spectrum of radio frequencies is regulated has profound impact on the society, its security, prosperity, and culture. The radio regulations represent a very important framework for an adequate use of radio and should be known by all of those working in the field

  9. Designing Next Generation Telecom Regulation

    DEFF Research Database (Denmark)

    Henten, Anders; Samarajiva, Rohan; Melody, William H.

    2003-01-01

    This article critically examines the multiple rationales for telecom, IT, media convergence regulation, on the one hand, and multisector utility regulation, on the other, and the practical questions of implementation they pose, with a view to contributing to informed policy and regulatory decisions...... to the regulatory process such as scarcity of regulatory resources and safeguards for regulatory independence, are examined. It is concluded that ICT and media convergence issues are primarily about improving the efficiency of market economies, and how changes in regulation can facilitate this process. Multi...

  10. PTEN Phosphatase-Independent Maintenance of Glandular Morphology in a Predictive Colorectal Cancer Model System

    Directory of Open Access Journals (Sweden)

    Ishaan C. Jagan

    2013-11-01

    Full Text Available Organotypic models may provide mechanistic insight into colorectal cancer (CRC morphology. Three-dimensional (3D colorectal gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN coupling of cell division cycle 42 (cdc42 to atypical protein kinase C (aPKC. This study investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic functions in 3D models and assessed translational relevance in human studies. Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In translational studies, apical aPKC activity readout was assessed against apical membrane (AM orientation and gland morphology in 3D models and human CRC. We found that catalytically active or inactive PTEN constructs containing an intact C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium binding region 3 membrane-binding loop (M-CBR3 were ineffective. The isolated PTEN C2 domain (C2 accumulated in membrane fractions, but C2 M-CBR3 remained in cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of apical phospho-aPKC correlated with that of Na+/H+ exchanger regulatory factor-1 (NHERF-1 in the 3D model. Apical NHERF-1 intensity thus provided readout of apical aPKC activity and associated with glandular morphology in the model system and human colon. Low apical NHERF-1 intensity in CRC associated with disruption of glandular architecture, high cancer grade, and metastatic dissemination. We conclude that the membrane-binding function of the catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics and gland formation in a highly relevant 3D CRC morphogenesis model system.

  11. Radiation-Induced RhoGDIβ Cleavage Leads to Perturbation of Cell Polarity: A Possible Link to Cancer Spreading.

    Science.gov (United States)

    Fujiwara, Mamoru; Okamoto, Mayumi; Hori, Masato; Suga, Hiroshi; Jikihara, Hiroshi; Sugihara, Yuka; Shimamoto, Fumio; Mori, Toshio; Nakaoji, Koichi; Hamada, Kazuhiko; Ota, Takahide; Wiedemuth, Ralf; Temme, Achim; Tatsuka, Masaaki

    2016-11-01

    The equilibrium between proliferation and apoptosis is tightly balanced to maintain tissue homeostasis in normal tissues and even in tumors. Achieving and maintaining such a balance is important for cancer regrowth and spreading after cytotoxic treatments. Caspase-3 activation and tumor cell death following anticancer therapy as well as accompanying cell death pathways are well characterized, but their association to homeostasis of cancerous tissue and tumor progression remains poorly understood. Here we proposed a novel mechanism of cancer spreading induced by caspase-3. RhoGDIβ, known as a direct cleavage substrate of caspase-3, is overexpressed in many epithelial cancers. The N-terminal-truncated RhoGDIβ (ΔN-RhoGDIβ) is accumulated in caspase-3-activated cells. Stable expression of ΔN-RhoGDIβ in HeLa cells did not induce apoptosis, but impaired directional cell migration in a wound-healing assay accompanied by a perturbed direction of cell division at the wound edge. Subcellular protein fractionation experiments revealed that ΔN-RhoGDIβ but not wild-type RhoGDIβ was present in the detergent-soluble cytoplasmic and nuclear fractions and preferentially associated with Cdc42. Furthermore, Cdc42 activity was constitutively inhibited by stable expression of ΔN-RhoGDIβ, resulting in increased radiation-induced compensatory proliferation linking to RhoA activation. Thus, ΔN-RhoGDIβ dominant-negatively regulates Cdc42 activity and contributes to loss of polarity-related functions. The caspase-3-cleaved RhoGDIβ is a possible determinant to promote cancer spreading due to deregulation of directional organization of tumor cell population and inhibition of default equilibrium between proliferation and apoptosis after cytotoxic damage. J. Cell. Physiol. 231: 2493-2505, 2016. © 2016 Wiley Periodicals, Inc. PMID:26919575

  12. FDA 101: Regulating Biological Products

    Science.gov (United States)

    ... and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to Z ... public health needs enforces regulations to prevent the introduction or spread of communicable diseases within the country ...

  13. Comparison of some European regulations

    Energy Technology Data Exchange (ETDEWEB)

    Argyriadis, K. [Germanisher Lloyd, Hamburg (Germany)

    1996-09-01

    Fatigue calculations are an essential part in certification of a wind turbine. Manufacturers have to fulfill recommendations of several different regulations throughout Europe with the result that the design has often to be altered to satisfy them. In general three national (D/GL, NL, DK), and two international (GL, IEC) regulations are in use, with the IEC standard getting more importance with wind energy deploying to more in regions with no yet clearly defined national standards (India, Spain). The Germanischer Lloyd made calculations for wind turbines they are certifying and in one case we compared the resulting damages for different regulations and classes on a 600 kW, three bladed, stall regulated wind turbine. (EG) 18 refs.

  14. PDH regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian

    state is determined by the overall content / activity of the regulatory proteins PDH kinase (PDK), of which there are 4 isoforms, and PDH phosphatase (PDP), of which there are 2 isoforms. The overall aim of the PhD project was to elucidate 4 issues. 1: Role of muscle type in resting and exercise......-induced PDH regulation in human skeletal muscle. 2: Effect of muscle glycogen on PDH regulation in human skeletal muscle at rest and during exercise. 3: The impact of physical inactivity on PDH regulation in human skeletal muscle at rest and during exercise. 4: Elucidating the importance of PGC-1? in PDH...... regulation in mouse skeletal muscle at rest and in response to fasting and during recovery from exercise. The studies indicate that the content of PDH-E1? in human muscle follows the metabolic profile of the muscle, rather than the myosin heavy chain fiber distribution of the muscle. The larger lactate...

  15. EPA's Environmental Laws and Regulations

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web page provides access to search and read the environmental laws and regulations related to EPA's mission. Regulatory guidance documents and rulemaking...

  16. Hydrography - Boating Special Regulation Streams

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This layer contains those streams/rivers within Pennsylvania that have specifc special regulations related to boating as defined by the Pennsylvania Fish and Boat...

  17. Network Regulation and Support Schemes

    DEFF Research Database (Denmark)

    Ropenus, Stephanie; Schröder, Sascha Thorsten; Jacobsen, Henrik

    2009-01-01

    -in tariffs to market-based quota systems, and network regulation approaches, comprising rate-of-return and incentive regulation. National regulation and the vertical structure of the electricity sector shape the incentives of market agents, notably of distributed generators and network operators....... This article seeks to investigate the interactions between the policy dimensions of support schemes and network regulation and how they affect the deployment of distributed generation. Firstly, a conceptual analysis examines how the incentives of the different market agents are affected. In particular......, it will be shown that there frequently exists a trade-off between the creation of incentives for distributed generators and for distribution system operators to facilitate the integration of distributed generation. Secondly, the interaction of these policy dimensions is analyzed, including case studies based...

  18. Electronic Code of Federal Regulations

    Data.gov (United States)

    National Archives and Records Administration — The Electronic Code of Federal Regulations (e-CFR) is the codification of the general and permanent rules published in the Federal Register by the executive...

  19. Regulations concerning nuclear facilities decommissioning

    International Nuclear Information System (INIS)

    After a short presentation of the French nuclear regulations, a short overview of their application is given. Finally, are presented the points related to the fiscality specific of nuclear basis facilities

  20. Automated Negotiation for Traffic Regulation

    OpenAIRE

    Gaciarz, Matthis; Aknine, Samir; BHOURI, Neila

    2015-01-01

    Urban congestion is a major problem in our society for quality of life and for productivity. The increasing communication abilities of vehicles and recent advances in artificial intelligence allow new solutions to be considered for traffic regulation, based on real-time information and distributed cooperative decision-making models. The paper presents a mechanism allowing a distributed regulation of the right-of-way of the vehicles at an intersection. The decision-making relies on an automati...

  1. How should Bitcoin be regulated ?

    OpenAIRE

    SHCHERBAK, Sergii

    2014-01-01

    The lack of clarity about Bitcoin’s legal framework has meant that none of the regulators across the EU have yet achieved sufficient clarity in the legal treatment of Bitcoin and its stakeholders. This uncertainty poses a number of substantial risks to Bitcoin stakeholders and creates challenges for regulatory authorities. Therefore, there is a need for a clear strategy for Bitcoin’s regulation aiming to ensure the maximum possible balance between the interests of Bitcoin stakeholders longing...

  2. Money laundering and its regulations

    OpenAIRE

    Chong, Alberto; López-de-Silanes, Florencio

    2007-01-01

    The recent wave of terrorist attacks has increased the attention paid to money laundering activities. Using several methodologies, this paper investigates empirically the determinants of money laundering and its regulation in over 80 countries by assembling a cross-country dataset on proxies for money laundering and the prevalence of feeding activities. The paper additionally constructs specific money laundering regulation indices based on available information on laws and their mechanisms of...

  3. Money Laundering and its Regulation

    OpenAIRE

    Chong, Alberto E.; Florencio López-de-Silanes

    2007-01-01

    The recent wave of terrorist attacks has increased the attention paid to money laundering activities. Using several methodologies, this paper investigates empirically the determinants of money laundering and its regulation in over 80 countries by assembling a cross-country dataset on proxies for money laundering and the prevalence of feeding activities. The paper additionally constructs specific money laundering regulation indices based on available information on laws and their mechanisms of...

  4. BIOTECHNOLOGY REGULATIONS AND THE WTO

    OpenAIRE

    Sheldon, Ian M.; Josling, Timothy E.

    2002-01-01

    This paper examines the regulation of trade in genetically modified organisms (GMOs) by the World Trade Organization (WTO). Despite rapid adoption of GMOs by a few exporters, many importers have developed relatively restrictive procedures for pre-market approval of GMOs, and are introducing mandatory labeling. While exporters have yet to seek a ruling from the WTO on these regulations, a trade dispute over GMOs is likely to occur before too long. Exporting countries will likely argue that imp...

  5. Emotion regulation and sport performance

    OpenAIRE

    Wagstaff, Chris

    2014-01-01

    This study used a single-blind, within-participant, counterbalanced, repeated-measures design to examine the relationship between emotional self-regulation and sport performance. Twenty competitive athletes completed four laboratory-based conditions; familiarization, control, emotion suppression, and nonsuppression. In each condition participants completed a 10-km cycling time trial requiring self-regulation. In the experimental conditions participants watched an upsetting video before perfor...

  6. Regulation and Corporate Board Composition

    OpenAIRE

    Staubo, Siv

    2014-01-01

    This thesis is in the field of corporate governance. The corporate governance structure involves laws, rules, and regulations on the distribution of rights and responsibilities among the different stakeholders in the firm. Due to several financial crises in the late 1990s and early 2000s, there has been an increased interest in the regulation of corporate governance. In particular, the composition of the corporate board has achieved extensive attention. The first essay in the thesis inve...

  7. Civilsamfundets ABC: R for Regulering

    DEFF Research Database (Denmark)

    Meyer, Gitte; Lund, Anker Brink

    2016-01-01

    Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering.......Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering....

  8. Corporate governance and banking regulation

    OpenAIRE

    Alexander, Kern

    2004-01-01

    The globalisation of banking markets has raised important issues regarding corporate governance regulation for banking institutions. This research paper addresses some of the major issues of corporate governance as it relates to banking regulation. The traditional principal-agent framework will be used to analyse some of the major issues involving corporate governance and banking institutions. It begins by analysing the emerging international regime of bank corporate governance. This has been...

  9. Quality of government regulated goods

    OpenAIRE

    Moszoro, Marian

    2010-01-01

    Regulators face the difficult task of determining the sets of price and quality of government-regulated goods. While the profit-maximizing monopoly always produces less in quantity than under free competition, the level of quality produced by the monopoly is not unequivocal: it depends on its cost and demand functions. The social effect of quality change is not unequivocal either, because it depends, apart from the cost function change, on the shift and tilt change of the demand curve. The pr...

  10. Regulating Power from Supermarket Refrigeration

    DEFF Research Database (Denmark)

    O'Connell, Niamh; Madsen, Henrik; Pinson, Pierre;

    2014-01-01

    This paper presents an analysis of the demand response capabilities of a supermarket refrigeration system, with a particular focus on the suitability for participation in the regulating power market. An ARMAX model of a supermarket refrigeration system is identified using experimental data from t...... represented in a manner that is sufficiently simple to communicate to a market operator in the form of a bid for the provision of regulating power....

  11. Dividend Policy in Regulated Firms

    OpenAIRE

    rondi, laura; Cambini, Carlo; bremberger, francisca; GUGLER, Klaus

    2013-01-01

    We study the impact of different regulatory and ownership regimes on the dividend policy of regulated firms. Using a panel of 106 publicly traded European electric utilities in the period 1986-2010, we link payout and smoothing decisions to the implementation of different regulatory mechanisms (cost plus vs. incentive regulation) and to firm ownership (state vs. private). After controlling for the potential endogeneity of the regulatory mechanism, our results show that utilities subject to i...

  12. International Competitiveness and Environmental Regulations

    OpenAIRE

    Babool, Md. Ashfaqul Islam; Michael R. Reed

    2005-01-01

    This study follows the standard factor endowment approach to explain the effects of environmental regulations on net exports in different product-based industries. It constructs an econometric model which includes factor endowments and environmental regulations to examine how strict environmental policy impact export competitiveness. Cross-sectional and time series (panel) data for 6 countries and 17 years were used in this model. In this study, capital services increase net exports in labor-...

  13. Environmental regulation and technology transfers

    OpenAIRE

    Asano, Takao; Matsushima, Noriaki

    2012-01-01

    This paper analyzes the situation in which a national government introduces environmental regulations. Within the framework of an international duopoly with environmental regulations, this paper shows that an environmental tax imposed by the government in the home country can induce a foreign firm with advanced abatement technology to license it to a domestic firm without this technology. Furthermore, when the domestic firm's production technology is less efficient than that of the foreign fi...

  14. Precision Adjustable Liquid Regulator (ALR)

    Science.gov (United States)

    Meinhold, R.; Parker, M.

    2004-10-01

    A passive mechanical regulator has been developed for the control of fuel or oxidizer flow to a 450N class bipropellant engine for use on commercial and interplanetary spacecraft. There are several potential benefits to the propulsion system, depending on mission requirements and spacecraft design. This system design enables more precise control of main engine mixture ratio and inlet pressure, and simplifies the pressurization system by transferring the function of main engine flow rate control from the pressurization/propellant tank assemblies, to a single component, the ALR. This design can also reduce the thermal control requirements on the propellant tanks, avoid costly Qualification testing of biprop engines for missions with more stringent requirements, and reduce the overall propulsion system mass and power usage. In order to realize these benefits, the ALR must meet stringent design requirements. The main advantage of this regulator over other units available in the market is that it can regulate about its nominal set point to within +/-0.85%, and change its regulation set point in flight +/-4% about that nominal point. The set point change is handled actively via a stepper motor driven actuator, which converts rotary into linear motion to affect the spring preload acting on the regulator. Once adjusted to a particular set point, the actuator remains in its final position unpowered, and the regulator passively maintains outlet pressure. The very precise outlet regulation pressure is possible due to new technology developed by Moog, Inc. which reduces typical regulator mechanical hysteresis to near zero. The ALR requirements specified an outlet pressure set point range from 225 to 255 psi, and equivalent water flow rates required were in the 0.17 lb/sec range. The regulation output pressure is maintained at +/-2 psi about the set point from a P (delta or differential pressure) of 20 to over 100 psid. Maximum upstream system pressure was specified at 320 psi

  15. Balancing Public and Private Regulation

    Directory of Open Access Journals (Sweden)

    Martijn Scheltema

    2016-01-01

    Full Text Available Voluntary Sustainability Standards (VSS might develop into a viable alternative to public regulation. However, it turns on the (regulatory circumstances whether that holds true in practice. If public regulation on CSR topics is lacking, governments are unable to agree upon certain topics on a global level or diverging public regulation exists, VSS can be helpful to set global standards. Obviously, private standards will especially be helpful if they are commensurate with local public legislation (and e.g. treaties and/or are accepted by local governments. If one neglects this, numerous domestic structures might exist that frustrate VSS. Furthermore, governments have to remain vigilant as to whether these private regimes do not result in market disruption, consumer detriment or hamper trade. VSS might also compete with public arrangements which might limit the uptake of VSS. However, if public regulation exists VSS might be a viable alternative if compliance with not too compelling public norms by market participants is rather poor and the public policymaker is aiming to incentivize the better performing part of the market to embark on higher standards and thus only desires to regulate the less performing part of the market. However, of paramount importance is the effectiveness of VSS in order to be a viable alternative to public regulation. The effectiveness of VSS should be assessed using an integrated multi-disciplinary (comparative approach entailing legal, impact-assessment, legitimacy, governance and behavioural aspects. Only effective VSS in the aforementioned sense are a true alternative to public regulation.Beyond that, the legal perspective in connection with (the effectiveness of VSS is discussed, featuring FSC and UTZ Certified as an example. It is important from this perspective that VSS have a clear and sufficiently selective objective and sufficiently specific norms, are regularly evaluated, entail ‘conflict of law rules’ and

  16. Drinking Water Contaminants -- Standards and Regulations

    Science.gov (United States)

    ... Facebook Twitter Google+ Pinterest Contact Us Drinking Water Contaminants – Standards and Regulations The Environmental Protection Agency (EPA) ... tribes, and many other partners. Regulated Drinking Water Contaminants National Primary Drinking Water Regulations (NPDWRs) - table of ...

  17. Basic Regulations for All Food Processors

    OpenAIRE

    Bacon, Karleigh

    2012-01-01

    There are some basic regulations that are required for all food processing facilities to follow. These regulations are current Good Manufacturing Practices (GMPs) and/or Sanitation Standard Operation Procedures (SSOP's). This guidesheet provides links to further information and regulations.

  18. 77 FR 43082 - Federal Acquisition Regulation; Information Collection; Commerce Patent Regulations

    Science.gov (United States)

    2012-07-23

    ... Regulation; Information Collection; Commerce Patent Regulations AGENCIES: Department of Defense (DOD... approved information collection requirement concerning Department of Commerce patent regulations. Public...: Submit comments identified by Information Collection 9000- 0095, Commerce Patent Regulations, by any...

  19. A Model of Endogeneous Oil Spill Regulation

    OpenAIRE

    Ayla Ogus

    2005-01-01

    This paper presents a model of endogenous oil spill regulation where the severity of regulations is shown to be a function of the size of recent spills. The regulator chooses how much to regulate in order to maximize political capital when regulations are rigid downwards and the distribution of spills is not known with certainty. Very large spills are shown to cause large increases in the regulation level. In the event that an unlikely disastrous spill is realized, major regulatory reform may...

  20. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

  1. Progress toward risk informed regulation

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, K.C.

    1997-01-01

    For the last several years, the NRC, with encouragement from the industry, has been moving in the direction of risk informed regulation. This is consistent with the regulatory principle of efficiency, formally adopted by the Nuclear Regulatory Commission in 1991, which requires that regulatory activities be consistent with the degree of risk reduction they achieve. Probabilistic risk analysis has become the tool of choice for selecting the best of several alternatives. Closely related to risk informed regulation is the development of performance based rules. Such rules focus on the end result to be achieved. They do not specify the process, but instead establish the goals to be reached and how the achievement of those goals is to be judged. The inspection and enforcement activity is based on whether or not the goals have been met. The author goes on to offer comments on the history of the development of this process and its probable development in the future. He also addresses some issues which must be resolved or at least acknowledged. The success of risk informed regulation ultimately depends on having sufficiently reliable data to allow quantification of regulatory alternatives in terms of relative risk. Perhaps the area of human reliability and organizational performance has the greatest potential for improvement in reactor safety. The ability to model human performance is significantly less developed that the ability to model mechanical or electrical systems. The move toward risk informed, performance based regulation provides an unusual, perhaps unique, opportunity to establish a more rational, more effective basis for regulation.

  2. Molecular regulation of osteoclast activity.

    Science.gov (United States)

    Bruzzaniti, Angela; Baron, Roland

    2006-06-01

    Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed. PMID:16951988

  3. Explaining (Missing) Regulator Paradigm Shifts

    DEFF Research Database (Denmark)

    Wigger, Angela; Buch-Hansen, Hubert

    2014-01-01

    regulation after the crisis in the 1970s, the paper argues that the preconditions for a fundamental shift in this issue area are not present this time around. Several reasons account for this: the current crisis has been construed by economic and political elites as a crisis within and not of neoliberal......The global financial and economic crisis has prompted some scholars to suggest that a fundamental regulatory shift away from neoliberalism will take place – both in general and in the field of EU competition regulation. This paper shows that so far no radical break with the neoliberal type of...... competition regulation is heaving into sight. It sets out to explain this from the vantage point of a critical political economy perspective, which identifies the circumstances under which a crisis can result in a regulatory paradigm shift. Contrasting the current situation with the shift in EC/EU competition...

  4. Developmental regulators in Aspergillus fumigatus.

    Science.gov (United States)

    Park, Hee-Soo; Yu, Jae-Hyuk

    2016-03-01

    The filamentous fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. This fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. The initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousands of genes associated with formation of the asexual developmental structure conidiophore, and biogenesis of conidia. In this review, we summarize key regulators that directly or indirectly govern conidiation in this important pathogenic fungus. Better understanding these developmental regulators may provide insights into the improvement in controlling both beneficial and detrimental aspects of various Aspergillus species. PMID:26920882

  5. Decisions to regulate genotoxic substances

    International Nuclear Information System (INIS)

    Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

  6. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  7. Wave Dragon Buoyancy Regulation Study

    DEFF Research Database (Denmark)

    Jakobsen, Jens; Kofoed, Jens Peter

    Wave Dragon is a wave energy converter, which was deployed offshore at Nissum Bredning in Denmark in 2003. The experience gained from operating Wave Dragon during 2003 and 2004 has shown that the buoyancy regulation system can be improved in a number of ways. This study describes the current...... situation, and proposes a number of activities in order to improve the buoyancy regulation system. This work was performed under EU ENERGIE contract no. ENK5-CT-2002-00603, and is a contribution to WP 2.3/2.4 and D40/D41....

  8. Introduction to international radio regulations

    International Nuclear Information System (INIS)

    These notes introduce the ITU Radio Regulations and related UN and WTO agreements that specify how terrestrial and satellite radio should be used in all countries over the planet. Access to the existing information infrastructure, and to that of the future Information Society, depends critically on these regulations. The paper also discusses few problems related to the use of the radio frequencies and satellite orbits. The notes are extracted from a book under preparation, in which these issues are discussed in more detail. (author)

  9. Scambio, a novel guanine nucleotide exchange factor for Rho

    Directory of Open Access Journals (Sweden)

    Groffen John

    2004-04-01

    Full Text Available Abstract Background Small GTPases of the Rho family are critical regulators of various cellular functions including actin cytoskeleton organization, activation of kinase cascades and mitogenesis. For this reason, a major objective has been to understand the mechanisms of Rho GTPase regulation. Here, we examine the function of a novel protein, Scambio, which shares homology with the DH-PH domains of several known guanine nucleotide exchange factors for Rho family members. Results Scambio is located on human chromosome 14q11.1, encodes a protein of around 181 kDa, and is highly expressed in both heart and skeletal muscle. In contrast to most DH-PH-domain containing proteins, it binds the activated, GTP-bound forms of Rac and Cdc42. However, it fails to associate with V14RhoA. Immunofluorescence studies indicate that Scambio and activated Rac3 colocalize in membrane ruffles at the cell periphery. In accordance with these findings, Scambio does not activate either Rac or Cdc42 but rather, stimulates guanine nucleotide exchange on RhoA and its close relative, RhoC. Conclusion Scambio associates with Rac in its activated conformation and functions as a guanine nucleotide exchange factor for Rho.

  10. The Organization of Regulated Production

    DEFF Research Database (Denmark)

    Jansen, Jos; Jeon, Doh-Shin; Menicucci, Domenico

    2008-01-01

    weak positive (respectively, strong positive) correlation. Second, if the firms can collude under VS and know all costs, then VS is equivalent to VI. However, if firms collude under asymmetric information, then collusion does not affect the choice between VS and VI, since the regulator takes advantage...

  11. Incentives and regulation in banking

    NARCIS (Netherlands)

    N. Martynova

    2015-01-01

    The financial crisis of 2007-2008 has unveiled the hidden flaws in the regulatory framework of the financial sector. The rules of the game established by regulators were not stringent enough and provided bankers with wrong incentives to gamble with depositors’ money. There are two major challenges i

  12. Liquidity regulation and bank behavior

    NARCIS (Netherlands)

    Bonner, C.

    2014-01-01

    In response to the 2007-08 financial crisis, the Basel Committee on Banking Supervision proposed two liquidity standards to reinforce banks’ resilience to liquidity risks. The purpose of this thesis is to analyze the impact of liquidity regulation on bank behavior. The first of four main chapters an

  13. New Zealand's financial sector regulation

    OpenAIRE

    Geof Mortlock

    2003-01-01

    This article provides a summary of the regulatory framework in the New Zealand financial sector. It describes the core components of the financial system, including the financial institutions and financial markets, and explains the infrastructure required to support the system. The article then discusses the main aspects of the regulatory framework of the financial system, particularly banking supervision and securities market regulation.

  14. Endocannabinoid Signaling Regulates Sleep Stability

    OpenAIRE

    Pava, Matthew J.; Alexandros Makriyannis; Lovinger, David M.

    2016-01-01

    The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid t...

  15. Regulating energy levies under discussion

    International Nuclear Information System (INIS)

    In the last two years several institutes advised on a regulating levy for energy. Several variants are compared and the critical remarks are analyzed. In particular a progressive levy, as suggested by the Dutch Scientific Council for the Government Policy (WRR, abbreviated in Dutch), opens new perspectives. 1 tab., 27 refs

  16. Contextuality: Wheeler's universal regulating principle

    CERN Document Server

    Durham, Ian T

    2013-01-01

    In this essay I develop quantum contextuality as a potential candidate for Wheeler's universal regulating principle, arguing -- \\textit{contrary} to Wheeler -- that this ultimately implies that `bit' comes from `it.' In the process I develop a formal definition of physical determinism in the languages of domain theory and category theory.

  17. Phytochrome-regulated Gene Expression

    Institute of Scientific and Technical Information of China (English)

    Peter H. Quail

    2007-01-01

    Identification of all genes involved in the phytochrome (phy)-mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-regulated genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an initial subset of these genes. The data: (a) reveal considerable complexity in the channeling of the light signals through the different phy-family members (phyA to phyE) to responsive genes; (b) identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, and, therefore, as potentially important regulators in the transcriptional-network hierarchy; and (c) identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetiolation.

  18. Regulating Collaboration in Teacher Education

    Science.gov (United States)

    Dobber, Marjolein; Akkerman, Sanne F.; Verloop, Nico; Vermunt, Jan D.

    2014-01-01

    Collaboration in teacher education can be seen as a way to prepare student teachers for future social practices at school. When people collaborate with each other, they have to regulate their collaboration. In the Dutch teacher education programme that was investigated, student teachers were members of different types of groups, each of which had…

  19. Deceptive Business Practices: State Regulations.

    Science.gov (United States)

    Rohrer, Daniel Morgan

    Although much has been done at the federal level to control deceptive advertising practices, many states have no criminal laws designed to regulate advertising, and several states recently repealed such laws. This paper examines states' efforts to balance the advertiser's freedom of speech with the consumer's need for information about products by…

  20. Regulation of microtubule dynamic instability

    NARCIS (Netherlands)

    B. van der Vaart (Babet); A.S. Akhmanova (Anna); A. Straube (Anne)

    2009-01-01

    textabstractProper regulation of MT (microtubule) dynamics is essential for various vital processes, including the segregation of chromosomes, directional cell migration and differentiation. MT assembly and disassembly is modulated by a complex network of intracellular factors that co-operate or ant

  1. Mechanisms of Hsp90 regulation

    Science.gov (United States)

    Prodromou, Chrisostomos

    2016-01-01

    Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated. PMID:27515256

  2. Guidelines on Building Regulations 2008

    DEFF Research Database (Denmark)

    Authority. The Guidelines refer the reader to sources such as relevant standards, instructions and other background material which provides more detailed information. The Guidelines cover the same ground as BR08, including building control regulations, layout, fitting out, structures, fire safety, indoor...

  3. Temperature: Human Regulating, Ants Conforming

    Science.gov (United States)

    Clopton, Joe R.

    2007-01-01

    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  4. Regulation of the fungal secretome.

    Science.gov (United States)

    McCotter, Sean W; Horianopoulos, Linda C; Kronstad, James W

    2016-08-01

    The ability of countless representatives of the Kingdom Fungi to adapt to and proliferate in diverse environments is facilitated by regulation of their secretomes to respond to changes in environmental conditions and to mediate interactions with other organisms. Secretome changes often fulfill common functions of nutrient acquisition, facilitation of host/symbiont interactions, cell wall modification, and optimization of the enzyme suite to adapt to new environmental resources. In this review, we expand on our recent work on signaling and the secretome in the pathogenic fungus Cryptococcus neoformans to consider a range of selected examples of regulation of fungal secretomes. These examples include the impact of carbon source and aspects of the response to plant and animal hosts. Additionally, the influence of key protein kinases (e.g., Pka1, Snf1) and transcription factors (e.g., Rim101/PacC) is highlighted to illustrate some underlying regulatory factors influencing the secretome. Although there is a wealth of information about fungal secretomes from both experimentation and genome sequence mining, there are also major gaps in our knowledge about the complete composition of fungal secretomes and mechanisms of dynamic change. For example, a more comprehensive understanding of the composition and regulation of the secretome will require consideration of the emerging roles of unconventional secretion and extracellular vesicles in delivering proteins outside the cell. Overall, changes in the secretome are well documented in diverse fungi and the underlying mechanisms are currently under investigation; however, there remain unknown steps in the regulation of secretory pathways and gaps in understanding the regulation of unconventional secretion, which warrant further research. PMID:26879194

  5. Natural Gas Distribution Regulation Natural Gas Distribution Regulation

    Directory of Open Access Journals (Sweden)

    Fernando Salas

    1995-03-01

    Full Text Available This document discusses the economic content of a set of Ruling affecting the provision of natural gas distribution services in Mexico. As such, it describes the mechanisms proposed in order to ensure economic efficiency in the undertaking of such activity, i.e., competition policies, rate regulation, delimination of licensed geographic regions and design of auction procedures for the granting of distribution franchises. This document discusses the economic content of a set of Ruling affecting the provision of natural gas distribution services in Mexico. As such, it describes the mechanisms proposed in order to ensure economic efficiency in the undertaking of such activity, i.e., competition policies, rate regulation, delimination of licensed geographic regions and design of auction procedures for the granting of distribution franchises.

  6. REGULATION OF INTESTINAL DYSBACTERIOSIS OF BURNED RATS BY MICROECOSYSTEM REGULATORS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the feasibility of using synbiotics and probiotics to prevent and cure intestinal dysbacteriosis after burn. Methods Burned rats were fed with synbiotics and probiotics reagents, and the amounts of major intestinal florae in caecal contents were detected. Results The major physiological anaerobes were mostly stable, and the conditioned pathogens had no abnormal. Conclusion The micro-ecosystem regulator can quickly supplement the decreased physiological anaerobes caused by burning,and avoid the occurrence of dysbacteriosis.

  7. IAEA regulations: originality within general regulations for dangerous materials transport

    International Nuclear Information System (INIS)

    Risks from transport of dangerous materials are briefly recalled. Safety of transport is improved by regulation aiming at the limitation of accident consequences. For radioactive material transport the safety is based on the packaging. Limitations of dose rate, labelling, type of packagings risk evaluation, transport operation, intervention in case of accidents are reviewed. A data bank is constituted and a research program is coordinated by the IAEA

  8. Natural Gas Distribution Regulation Natural Gas Distribution Regulation

    OpenAIRE

    Fernando Salas; Benjamín Contreras

    1995-01-01

    This document discusses the economic content of a set of Ruling affecting the provision of natural gas distribution services in Mexico. As such, it describes the mechanisms proposed in order to ensure economic efficiency in the undertaking of such activity, i.e., competition policies, rate regulation, delimination of licensed geographic regions and design of auction procedures for the granting of distribution franchises. This document discusses the economic content of a set of Ruling affectin...

  9. Regulating the regulators: modulators of transcription factor activity.

    Science.gov (United States)

    Everett, Logan; Hansen, Matthew; Hannenhalli, Sridhar

    2010-01-01

    Gene transcription is largely regulated by DNA-binding transcription factors (TFs). However, the TF activity itself is modulated via, among other things, post-translational modifications (PTMs) by specific modification enzymes in response to cellular stimuli. TF-PTMs thus serve as "molecular switchboards" that map upstream signaling events to the downstream transcriptional events. An important long-term goal is to obtain a genome-wide map of "regulatory triplets" consisting of a TF, target gene, and a modulator gene that specifically modulates the regulation of the target gene by the TF. A variety of genome-wide data sets can be exploited by computational methods to obtain a rough map of regulatory triplets, which can guide directed experiments. However, a prerequisite to developing such computational tools is a systematic catalog of known instances of regulatory triplets. We first describe PTM-Switchboard, a recent database that stores triplets of genes such that the ability of one gene (the TF) to regulate a target gene is dependent on one or more PTMs catalyzed by a third gene, the modifying enzyme. We also review current computational approaches to infer regulatory triplets from genome-wide data sets and conclude with a discussion of potential future research. PTM-Switchboard is accessible at http://cagr.pcbi.upenn.edu/PTMswitchboard / PMID:20827600

  10. Possibilities of Economic Regulations Modelling Using Computers

    Directory of Open Access Journals (Sweden)

    Algirdas Jakutis

    2011-04-01

    Full Text Available This article presents possibilities of using computers for economic regulations modelling. The introduction gives a computer history and shows possibilities to use computers in many different ways. Research on the combination of economic regulations is carried out. Human and computer functions using economic regulations are presented. Research shows modelling possibilities of economic regulations with computer, text editors, text editing options. The article also presents economic regulations modelling algorithms and programs.

  11. Epigenetic microRNA Regulation

    DEFF Research Database (Denmark)

    Wiklund, Erik Digman

    2011-01-01

    and confirming transcriptional start sites can be difficult. Epigenetics, gene regulatory and DNA modification mechanisms not involving a change to the primary sequence, have been implied in the regulation of a number of miRNA loci. Both epigenetic and miRNA signatures are broadly altered in cancer......, and are thought to play essential roles in cancer etiology and progression. Here, we aimed to identify epigenetic miRNA deregulation in bladder and oral carcinoma, and to develop a robust approach to epigenetic miRNA prediction and detection. In addition, non-canonical epigenetic functions directed by a nuclear...... miRNA were investigated. In summary, we report that the miR-200 family and miR-205 are coordinately epigenetically regulated in a variety of cell lines, tumors and normal tissues. MiR-200c expression is correlated with bladder cancer disease progression, and miR-375 levels in oral rinse can...

  12. The grammar of transcriptional regulation.

    Science.gov (United States)

    Weingarten-Gabbay, Shira; Segal, Eran

    2014-06-01

    Eukaryotes employ combinatorial strategies to generate a variety of expression patterns from a relatively small set of regulatory DNA elements. As in any other language, deciphering the mapping between DNA and expression requires an understanding of the set of rules that govern basic principles in transcriptional regulation, the functional elements involved, and the ways in which they combine to orchestrate a transcriptional output. Here, we review the current understanding of various grammatical rules, including the effect on expression of the number of transcription factor binding sites, their location, orientation, affinity and activity; co-association with different factors; and intrinsic nucleosome organization. We review different methods that are used to study the grammar of transcription regulation, highlight gaps in current understanding, and discuss how recent technological advances may be utilized to bridge them. PMID:24390306

  13. Endocrine regulation of circadian physiology.

    Science.gov (United States)

    Tsang, Anthony H; Astiz, Mariana; Friedrichs, Maureen; Oster, Henrik

    2016-07-01

    Endogenous circadian clocks regulate 24-h rhythms of behavior and physiology to align with external time. The endocrine system serves as a major clock output to regulate various biological processes. Recent findings suggest that some of the rhythmic hormones can also provide feedback to the circadian system at various levels, thus contributing to maintaining the robustness of endogenous rhythmicity. This delicate balance of clock-hormone interaction is vulnerable to modern lifestyle factors such as shiftwork or high-calorie diets, altering physiological set points. In this review, we summarize the current knowledge on the communication between the circadian timing and endocrine systems, with a focus on adrenal glucocorticoids and metabolic peptide hormones. We explore the potential role of hormones as systemic feedback signals to adjust clock function and their relevance for the maintenance of physiological and metabolic circadian homeostasis. PMID:27106109

  14. Nongenomic Mechanisms of PTEN Regulation

    Directory of Open Access Journals (Sweden)

    Jimmie E. Fata

    2012-01-01

    Full Text Available A large amount of data supports the view that PTEN is a bona fide tumor suppressor gene. However, recent evidence suggests that derailment of cellular localization and expression levels of functional nonmutated PTEN is a determining force in inducing abnormal cellular and tissue outcomes. As the cellular mechanisms that regulate normal PTEN enzymatic activity resolve, it is evident that deregulation of these mechanisms can alter cellular processes and tissue architecture and ultimately lead to oncogenic transformation. Here we discuss PTEN ubiquitination, PTEN complex formation with components of the adherens junction, PTEN nuclear localization, and microRNA regulation of PTEN as essential regulatory mechanisms that determine PTEN function independent of gene mutations and epigenetic events.

  15. Regulation by light in Fusarium.

    Science.gov (United States)

    Avalos, Javier; Estrada, Alejandro F

    2010-11-01

    The genus Fusarium stands out as research model for pathogenesis and secondary metabolism. Light stimulates the production of some Fusarium metabolites, such as the carotenoids, and in many species it influences the production of asexual spores and sexual fruiting bodies. As found in other fungi with well-known photoresponses, the Fusarium genomes contain several genes for photoreceptors, among them a set of White Collar (WC) proteins, a cryptochrome, a photolyase, a phytochrome and two presumably photoactive opsins. The mutation of the opsin genes produced no apparent phenotypic alterations, but the loss of the only WC-1 orthologous protein eliminated the photoinduced expression of the photolyase and opsin genes. In contrast to other carotenogenic species, lack of the WC photoreceptor did not impede the light-induced accumulation of carotenoids, but produced alterations in conidiation, animal pathogenicity and nitrogen-regulated secondary metabolism. The regulation and functional role of other Fusarium photoreceptors is currently under investigation. PMID:20460165

  16. Culture, emotion regulation, and adjustment.

    Science.gov (United States)

    Matsumoto, David; Yoo, Seung Hee; Nakagawa, Sanae

    2008-06-01

    This article reports differences across 23 countries on 2 processes of emotion regulation--reappraisal and suppression. Cultural dimensions were correlated with country means on both and the relationship between them. Cultures that emphasized the maintenance of social order--that is, those that were long-term oriented and valued embeddedness and hierarchy--tended to have higher scores on suppression, and reappraisal and suppression tended to be positively correlated. In contrast, cultures that minimized the maintenance of social order and valued individual Affective Autonomy and Egalitarianism tended to have lower scores on Suppression, and Reappraisal and Suppression tended to be negatively correlated. Moreover, country-level emotion regulation was significantly correlated with country-level indices of both positive and negative adjustment. PMID:18505309

  17. [Key regulators of skeletal myogenesis].

    Science.gov (United States)

    Kopantseva, E E; Belyavsky, A V

    2016-01-01

    Skeletal myogenesis has been extensively studied at both morphological and molecular levels. This review considers the main stages of embryonic skeletal myogenesis and myogenic factors that trigger their initiation, focusing on specific protein interactions involved in somitic myogenesis, head myogenesis, and limb myogenesis. The second part of the review describes the role of noncoding RNAs (microRNAs and long noncoding RNAs) in myogenesis. This information is of particular interest, because regulation of cell processes by noncoding RNAs is an actively developing field of molecular biology. Knowledge of mechanisms of skeletal myogenesis is of applied significance. Various transcription factors, noncoding RNAs, and other myogenic regulators can be employed in the induction of myogenic reprogramming in stem cells and differentiated somatic cells. Current trends and strategies in the field of skeletal myogenic reprogramming are discussed in the last part of the review. PMID:27239841

  18. Foresight and Public Utility Regulation.

    OpenAIRE

    Gort, Michael; Wall, Richard A

    1988-01-01

    This paper develops a model that shows the effects of rational expectations, and of efficient mark ets, on public utility regulation. It is shown that the feedback from investor expectations to regulatory behavior, together with investor expectations that take account of this feedback, basically alters th e consequences of regulatory decisions. The analysis examines the eff ects of a deviation between the allowed rate of return and the cost o f capital, with both perfect and imperfect investo...

  19. Financial Regulation in General Equilibrium

    OpenAIRE

    Goodhart, Ch. A. E.; Kashyap, A. K.; D. P. Tsomocos; Vardoulakis, A. P.

    2012-01-01

    This paper explores how different types of financial regulation could combat many of the phenomena that were observed in the financial crisis of 2007 to 2009. The primary contribution is the introduction of a model that includes both a banking system and a "shadow banking system" that each help households finance their expenditures. Households sometimes choose to default on their loans, and when they do this triggers forced selling by the shadow banks. Because the forced selling comes when ne...

  20. Funding regulations and risk sharing

    OpenAIRE

    Colin Pugh; Juan Yermo

    2008-01-01

    This paper provides a description of the risk sharing features of pension plan design in selected OECD and non-OECD countries and how they correspond with the funding rules applied to pension funds. In addition to leading to a better understanding of differences in funding rules across countries with developed pension fund systems, the study considers the trend towards risk-based regulation. While the document does not enter the debate over the application of riskbased quantitative funding re...

  1. Genetic disorders of phosphate regulation

    OpenAIRE

    Gattineni, Jyothsna; Baum, Michel

    2012-01-01

    Regulation of phosphate homeostasis is critical for many biological processes, and both hypophosphatemia and hyperphosphatemia can have adverse clinical consequences. Only a very small percentage (1%) of total body phosphate is present in the extracellular fluid, which is measured by routine laboratory assays and does not reflect total body phosphate stores. Phosphate is absorbed from the gastrointestinal tract via the transcellular route [sodium phosphate cotransporter 2b (NaPi2b)] and acros...

  2. Challenges in Regulating Pesticide Mixtures

    OpenAIRE

    Debra Denton; Bruce Hammock; Craig Wheelock; Jason Belden; Michael Lydy

    2004-01-01

    This paper introduces the field of mixture toxicity and the challenges in regulating pesticide mixtures. Even though pesticides are unique chemical stressors designed to have biological activity that can affect a number of nontarget species, they are intentionally placed into the environment in large quantities. Currently, methods and terminology for evaluating mixture toxicity are poorly established. The most common approach used is the assumption of additive concentration, with the concentr...

  3. The Empirics of Banking Regulation

    OpenAIRE

    Tchana Tchana, Fulbert

    2008-01-01

    This paper empirically assesses whether banking regulation is effective at preventing banking crises. We use a monthly index of banking system fragility, which captures almost every source of risk in the banking system, to estimate the effect of regulatory measures (entry restriction, reserve requirement, deposit insurance, and capital adequacy requirement) on banking stability in the context of a Markov-switching model. Our methodology is less prone to selection and simultaneity bias which a...

  4. Privacy Regulation and Online Advertising

    OpenAIRE

    Avi Goldfarb; Catherine E. Tucker

    2011-01-01

    Advertisers use online customer data to target their marketing appeals. This has heightened consumers' privacy concerns, leading governments to pass laws designed to protect consumer privacy by restricting the use of data and by restricting online tracking techniques used by websites. We use the responses of 3.3 million survey takers who had been randomly exposed to 9,596 online display (banner) advertising campaigns to explore how privacy regulation in the European Union (EU) has influenced ...

  5. Supporting self-regulated learning

    OpenAIRE

    Nussbaumer, Alexander; Dahn, Ingo; Kroop, Sylvana; Mikroyannidis, Alexander; Albert, Dietrich

    2015-01-01

    Self-regulated learning (SRL) competences are crucial for lifelong learning. Their cultivation requires the right balance between freedom and guidance during the learning processes. Current learning systems and approaches, such as personal learning environments, give overwhelming freedom, but also let weak learners alone. Other systems, such as learning management systems or adaptive systems, tend to institutionalise learners too much, which does not support the development of SRL competences...

  6. Emerging Issues in Banking Regulation

    OpenAIRE

    Sunil Sharma; Ralph Chami; Mohsin S. Khan

    2003-01-01

    The paper provides an overview of the profound and rapid changes in banking brought about by technology and deregulation, and discusses the hurdles that will have to be negotiated for putting in place the three pillars-capital adequacy rules, supervision, and market discipline-of the bank regulatory framework envisioned by the New Basel Accord (Basel II). It argues that, especially for developing countries, finding the right balance between regulation, supervision, and market discipline is li...

  7. The social Bases of Regulation

    OpenAIRE

    Bagnasco Arnaldo

    2010-01-01

    Deep changes occured in the social stratification of developed societies during the recent years of neo-liberal capitalism. The search of new institutional forms of social and economic regulation requires a prior understanding of some fundamental features of social change. Beginning by reconstructing the social bases of the old post-war social compromises, both in Europe and United States, the article investigates the stratification effects in processes such as "Flexible specialization", "New...

  8. Lipid Regulation of Acrosome Exocytosis.

    Science.gov (United States)

    Cohen, Roy; Mukai, Chinatsu; Travis, Alexander J

    2016-01-01

    Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the "DNA--RNA-protein" synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes-cholesterol, phospholipids, and the ganglioside G(M1)--in context of the modern paradigm of acrosome exocytosis. We describe how these various- species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis. PMID:27194352

  9. Human trafficking and regulating prostitution

    OpenAIRE

    Lee, Samuel; Persson, Petra

    2013-01-01

    We study sex trafficking in a marriage market model of prostitution. When traffickers can coerce women to sell sex, trafficked prostitutes constitute a non-zero share of supply in any unregulated market for sex. We ask if regulation can eradicate trafficking and restore the equilibrium that would arise in an unregulated market without traffickers. While all existing approaches – criminalization of prostitutes (“the traditional model”), licensed prostitution (“the Dutch model”), and criminaliz...

  10. Tbx1 regulates brain vascularization.

    Science.gov (United States)

    Cioffi, Sara; Martucciello, Stefania; Fulcoli, Filomena Gabriella; Bilio, Marchesa; Ferrentino, Rosa; Nusco, Edoardo; Illingworth, Elizabeth

    2014-01-01

    The transcription factor TBX1 is the major gene involved in 22q11.2 deletion syndrome (22q11.2DS). Using mouse models of these diseases, we have previously shown that TBX1 activates VEGFR3 in endothelial cells (EC), and that this interaction is critical for the development of the lymphatic vasculature. In this study, we show that TBX1 regulates brain angiogenesis. Using loss-of-function genetics and molecular approaches, we show that TBX1 regulates the VEGFR3 and DLL4 genes in brain ECs. In mice, loss of TBX1 causes global brain vascular defects, comprising brain vessel hyperplasia, enhanced angiogenic sprouting and vessel network disorganization. This phenotype is recapitulated in EC-specific Tbx1 conditional mutants and in an EC-only 3-dimensional cell culture system (matrigel), indicating that the brain vascular phenotype is cell autonomous. Furthermore, EC-specific conditional Tbx1 mutants have poorly perfused brain vessels and brain hypoxia, indicating that the expanded vascular network is functionally impaired. In EC-matrigel cultures, a Notch1 agonist is able to partially rescue microtubule hyperbranching induced by TBX1 knockdown. Thus, we have identified a novel transcriptional regulator of angiogenesis that exerts its effect in brain by negatively regulating angiogenesis through the DLL4/Notch1-VEGFR3 regulatory axis. Given the similarity of the phenotypic consequences of TBX1 mutation in humans and mice, this unexpected role of TBX1 in murine brain vascularization should stimulate clinicians to search for brain microvascular anomalies in 22q11.2DS patients and to evaluate whether some of the anatomical and functional brain anomalies in patients may have a microvascular origin. PMID:23945394

  11. Regulation of Lipolysis in Adipocytes

    OpenAIRE

    Duncan, Robin E.; Ahmadian, Maryam; Jaworski, Kathy; Sarkadi-Nagy, Eszter; Sul, Hei Sook

    2007-01-01

    Lipolysis of white adipose tissue triacylglycerol stores results in the liberation of glycerol and nonesterified fatty acids that are released into the vasculature for use by other organs as energy substrates. In response to changes in nutritional state, lipolysis rates are precisely regulated through hormonal and biochemical signals. These signals modulate the activity of lipolytic enzymes and accessory proteins, allowing for maximal responsiveness of adipose tissue to changes in energy requ...

  12. A Shot at Regulating Securitization

    OpenAIRE

    Kiff, John; Kisser, Michael

    2011-01-01

    In order to incentivize stronger issuer due diligence effort, European and U.S. authorities are amending securitization-related regulations to force issuers to retain an economic interest in the securitization products they issue. The idea is that if loan originators and securitizers have more skin in the game they will more diligently screen the loans they originate and securitize. This paper uses a simple model to explore the economics of equity and mezzanine tranche retention in the contex...

  13. Radiation Safety (Qualifications) Regulations 1980

    International Nuclear Information System (INIS)

    These Regulations, promulgated pursuant to the provisions of the Radiation Safety Act, 1975-1979, require persons engaged in activities involving radiation to pass a radiation safety examination or to possess an approved qualification in radiation. The National Health and Medical Research Council is authorised to exempt persons from compliance with these requirements or, conversely, to impose such requirements on persons other than those designated. (NEA)

  14. ENERGY REGULATION IN YOUNG PEOPLE

    OpenAIRE

    Dodd, Caroline J.

    2007-01-01

    Obesity in young people is now realised as a worldwide crisis of epidemic proportion. The aetiology of this disease suggests a disruption in regulation of energy at the population level, leading to a positive energy balance and excess adiposity. The relative contribution of food intake and physical inactivity remains to be elucidated. Treatment interventions have aimed to create a deficit in energy balance through manipulation of physical activity, behavioural components or, to a lesser exten...

  15. Modeling Auxin-regulated Development

    OpenAIRE

    Krupinski, Pawel; Jönsson, Henrik

    2010-01-01

    The phytohormone auxin plays an essential role in many aspects of plant growth and development. Its patterning, intercellular transport, and means of signaling have been extensively studied both in experiments and computational models. Here, we present a review of models of auxin-regulated development in different plant tissues. This includes models of organ initiation in the shoot apical meristem, development of vascular strands in leafs and stems, and auxin-related functioning in roots. The...

  16. Utility Regulators : Roles and Responsibilities

    OpenAIRE

    Smith, Warrick

    1997-01-01

    There are three main issues in defining a utility regulator's role: the scope of its coverage, its role in relation to ministers, and its role in relation to other regulatory entities such as the competition agency or agencies dealing with environment or health and safety. The author makes a case for multi-industry agencies covering everything from power to water to transport. Multi-industry ...

  17. Hybrid Voltage Regulator for Automobiles

    OpenAIRE

    Sei-Ichi Denda; Tadashi Takahashi; Akihiro Sawamura

    1981-01-01

    In the course of the development of hybrid voltage regulators for automobile use, increasing the reverse blocking voltage with decreasing of saturation voltage for output power darlington transistors, the capability of monolithic IC chip against surge pulses generated in cars, and an improvement of the pattern design of thick film in order to withstand temperature cycling, have been important subjects. Power darlingtons have more than 150 V of reverse voltage as well as large secondary breakd...

  18. Regulation Mechanisms of Stomatal Oscillation

    Institute of Scientific and Technical Information of China (English)

    Hui-Min YANG; Jian-Hua ZHANG; Xiao-Yan ZHANG

    2005-01-01

    Stomata function as the gates between the plant and the atmospheric environment. Stomatal movement, including stomatal opening and closing, controls CO2 absorption as the raw material for photosynthesis and water loss through transpiration. How to reduce water loss and maintain enough CO2 absorption has been an interesting research topic for some time. Simple stomatal opening may elevate CO2 absorption,but, in the meantime, promote the water loss, whereas simple closing of stomatal pores may reduce both water loss and CO2 absorption, resulting in impairment of plant photosynthesis. Both processes are not economical to the plant. As a special rhythmic stomatal movement that usually occurs at smaller stomatal apertures, stomatal oscillation can keep CO2 absorption at a sufficient level and reduce water loss at the same time, suggesting a potential improvement in water use efficiency. Stomatal oscillation is usually found after a sudden change in one environmental factor in relatively constant environments. Many environmental stimuli can induce stomatal oscillation. It appears that, at the physiological level, feedback controls are involved in stomatal oscillation. At the cellular level, possibly two different patterns exist: (i) a quicker responsive pattern; and (ii) a slower response. Both involve water potential changes and water channel regulation, but the mechanisms of regulation of the two patterns are different. Some evidence suggests that the regulation of water channels may play a vital and primary role in stomatal oscillation. The present review summarizes studies on stomatal oscillation and concludes with some discussion regarding the mechanisms of regulation of stomatal oscillation.

  19. On self regulation and laughter

    DEFF Research Database (Denmark)

    Buhl, Mie

    and facilitating learning processes for the student or conducting research projects. Information technology exposes the teacher's and the researcher's performative dimensions: how teachers and researchers choose their acts in certain situations, and how that demands an intensified reflexivity.  It is...... that video streaming increases self regulation and laughter. The discussions are based on empirical material in relation to both video streamed teaching sessions and online discussions....

  20. HISTONE METHYLATION REGULATES MEMORY FORMATION

    OpenAIRE

    Gupta, Swati; Kim, Se Y.; Artis, Sonja; Molfese, David L.; Schumacher, Armin; Sweatt, J. David; Paylor, Richard E.; Lubin, Farah D.

    2010-01-01

    It has been established that regulation of chromatin structure through post-translational modification of histone proteins, primarily histone H3 phosphorylation and acetylation, is an important early step in the induction of synaptic plasticity and formation of long-term memory. In this study, we investigated the contribution of another histone modification, histone methylation, to memory formation in the adult hippocampus. We found that tri-methylation of histone H3 at lysine 4 (H3K4), an ac...

  1. International comparison of taxi regulations

    OpenAIRE

    Sytze Rienstra, Peter Bakker, Johan Visser

    2015-01-01

    IntroductionIn 2014, research was conducted to evaluate the changes made in 2011 to the taxi regulations contained in the national Passenger Transport Act 2000. During the course of this research, Uber’s introduction in the taxi market emerged as an increasingly important focal point. In particular, UberPOP – a service connecting customers to private drivers (operating their own vehicles) via a smartphone app – generated much debate. It is in this context that the Directorate General Accessib...

  2. Hate crimes and normative regulation

    Directory of Open Access Journals (Sweden)

    Kovačević Milica

    2011-01-01

    Full Text Available This paper is primarily devoted to issues related to the normative regulation of hate crimes, with special reference to the regulations of the Republic of Serbia, which are indirectly related to this matter. This kind of crimes are characterized by prejudices that perpetrators have towards injured parties, as members of certain, mostly, minority groups, due to which many hate crimes could be also called crimes of prejudice. In comparative law there are two different basic directions when it comes to regulating hate crimes: separation of hate crimes in a separate category on the one hand, and punishment of perpetrators of criminal acts with the detriment of minority groups through the usual charges of a given criminal justice system, on the other. The author finds that, regardless of the formal response forms, real life suggests that hate crimes can be essentially suppressed only by promoting values such as equality, respect for diversity and tolerance, and by continuous education of public about the danger of hate crimes.

  3. Endocannabinoid Regulation of Neuroendocrine Systems.

    Science.gov (United States)

    Tasker, Jeffrey G; Chen, Chun; Fisher, Marc O; Fu, Xin; Rainville, Jennifer R; Weiss, Grant L

    2015-01-01

    The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus. Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems. Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function. Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C. The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964). PMID:26638767

  4. The mother as hidden regulator

    Directory of Open Access Journals (Sweden)

    Annie Panzer

    2003-09-01

    Full Text Available A human baby is born with a decidedly immature brain, and is absolutely dependent on an intense relationship with its mother (or primary caregiver for brain maturation. In the short term, maternal regulation contributes to a more joyful baby, while in the long term it leads to the internalisation and development of self-regulatory capabilities. The ability to regulate one’s own emotional states is based on the development of right orbitofrontal dominance of dual limbic circuits, i.e. the excitatory sympathetic ventral tegmental circuit, and the inhibitory parasympathetic lateral tegmental circuit. Thus the child will be able to calm down after nigh overwhelming emotions by activating the parasympathetic system, but also to bounce back after setbacks by activating the sympathetic system. The mother influences the parcellation of the two limbic systems and thus the permanent excitation-inhibition autonomic balance of its prefrontal regulatory system. Repeated unregulated emotional states in the practicing period from 12-18 months pave the way for various psychological and psychiatric disorders in adulthood. It is worrisome that many children pass through this critical time in nursery schools, where a shortage of adult staff may lead to the scenario where a child’s emotions are repeatedly not modulated, with dire consequences for the internalisation of its future self-regulating capabilities.

  5. ENERGY REGULATION IN YOUNG PEOPLE

    Directory of Open Access Journals (Sweden)

    Caroline J. Dodd

    2007-09-01

    Full Text Available Obesity in young people is now realised as a worldwide crisis of epidemic proportion. The aetiology of this disease suggests a disruption in regulation of energy at the population level, leading to a positive energy balance and excess adiposity. The relative contribution of food intake and physical inactivity remains to be elucidated. Treatment interventions have aimed to create a deficit in energy balance through manipulation of physical activity, behavioural components or, to a lesser extent, dietary modification. Whether such intervention is maintained in the long-term is as yet unclear, however it seems a combination of therapies is optimal. Mindful of a mismatch between energy intake and expenditure, recent work has begun to examine the acute relationship between physical activity and food intake in children. Initial findings suggest a short-term delay in compensation through energy intake for exercise- induced energy expenditure. The overarching study of energy regulation in children and adolescents is clearly multifaceted in nature and variables to be assessed or manipulated require careful consideration. The collection of paediatric physical activity, energy expenditure and food intake data is a time-consuming process, fraught with potential sources of error. Investigators should consider the validity and reliability of these and other issues, alongside the logistics of any proposed study. Despite these areas of concern, recent advances in the field should provide exciting opportunities for future research in paediatric energy regulation on a variety of levels

  6. Musical affect regulation in infancy.

    Science.gov (United States)

    Trehub, Sandra E; Ghazban, Niusha; Corbeil, Mariève

    2015-03-01

    Adolescents and adults commonly use music for various forms of affect regulation, including relaxation, revitalization, distraction, and elicitation of pleasant memories. Mothers throughout the world also sing to their infants, with affect regulation as the principal goal. To date, the study of maternal singing has focused largely on its acoustic features and its consequences for infant attention. We describe recent laboratory research that explores the consequences of singing for infant affect regulation. Such work reveals that listening to recordings of play songs can maintain 6- to 9-month-old infants in a relatively contented or neutral state considerably longer than recordings of infant-directed or adult-directed speech. When 10-month-old infants fuss or cry and are highly aroused, mothers' multimodal singing is more effective than maternal speech at inducing recovery from such distress. Moreover, play songs are more effective than lullabies at reducing arousal in Western infants. We explore the implications of these findings along with possible practical applications. PMID:25773634

  7. Negative regulators of cell proliferation

    Science.gov (United States)

    Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Cell proliferation is governed by the influence of both mitogens and inhibitors. Although cell contact has long been thought to play a fundamental role in cell cycling regulation, and negative regulators have long been suspected to exist, their isolation and purification has been complicated by a variety of technical difficulties. Nevertheless, over recent years an ever-expanding list of putative negative regulators have emerged. In many cases, their biological inhibitory activities are consistent with density-dependent growth inhibition. Most likely their interactions with mitogenic agents, at an intracellular level, are responsible for either mitotic arrest or continued cell cycling. A review of naturally occurring cell growth inhibitors is presented with an emphasis on those factors shown to be residents of the cell surface membrane. Particular attention is focused on a cell surface sialoglycopeptide, isolated from intact bovine cerebral cortex cells, which has been shown to inhibit the proliferation of an unusually wide range of target cells. The glycopeptide arrest cells obtained from diverse species, both fibroblasts and epithelial cells, and a broad variety of transformed cells. Signal transduction events and a limited spectrum of cells that are refractory to the sialoglycopeptide have provided insight into the molecular events mediated by this cell surface inhibitor.

  8. Detecting aquaporin function and regulation

    Science.gov (United States)

    Madeira, Ana; Moura, Teresa; Soveral, Graça

    2016-02-01

    Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostic and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery.

  9. NRC - regulator of nuclear safety

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-05-01

    The U.S. Nuclear Regulatory Commission (NRC) was formed in 1975 to regulate the various commercial and institutional uses of nuclear energy, including nuclear power plants. The agency succeeded the Atomic Energy Commission, which previously had responsibility for both developing and regulating nuclear activities. Federal research and development work for all energy sources, as well as nuclear weapons production, is now conducted by the U.S. Department of Energy. Under its responsibility to protect public health and safety, the NRC has three principal regulatory functions: (1) establish standards and regulations, (2) issue licenses for nuclear facilities and users of nuclear materials, and (3) inspect facilities and users of nuclear materials to ensure compliance with the requirements. These regulatory functions relate to both nuclear power plants and to other uses of nuclear materials - like nuclear medicine programs at hospitals, academic activities at educational institutions, research work, and such industrial applications as gauges and testing equipment. The NRC places a high priority on keeping the public informed of its work. The agency recognizes the interest of citizens in what it does through such activities as maintaining public document rooms across the country and holding public hearings, public meetings in local areas, and discussions with individuals and organizations.

  10. Optical regulation of cell chain

    Science.gov (United States)

    Liu, Xiaoshuai; Huang, Jianbin; Zhang, Yao; Li, Baojun

    2015-06-01

    Formation of cell chains is a straightforward and efficient method to study the cell interaction. By regulating the contact sequence and interaction distance, the influence of different extracellular cues on the cell interaction can be investigated. However, it faces great challenges in stable retaining and precise regulation of cell chain, especially in cell culture with relatively low cell concentration. Here we demonstrated an optical method to realize the precise regulation of cell chain, including removing or adding a single cell, adjusting interaction distance, and changing cell contact sequence. After injecting a 980-nm wavelength laser beam into a tapered optical fiber probe (FP), a cell chain of Escherichia colis (E. colis) is formed under the optical gradient force. By manipulating another FP close to the cell chain, a targeted E. coli cell can be trapped by the FP and removed from the chain. Further, the targeted cell can be added back to the chain at different positions to change the cell contact sequence. The experiments were interpreted by numerical simulations and the impact of cell sizes and shapes on this method was analyzed.

  11. NRC - regulator of nuclear safety

    International Nuclear Information System (INIS)

    The U.S. Nuclear Regulatory Commission (NRC) was formed in 1975 to regulate the various commercial and institutional uses of nuclear energy, including nuclear power plants. The agency succeeded the Atomic Energy Commission, which previously had responsibility for both developing and regulating nuclear activities. Federal research and development work for all energy sources, as well as nuclear weapons production, is now conducted by the U.S. Department of Energy. Under its responsibility to protect public health and safety, the NRC has three principal regulatory functions: (1) establish standards and regulations, (2) issue licenses for nuclear facilities and users of nuclear materials, and (3) inspect facilities and users of nuclear materials to ensure compliance with the requirements. These regulatory functions relate to both nuclear power plants and to other uses of nuclear materials - like nuclear medicine programs at hospitals, academic activities at educational institutions, research work, and such industrial applications as gauges and testing equipment. The NRC places a high priority on keeping the public informed of its work. The agency recognizes the interest of citizens in what it does through such activities as maintaining public document rooms across the country and holding public hearings, public meetings in local areas, and discussions with individuals and organizations

  12. Deregulation, a challenge for regulators

    International Nuclear Information System (INIS)

    Deregulation and competitiveness in the electricity market invites the plant owner/operator to reduce operating cost with a potential reduction in maintenance, degradation of investment in safety, reduction of operating staff and a downgrading in research and development. On the other side, deregulation and competitiveness brings the social and industrial benefit of reducing the electricity cost. Regulatory organisations have to watch that the safety level of the plant does not go beyond the established level, while recognising the benefits of the new situation; therefore they have the moral responsibility of regulating nuclear energy effectively and efficiently and in eliminating unnecessary regulatory burdens. Regulation has evolved with time and in accordance with the knowledge gained from research and the analysis of operating experience. The knowledge gained has made it possible to follow the path of other modern advanced technologies, where risk is quantified and the system approved when the risk becomes lower than an accepted level. The regulatory use of this advanced tool is being now developed by the most advanced regulatory organisations, under the name of risk informed regulation, where the reference level is the expected frequency of core damage. Deregulation and competitiveness will not change the basis of the already well established procedure to verify compliance. Nevertheless, the contents of Safety Analysis Reports and other regulatory documents, such as Technical Specifications for Operation, offer room for improvement in the sense of being more to the roots of the matter and becoming more efficient tools in the verification process. The contents of these documents have been evolving along the time and they have become unnecessary voluminous and rather burdensome. Much work has been done to improve the efficiency of regulatory inspections by concentrating on basic aspects. As a partial application of the already mentioned risk-informed regulation

  13. Septins guide microtubule protrusions induced by actin-depolymerizing toxins like Clostridium difficile transferase (CDT).

    Science.gov (United States)

    Nölke, Thilo; Schwan, Carsten; Lehmann, Friederike; Østevold, Kristine; Pertz, Olivier; Aktories, Klaus

    2016-07-12

    Hypervirulent Clostridium difficile strains, which are associated with increased morbidity and mortality, produce the actin-ADP ribosylating toxin Clostridium difficile transferase (CDT). CDT depolymerizes actin, causes formation of microtubule-based protrusions, and increases pathogen adherence. Here, we show that septins (SEPT) are essential for CDT-induced protrusion formation. SEPT2, -6, -7, and -9 accumulate at predetermined protrusion sites and form collar-like structures at the base of protrusions. The septin inhibitor forchlorfenuron or knockdown of septins inhibits protrusion formation. At protrusion sites, septins colocalize with the GTPase Cdc42 (cell division control protein 42) and its effector Borg (binder of Rho GTPases), which act as up-stream regulators of septin polymerization. Precipitation and surface plasmon resonance studies revealed high-affinity binding of septins to the microtubule plus-end tracking protein EB1, thereby guiding incoming microtubules. The data suggest that CDT usurps conserved regulatory principles involved in microtubule-membrane interaction, depending on septins, Cdc42, Borgs, and restructuring of the actin cytoskeleton. PMID:27339141

  14. Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization.

    Science.gov (United States)

    Ryan, Marnie A; Nattamai, Kalpana J; Xing, Ellen; Schleimer, David; Daria, Deidre; Sengupta, Amitava; Köhler, Anja; Liu, Wei; Gunzer, Matthias; Jansen, Michael; Ratner, Nancy; Le Cras, Timothy D; Waterstrat, Amanda; Van Zant, Gary; Cancelas, Jose A; Zheng, Yi; Geiger, Hartmut

    2010-10-01

    Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine granulocyte colony-stimulating factor (G-CSF) has become the preferred source of HSPCs for stem cell transplants. However, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of donors, precluding autologous transplantation in those donors or substantially delaying transplant recovery time. Consequently, new regimens are needed to increase the number of stem cells in peripheral blood upon mobilization. Using a forward genetic approach in mice, we mapped the gene encoding the epidermal growth factor receptor (Egfr) to a genetic region modifying G-CSF-mediated HSPC mobilization. Amounts of EGFR in HSPCs inversely correlated with the cells' ability to be mobilized by G-CSF, implying a negative role for EGFR signaling in mobilization. In combination with G-CSF treatment, genetic reduction of EGFR activity in HSPCs (in waved-2 mutant mice) or treatment with the EGFR inhibitor erlotinib increased mobilization. Increased mobilization due to suppression of EGFR activity correlated with reduced activity of cell division control protein-42 (Cdc42), and genetic Cdc42 deficiency in vivo also enhanced G-CSF-induced mobilization. Our findings reveal a previously unknown signaling pathway regulating stem cell mobilization and provide a new pharmacological approach for improving HSPC mobilization and thereby transplantation outcomes. PMID:20871610

  15. Silencing of directional migration in roundabout4 knockdown endothelial cells

    Directory of Open Access Journals (Sweden)

    Roberts David D

    2008-11-01

    Full Text Available Abstract Background Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we have investigated gene knockdown analysis of endothelial Robos, in particular roundabout 4 (robo4, the predominant Robo in endothelial cells using small interfering RNA technology in vitro. Results Robo1 and Robo4 knockdown cells display distinct activity in endothelial cell migration assay. The knockdown of robo4 abrogated the chemotactic response of endothelial cells to serum but enhanced a chemokinetic response to Slit2, while robo1 knockdown cells do not display chemotactic response to serum or VEGF. Robo4 knockdown endothelial cells unexpectedly show up regulation of Rho GTPases. Zebrafish Robo4 rescues both Rho GTPase homeostasis and serum reduced chemotaxis in robo4 knockdown cells. Robo1 and Robo4 interact and share molecules such as Slit2, Mena and Vilse, a Cdc42-GAP. In addition, this study mechanistically implicates IRSp53 in the signaling nexus between activated Cdc42 and Mena, both of which have previously been shown to be involved with Robo4 signaling in endothelial cells. Conclusion This study identifies specific components of the Robo signaling apparatus that work together to guide directional migration of endothelial cells.

  16. Regulated polyploidy in halophilic archaea.

    Directory of Open Access Journals (Sweden)

    Sebastian Breuert

    Full Text Available Polyploidy is common in higher eukaryotes, especially in plants, but it is generally assumed that most prokaryotes contain a single copy of a circular chromosome and are therefore monoploid. We have used two independent methods to determine the genome copy number in halophilic archaea, 1 cell lysis in agarose blocks and Southern blot analysis, and 2 Real-Time quantitative PCR. Fast growing H. salinarum cells contain on average about 25 copies of the chromosome in exponential phase, and their ploidy is downregulated to 15 copies in early stationary phase. The chromosome copy number is identical in cultures with a twofold lower growth rate, in contrast to the results reported for several other prokaryotic species. Of three additional replicons of H. salinarum, two have a low copy number that is not growth-phase regulated, while one replicon even shows a higher degree of growth phase-dependent regulation than the main replicon. The genome copy number of H. volcanii is similarly high during exponential phase (on average 18 copies/cell, and it is also downregulated (to 10 copies as the cells enter stationary phase. The variation of genome copy numbers in the population was addressed by fluorescence microscopy and by FACS analysis. These methods allowed us to verify the growth phase-dependent regulation of ploidy in H. salinarum, and they revealed that there is a wide variation in genome copy numbers in individual cells that is much larger in exponential than in stationary phase. Our results indicate that polyploidy might be more widespread in archaea (or even prokaryotes in general than previously assumed. Moreover, the presence of so many genome copies in a prokaryote raises questions about the evolutionary significance of this strategy.

  17. Future of Radiation Protection Regulations.

    Science.gov (United States)

    Doss, Mohan

    2016-03-01

    THERE IS considerable disagreement in the scientific community regarding the carcinogenicity of low-dose radiation (LDR), with publications supporting opposing points of view. However, major flaws have been identified in many of the publications claiming increased cancer risk from LDR. The data generally recognized as the most important for assessing radiation effects in humans, the atomic bomb survivor data, are often cited to raise LDR cancer concerns. However, these data no longer support the linear no-threshold (LNT) model after the 2012 update but are consistent with radiation hormesis. Thus, a resolution of the controversy regarding the carcinogenicity of LDR appears to be imminent, with the rejection of the LNT model and acceptance of radiation hormesis. Hence, for setting radiation protection regulations, an alternative approach to the present one based on the LNT model is needed. One approach would be to determine the threshold dose for the carcinogenic effect of radiation from existing data and establish regulations to ensure radiation doses are kept well below the threshold dose. This can be done by setting dose guidelines specifying safe levels of radiation doses, with the requirement that these safe levels, referred to as guidance levels, not be exceeded significantly. Using this approach, a dose guidance level of 10 cGy for acute radiation exposures and 10 cGy y for exposures over extended periods of time are recommended. The concept of keeping doses as low as reasonably achievable, known as ALARA, would no longer be required for low-level radiation exposures not expected to exceed the dose guidance levels significantly. These regulations would facilitate studies using LDR for prevention and treatment of diseases. Results from such studies would be helpful in refining dose guidance levels. The dose guidance levels would be the same for the public and radiation workers to ensure everyone's safety. PMID:26808881

  18. Regulation of radioactive waste management

    International Nuclear Information System (INIS)

    This bulletin contains information about activities of the Nuclear Regulatory Authority of the Slovak Republic (UJD). In this leaflet the regulation of radioactive waste management of the UJD are presented. Radioactive waste (RAW) is the gaseous, liquid or solid material that contains or is contaminated with radionuclides at concentrations or activities greater than clearance levels and for which no use is foreseen. The classification of radioactive waste on the basis of type and activity level is: - transition waste; - short lived low and intermediate level waste (LlLW-SL); - long lived low and intermediate level waste (LlLW-LL); - high level waste. Waste management (in accordance with Act 130/98 Coll.) involves collection, sorting, treatment, conditioning, transport and disposal of radioactive waste originated by nuclear facilities and conditioning, transport to repository and disposal of other radioactive waste (originated during medical, research and industrial use of radioactive sources). The final goal of radioactive waste management is RAW isolation using a system of engineered and natural barriers to protect population and environment. Nuclear Regulatory Authority of the Slovak Republic regulates radioactive waste management in accordance with Act 130/98 Coll. Inspectors regularly inspect and evaluate how the requirements for nuclear safety at nuclear facilities are fulfilled. On the basis of safety documentation evaluation, UJD issued permission for operation of four radioactive waste management facilities. Nuclear facility 'Technologies for treatment and conditioning contains bituminization plants and Bohunice conditioning centre with sorting, fragmentation, evaporation, incineration, supercompaction and cementation. Final product is waste package (Fibre reinforced container with solidified waste) acceptable for near surface repository in Mochovce. Republic repository in Mochovce is built for disposal of short lived low and intermediate level waste. Next

  19. Securities regulation and implicit penalties

    Institute of Scientific and Technical Information of China (English)

    Donghua; Chen; Yuyan; Guan; Gang; Zhao; Feifei; Wu

    2011-01-01

    The extant literature offers extensive support for the significant role played by institutions in financial markets,but implicit regulation and monitoring have yet to be examined.This study fills this void in the literature by employing unique Chinese datasets to explore the implicit regulation and penalties imposed by the Chinese government in regulating the initial public offering(IPO) market.Of particular interest are the economic consequences of underwriting IPO deals for client firms that violate regulatory rules in China’s capital market.We provide evidence to show that the associated underwriters’ reputations are impaired and their market share declines.We further explore whether such negative consequences result from a market disciplinary mechanism or a penalty imposed by the government.To analyze the possibility of a market disciplinary mechanism at work,we investigate(1) the market reaction to other client firms whose IPO deals were underwritten by underwriters associated with a violation at the time the violation was publicly disclosed and(2) the under-pricing of IPO deals undertaken by these underwriters after such disclosure.To analyze whether the government imposes an implicit penalty,we examine the application processing time for future IPO deals underwritten by the associated underwriters and find it to be significantly longer than for IPO deals underwritten by other underwriters.Overall,there is little evidence to suggest that the market penalizes underwriters for the rule-violating behavior of their client firms in China.Instead,the Chinese government implicitly penalizes them by imposing more stringent criteria on and lengthening the processing time of the IPO deals they subsequently underwrite.

  20. 48 CFR Appendix - Federal Acquisition Regulation (FAR) Index

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Federal Acquisition Regulation (FAR) Index Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT... (IFMS) Contract clause. FAR Index Federal Acquisition Regulation (FAR) Index Editorial Note:...

  1. Regulation on radioactive waste management

    International Nuclear Information System (INIS)

    A national calculator control system for the metropolitan radioactive waste banks was developed in 1999. The NNSA reviewed by the regulations the feasibility of some rectification projects for uranium ore decommissioning and conducted field inspections on waste treating systems and radioactive waste banks at the 821 plant. The NNSA realized in 1999 the calculator control for the disposal sites of low and medium radioactive waste. 3 routine inspections were organized on the reinforced concrete structures for disposal units and their pouring of concrete at waste disposal site and specific requirements were put forth

  2. Velenje - Mislinja cycle track regulation

    OpenAIRE

    Vidonja, Klemen

    2013-01-01

    In my graduation thesis, I am planning a cycle track from Velenje to Mislinja, where it will be connected to an existing bike track to Otiški vrh. The cycle track would be placed on a deserted railway route from Velenje to Dravograd. A short section of cycle track is already in use, but it has to be repared. I planned the rest of the cycle track and I regulated it in a turist – recreational manner, suitable for all types of riders. The cycle track is placed away from traffic, does not dema...

  3. Mathematical Models of Gene Regulation

    Science.gov (United States)

    Mackey, Michael C.

    2004-03-01

    This talk will focus on examples of mathematical models for the regulation of repressible operons (e.g. the tryptophan operon), inducible operons (e.g. the lactose operon), and the lysis/lysogeny switch in phage λ. These ``simple" gene regulatory elements can display characteristics experimentally of rapid response to perturbations and bistability, and biologically accurate mathematical models capture these aspects of the dynamics. The models, if realistic, are always nonlinear and contain significant time delays due to transcriptional and translational delays that pose substantial problems for the analysis of the possible ranges of dynamics.

  4. Power electronics converters and regulators

    CERN Document Server

    Dokić, Branko L

    2015-01-01

    This book is the result of the extensive experience the authors gained through their year-long occupation at the Faculty of Electrical Engineering at the University of Banja Luka. Starting at the fundamental basics of electrical engineering, the book guides the reader into this field and covers all the relevant types of converters and regulators. Understanding is enhanced by the given examples, exercises and solutions. Thus this book can be used as a textbook for students, for self-study or as a reference book for professionals.

  5. Regulation of Compound Leaf Development

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2013-12-01

    Full Text Available Leaf morphology is one of the most variable, yet inheritable, traits in the plant kingdom. How plants develop a variety of forms and shapes is a major biological question. Here, we discuss some recent progress in understanding the development of compound or dissected leaves in model species, such as tomato (Solanum lycopersicum, Cardamine hirsuta and Medicago truncatula, with an emphasis on recent discoveries in legumes. We also discuss progress in gene regulations and hormonal actions in compound leaf development. These studies facilitate our understanding of the underlying regulatory mechanisms and put forward a prospective in compound leaf studies.

  6. QB1 - Stochastic Gene Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Munsky, Brian [Los Alamos National Laboratory

    2012-07-23

    Summaries of this presentation are: (1) Stochastic fluctuations or 'noise' is present in the cell - Random motion and competition between reactants, Low copy, quantization of reactants, Upstream processes; (2) Fluctuations may be very important - Cell-to-cell variability, Cell fate decisions (switches), Signal amplification or damping, stochastic resonances; and (3) Some tools are available to mode these - Kinetic Monte Carlo simulations (SSA and variants), Moment approximation methods, Finite State Projection. We will see how modeling these reactions can tell us more about the underlying processes of gene regulation.

  7. Content delivery network and regulation

    Institute of Scientific and Technical Information of China (English)

    PENG Jiu-sheng; LIANG Xiong-jian

    2006-01-01

    First, this article provides an introduction to the content delivery network (CDN), which has wide prospects but is still in its early stages in China. Second, this article depicts the present situation and the developing characteristics of CDN in China. Elaborating on the above-mentioned two points, this article identifies the numerous problems that are encountered during the development of CDN, such as indistinct service positioning and the hidden troubles of information security.Finally, this article presents several countermeasures for handling the problems, such as opening the market widely,making a rational service positioning, strengthening the regulation on information security, and punishing illegal operations and unfair competition.

  8. Regulating natural gas pipeline efficiency

    International Nuclear Information System (INIS)

    Proponents of gas pipeline capacity assignment---sometimes referred to as capacity brokering---would like a policy that would allow holders of gas pipeline capacity contact, usually firm transportation, to resell that capacity for short periods of time when it is not needed. In this paper the authors review the current U.S. policy towards capacity assignment in the context of FERC regulation of interstate pipelines and compare the U.S. debate with Canada's approach. The authors offer a modest proposal to institute a capacity assignment program experiment

  9. Regulating renewable resources under uncertainty

    DEFF Research Database (Denmark)

    Hansen, Lars Gårn

    Renewable natural resources (like water, fish and wildlife stocks, forests and grazing lands) are critical for the livelihood of millions of people and understanding how they can be managed efficiently is an important economic problem. I show how regulator uncertainty about different economic and......) that a pro-quota result under uncertainty about prices and marginal costs is unlikely, requiring that the resource growth function is highly concave locally around the optimum and, 3) that quotas are always preferred if uncertainly about underlying structural economic parameters dominates. These...

  10. The Cost of Railroad Regulation

    DEFF Research Database (Denmark)

    Federico, Giovanni; Sharp, Paul R.

    We investigate the costs of transportation regulation using the example of agricultural markets in the United States. Using a large database of prices by state of agricultural commodities, we find that the coefficient of variation (as a measure of market integration between states) falls for many...... commodities until the First World War. We demonstrate that this reflected changes in transportation costs which in turn in the long run depended on productivity growth in railroads. 1920 marked a change in this relationship, however, and between the First and Second World Wars we find considerable...

  11. Cell swelling and volume regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay

    1992-01-01

    The extracellular space in the brain is typically 20% of the tissue volume and is reduced to at least half its size under conditions of neural insult. Whether there is a minimum size to the extracellular space was discussed. A general model for cell volume regulation was presented, followed by a...... discussion on how many of the generally involved mechanisms are identified in neural cells and (or) in astrocytes. There seems to be clear evidence suggesting that parallel K+ and Cl- channels mediate regulatory volume decrease in primary cultures of astrocytes, and a stretch-activated cation channel has...

  12. Contract & agency labour: beyond self-regulation?

    OpenAIRE

    Cotton, Elizabeth

    2010-01-01

    A paper about the regulation of contract labour. Academic and legal aspects as well as case studies of global union federation work to organise and regulate contract labour in Thailand, Pakistan, Colombia, South Korea and at international level.

  13. 77 FR 11191 - Insurance Cost Information Regulation

    Science.gov (United States)

    2012-02-24

    ..., 58 FR 12545, NHTSA amended 49 CFR part 582, Insurance Cost Information Regulation, to require all... National Highway Traffic Safety Administration Insurance Cost Information Regulation AGENCY: National... insurance cost information booklet that all car dealers must make available to prospective...

  14. Tewaukon National Wildlife Refuge: Summer Fishing Regulation

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This memorandum summarizes the summer fishing regulation for Tewaukon National Wildlife Refuge as submitted to the Federal Register. This regulation defines areas...

  15. The financial regulations of the Agency

    International Nuclear Information System (INIS)

    On 8 June 1999, the Board of Governors adopted certain amendments to the IAEA Financial Regulations to take effect from 1 January 2002. A consolidated text of the Financial Regulations, as revised, will be issued in 2001

  16. Radiation Safety (Qualifications) Amendment Regulations 1984

    International Nuclear Information System (INIS)

    These Regulations amend the Radiation Safety (Qualifications) Regulations 1980 by establishing the fees to be paid for the radiation safety examination to be passed by persons engaged in activities involving radiation. (NEA)

  17. Institutions and Regulations in Innovation Systems

    DEFF Research Database (Denmark)

    Borrás, Susana; Edquist, Charles

    Institutions (including regulations) are constitutive elements of innovation systems, and therefore cornerstones of innovation policy. Focusing on (soft and hard) regulation, the paper identifies the most salient regulatory areas from the perspective of the innovation system. When asking about the...

  18. Regulation and electronic commerce in developing countries

    OpenAIRE

    Mansell, Robin

    2005-01-01

    This report is the result of dialogue and research focusing on the World Dialogue on Regulation (WDR) theme Stimulating Investment in Network Development: Roles for Regulators. The World Dialogue on Regulation for Network Economies (WDR) is an infoDev-funded project that is helping to facilitate infoDev’s objectives to broaden the reach and affordability of ICTs for all through its program of applied research, web-based dialogue, expert forum meetings with policymakers and regulators, and pub...

  19. Regulation of Motivation: Contextual and Social Aspects

    Science.gov (United States)

    Wolters, Christopher A.

    2011-01-01

    Background: Models of self-regulated learning have been used extensively as a way of understanding how students understand, monitor, and manage their own academic functioning. The regulation of motivation is a facet of self-regulated learning that describes students' efforts to control their own motivation or motivational processing. The…

  20. Self-Regulation and Mathematics Instruction

    Science.gov (United States)

    Montague, Marjorie

    2007-01-01

    The purpose of this article is to provide an overview of research-based interventions that incorporate self-regulation strategies to improve mathematics performance of students with learning disabilities (LD). Self-regulation is a metacognitive function essential to academic success. Students with LD are notoriously poor at self-regulation and…

  1. Good Practice Standards – a Regulation Tool

    DEFF Research Database (Denmark)

    Sørensen, Marie Jull

    2013-01-01

    The purpose of this article is to identify the considerations weighed in regulation with good practice standards. In this article, potential due process problems with regulation via legal standards are identified and compared to other considerations, which this regulation technique meets....

  2. Emotion Regulation and Depressive Symptoms in Preadolescence

    Science.gov (United States)

    Siener, Shannon; Kerns, Kathryn A.

    2012-01-01

    This study examined associations among several measures of emotion regulation, and their links to depressive symptoms, in a sample of children ages 10-12 years old (N = 87). Both temporal features of emotion regulation and regulation processes involved in the evaluation, monitoring, and modification of emotion were assessed through parent and…

  3. Regulations Protect Right of Disabled to Employment

    Institute of Scientific and Technical Information of China (English)

    NING LILI

    2007-01-01

    @@ On February 14, 2007, the 169th Executive Meeting of the State Council, China's central government, adopted the Regulations on Employment of the Disabled (hereinafter referred to as the Regulations). The Regulations, which became effective on May 1,comes as an important guarantee for the right of the disabled to work.

  4. Nonlinear internal models for output regulation

    OpenAIRE

    Byrnes, C. I.; Isidori, A.

    2003-01-01

    In this paper we show how nonlinear internal models can be effectively used in the design of output regulators for nonlinear systems. This result provides a significant enhancement of the non-equilibrium theory for output regulation, which we have presented in the recent paper entitled "Limit Sets, Zero Dynamics, and Internal Models in the Problem of Nonlinear Output Regulation".

  5. No. 434 - Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    This Regulation, made under the Radiation Control Act 1990, replaces the Radioactive Substances Regulation 1959, repealed by the 1990 Act. It deals with licensing of the use of radioactive substances and radiation apparatus, regulates their use, disposal and transport. It also provides for radiation monitoring and emergency planning. (NEA)

  6. Regulated trafficking of the CFTR chloride channel

    NARCIS (Netherlands)

    Braakman, L.J.; Kleizen, B.; Jonge, H.R. de

    2000-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR), the ABC transporter encoded by the cystic fibrosis gene, is localized in the apical membrane of epithelial cells where it functions as a cyclic AMP-regulated chloride channel and as a regulator of other ion channels and transporters. Wh

  7. [Consideration of Mobile Medical Device Regulation].

    Science.gov (United States)

    Peng, Liang; Yang, Pengfei; He, Weigang

    2015-07-01

    The regulation of mobile medical devices is one of the hot topics in the industry now. The definition, regulation scope and requirements, potential risks of mobile medical devices were analyzed and discussed based on mobile computing techniques and the FDA guidance of mobile medical applications. The regulation work of mobile medical devices in China needs to adopt the risk-based method. PMID:26665948

  8. 76 FR 62630 - Information Security Regulations

    Science.gov (United States)

    2011-10-11

    ... 32 CFR Part 1902 Information Security Regulations AGENCY: Central Intelligence Agency. ACTION: Final rule. SUMMARY: The Central Intelligence agency is removing certain information security regulations... Information security regulations. PART 1902 Sec. 1902.13 0 Accordingly, under the authority of Executive...

  9. The financial regulations of the Agency

    International Nuclear Information System (INIS)

    On 14 September 1994, the Board of Governors approved revised Financial Regulations of the Agency, with implementation of these Regulations beginning 1 January 1995. The Financial Regulations, as revised, are reproduced in this document for the information of all Member States

  10. Strategic regulation of gas transport

    International Nuclear Information System (INIS)

    The basis of the article has been the steadily increasing focus particularly from EU, on increased competition in the natural gas markets. This could influence the profit distribution between the gas producing and consuming counties which is an important problem situation for Norway as a gas producer. The gas market value chain consist of three parts (production, transport and distribution). How the countries may use strategic regulation of the transport tariff for the transport and distribution systems in order to move as much as possible of the total profit to the part of the value chain in control is studied. The focus has been on how increased competition influences the incentives of the authorities through low or high transport tariff and to what extent increased competition influences the welfare level in the producer and consumer counties when strategic regulations of the transport occur. The analysis is based on a theoretical model developed in 2005. Some central mechanisms related to the natural gas market are mapped and Norway may counteract some negative effects of liberalisation of the European gas market through strategic adaptation of the transport tariff to the Norwegian gas transport systems

  11. Brainstem Circuits Regulating Gastric Function

    Science.gov (United States)

    Travagli, R. Alberto; Hermann, Gerlinda E.; Browning, Kirsteen N.; Rogers, Richard C.

    2011-01-01

    Brainstem parasympathetic circuits that modulate digestive functions of the stomach are comprised of afferent vagal fibers, neurons of the nucleus tractus solitarius (NTS), and the efferent fibers originating in the dorsal motor nucleus of the vagus (DMV). A large body of evidence has shown that neuronal communications between the NTS and the DMV are plastic and are regulated by the presence of a variety of neurotransmitters and circulating hormones as well as the presence, or absence, of afferent input to the NTS. These data suggest that descending central nervous system inputs as well as hormonal and afferent feedback resulting from the digestive process can powerfully regulate vago-vagal reflex sensitivity. This paper first reviews the essential “static” organization and function of vago-vagal gastric control neurocircuitry. We then present data on the opioidergic modulation of NTS connections with the DMV as an example of the “gating” of these reflexes, i.e., how neurotransmitters, hormones, and vagal afferent traffic can make an otherwise static autonomic reflex highly plastic. PMID:16460274

  12. VOLTAGE REGULATORS OF SYNCHRONOUS GENERATORS

    Directory of Open Access Journals (Sweden)

    Grigorash O. V.

    2015-06-01

    Full Text Available Synchronous generators are the primary source of electrical power autonomous electrosupply systems, including backup systems. They are also used in a structure of rotating electricity converters and are widely used in renewable energy as part of wind power plants of small, mini and micro hydroelectric plants. Increasing the speed and the accuracy of the system of the voltage regulation of synchronous generators is possible due to the development of combined systems containing more stabilizers. The article illustrates the functional schemes of circuit voltage stabilizers and frequency synchronous generators (with electromagnetic excitation and permanent magnet excitation and describes the features of their work, including two and three-aggregate rotating converters of electricity used in uninterruptible power supply systems. To improve the technical characteristics of the system of stabilization we have proposed functional solutions for stabilizers of synchronous generators made on the base of direct frequency converters and using a transformer with a rotating magnetic field. To improve the reliability of and to improve the operational characteristics of the autonomous independent sources of electricity we suggest creating the main functional blocks and the elements of the stabilization system in a modular way. The functional circuit solutions of voltage regulators of synchronous generators and the characteristics of their work considered in the article, are able to improve the efficiency of pre-design work in the development of new technical solutions for stabilizing the voltage and the frequency in synchronous generators of electrosupply autonomous systems

  13. Transcriptional regulation of tenascin genes.

    Science.gov (United States)

    Chiovaro, Francesca; Chiquet-Ehrismann, Ruth; Chiquet, Matthias

    2015-01-01

    Extracellular matrix proteins of the tenascin family resemble each other in their domain structure, and also share functions in modulating cell adhesion and cellular responses to growth factors. Despite these common features, the 4 vertebrate tenascins exhibit vastly different expression patterns. Tenascin-R is specific to the central nervous system. Tenascin-C is an "oncofetal" protein controlled by many stimuli (growth factors, cytokines, mechanical stress), but with restricted occurrence in space and time. In contrast, tenascin-X is a constituitive component of connective tissues, and its level is barely affected by external factors. Finally, the expression of tenascin-W is similar to that of tenascin-C but even more limited. In accordance with their highly regulated expression, the promoters of the tenascin-C and -W genes contain TATA boxes, whereas those of the other 2 tenascins do not. This article summarizes what is currently known about the complex transcriptional regulation of the 4 tenascin genes in development and disease. PMID:25793574

  14. NRC regulation of DOE facilities

    International Nuclear Information System (INIS)

    The US Department of Energy (DOE), its contractors, and the Nuclear Regulatory Commission (NRC) are in for major changes if the DOE follows through on its intentions announced December 20, 1996. The DOE is seeking legislation to establish the NRC as the regulatory agency with jurisdiction over nuclear health, safety, and security at a wide range of DOE facilities. At this stage, it appears that as many as 200 (though not all) DOE facilities would be affected. On March 28, 1997, the NRC officially endorsed taking over the responsibility for regulatory oversight of DOE nuclear facilities as the DOE had proposed, contingent upon adequate funding, staffing resources, and a clear delineation of NRC authority. This article first contrasts the ways in which the NRC and the DOE carry out their basic regulatory functions. Next, it describes the NRC's current authority over DOE facilities and the status of the DOE's initiative to expand that authority. Then, it discusses the basic changes and impacts that can be expected in the regulation of DOE facilities. The article next describes key lessons learned from the recent transition of the GDPs from DOE oversight to NRC regulation and the major regulatory issues that arose in that transition. Finally, some general strategies are suggested for resolving issues likely to arise as the NRC assumes regulatory authority over DOE facilities

  15. The undertow of de-regulation : re-regulation

    International Nuclear Information System (INIS)

    Alberta, Ontario and New Brunswick each initiated steps to deregulate their electric power industries in order to remain competitive with lower electricity rates in certain American states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity re regulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry and then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Technological advances were taking place in the electricity sector, improving the viability of small gas turbines and making cogeneration possible. In the 1990s, Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all three provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

  16. Price Regulation and the Cost of Capital

    OpenAIRE

    Fernando T. Camacho; Flavio M. Menezes

    2010-01-01

    This paper investigates how price regulation under moral hazard can affect a regulated firm’s cost of capital. We consider stylised versions of the two most typical regulatory frameworks that have been applied over the last decades by regulators: Price Cap and Cost of Service. We show that there is a trade-off between lower operational costs and a higher cost of capital under Price Cap regulation and higher operational costs and lower cost of capital under Cost of Service regulation. As a r...

  17. Nuclear energy regulation in Argentina

    International Nuclear Information System (INIS)

    The Nuclear Regulatory Authority was established as an autonomous body reporting to the Presidency of Argentina by Act known as the Nuclear Activity National Act, and is empowered to regulate and control the nuclear activity with regard to radiation and nuclear safety, physical protection and nuclear non-proliferation issues. This report details functions and competence of the regulatory body in order to preserve its own independent criterion regarding every aspect of radiological and nuclear safety, and the global strategy of the regulatory system, which are concentrated in the following basics aspects: issue of the corresponding standards; execution of regulatory inspections and audits to verify the compliance with granted licenses and authorisations; independent execution of analyses and studies for the licensing process of nuclear installations; development of technical and scientific aspects associated to radiological and nuclear safety; training of personnel involved in radiological and nuclear safety, either belonging to the Regulatory Body or those working in installations, which perform practices under control. The regulatory control activities are carried out with independence of technical opinions and decisions; administrative autarchy; legal capacity to act in the field of public and private rights, and qualified personnel. The regulatory system complies with the concept of safety culture and its development, and the commitment to nuclear power plants' safety is made clear in design or operation concepts giving priority to safety over economic rentability of the installations. The compliance with Maintenance Programs, In-service Inspection Programs and good operation practices are also part of the commitment. This paper describes the organisational structure of the regulatory body, its human resources, personnel qualification and training, and the necessary financial resources. The regulatory body issues and establishes the standards, which regulate and

  18. Emotion Regulation in Sexually Abused Preschoolers.

    Science.gov (United States)

    Langevin, Rachel; Cossette, Louise; Hébert, Martine

    2016-02-01

    Emotion regulation is closely related to mental health in children and adults. Low emotion regulation competencies have been found in school-aged sexually abused girls. The aim of the present study was to investigate emotion regulation competencies in sexually abused preschool girls and boys using a multi-informant approach. Emotion regulation was assessed in 62 sexually abused and 65 non-abused preschoolers using the Emotion Regulation Checklist and the MacArthur Story Stem Battery. Both parents and educators reported lower emotion regulation competencies in sexually abused preschoolers, especially boys, than in non-abused children. The narrative task completed by the children also revealed lower emotion regulation competencies in sexually abused boys. These findings could have an important impact on intervention programs offered to these at-risk children. PMID:25724803

  19. Transport regulations for radioactive materials in Japan

    International Nuclear Information System (INIS)

    The IAEA Regulations for the Safe Transport of Radioactive Materials are taken as a basis for our national regulations to secure the safe transport of radioactive materials in Japan. The requirements for packaging and packages that are used to transport radioactive materials are based on the IAEA Regulations. Furthermore, in addition to the IAEA Regulations, the relative international regulations such as the IMDG code of IMO etc. are reviewed by our national authorities and applied to the conveyance such as the transport vehicle/vessel etc. that is used for the shipment. The transport system such as a transport caravan in Japan is intended to provide even greater safety during transport. The future activities to be discussed in the IAEA are how to adopt the IAEA Regulations to Member States as soon as possible and to evaluate the safety margin of the IAEA Regulations to the assumed accidents. (author)

  20. Large-scale river regulation

    International Nuclear Information System (INIS)

    Recent concern over human impacts on the environment has tended to focus on climatic change, desertification, destruction of tropical rain forests, and pollution. Yet large-scale water projects such as dams, reservoirs, and inter-basin transfers are among the most dramatic and extensive ways in which our environment has been, and continues to be, transformed by human action. Water running to the sea is perceived as a lost resource, floods are viewed as major hazards, and wetlands are seen as wastelands. River regulation, involving the redistribution of water in time and space, is a key concept in socio-economic development. To achieve water and food security, to develop drylands, and to prevent desertification and drought are primary aims for many countries. A second key concept is ecological sustainability. Yet the ecology of rivers and their floodplains is dependent on the natural hydrological regime, and its related biochemical and geomorphological dynamics. (Author)

  1. Dynamics of bacterial gene regulation

    Science.gov (United States)

    Narang, Atul

    2009-03-01

    The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model.

  2. Maximum Power Point Regulator System

    Science.gov (United States)

    Simola, J.; Savela, K.; Stenberg, J.; Tonicello, F.

    2011-10-01

    The target of the study done under the ESA contract No.17830/04/NL/EC (GSTP4) for Maximum Power Point Regulator System (MPPRS) was to investigate, design and test a modular power system (a core PCU) fulfilling requirement for maximum power transfer even after a single failure in the Power System by utilising a power concept without any potential and credible single point failure. The studied MPPRS concept is of a modular construction, able to track the MPP individually on each SA sections, maintaining its functionality and full power capability after a loss of a complete MPPR module (by utilizingN+1module).Various add-on DCDC converter topology candidates were investigated and redundancy, failure mechanisms and protection aspects were studied

  3. Cyberspace regulation: cesurist and traditionalists

    Directory of Open Access Journals (Sweden)

    Lino Santos

    2015-05-01

    Full Text Available In the amazing Code and Other Laws of Cyberspace, Professor L. Lessig writes "that something fundamental has changed" with cyberspace with regard to the state's ability to enforce the law. On the one hand, the structure and characteristics of cyberspace pose some difficulties related to jurisdiction and the choice of applicable law. On the other, it raises questions about the very concept of sovereignty as we know it. This paper examines the arguments of those who advocate a regulation of cyberspace on the edges of state sovereignty or within a new concept of sovereignty and capacity to enforce the law, and the arguments of those who reject this exceptional treatment of cyberspace.

  4. Multiple pathways regulate shoot branching

    Directory of Open Access Journals (Sweden)

    Catherine eRameau

    2015-01-01

    Full Text Available Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TCP transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply.

  5. Regulating anxiety with extrasynaptic inhibition.

    Science.gov (United States)

    Botta, Paolo; Demmou, Lynda; Kasugai, Yu; Markovic, Milica; Xu, Chun; Fadok, Jonathan P; Lu, Tingjia; Poe, Michael M; Xu, Li; Cook, James M; Rudolph, Uwe; Sah, Pankaj; Ferraguti, Francesco; Lüthi, Andreas

    2015-10-01

    Aversive experiences can lead to complex behavioral adaptations including increased levels of anxiety and fear generalization. The neuronal mechanisms underlying such maladaptive behavioral changes, however, are poorly understood. Here, using a combination of behavioral, physiological and optogenetic approaches in mouse, we identify a specific subpopulation of central amygdala neurons expressing protein kinase C δ (PKCδ) as key elements of the neuronal circuitry controlling anxiety. Moreover, we show that aversive experiences induce anxiety and fear generalization by regulating the activity of PKCδ(+) neurons via extrasynaptic inhibition mediated by α5 subunit-containing GABAA receptors. Our findings reveal that the neuronal circuits that mediate fear and anxiety overlap at the level of defined subpopulations of central amygdala neurons and demonstrate that persistent changes in the excitability of a single cell type can orchestrate complex behavioral changes. PMID:26322928

  6. Lignification: Flexibility, Biosynthesis and Regulation.

    Science.gov (United States)

    Zhao, Qiao

    2016-08-01

    Lignin is a complex phenolic polymer that is deposited in the secondary cell wall of all vascular plants. The evolution of lignin is considered to be a critical event during vascular plant development, because lignin provides mechanical strength, rigidity, and hydrophobicity to secondary cell walls to allow plants to grow tall and transport water and nutrients over a long distance. In recent years, great research efforts have been made to genetically alter lignin biosynthesis to improve biomass degradability for the production of second-generation biofuels. This global focus on lignin research has significantly advanced our understanding of the lignification process. Based on these advances, here I provide an overview of lignin composition, the biosynthesis pathway and its regulation. PMID:27131502

  7. Drug impurities: problems and regulations.

    Science.gov (United States)

    Pifferi, G; Mannucci, A

    1999-11-01

    The matter of impurities is a frequently debated issue, mainly focused on the validation of the analytical methods and on the toxicology of potential impurities. In the first part of the review, the classification, the source and the chemical aspects of impurities are briefly considered according to the current international regulations. A special attention is given to the analytical control, in both qualitative and quantitative terms, of unexpected impurities arising from changes in the manufacturing process or by degradation. The thresholds for identification and qualification of impurities in new drug substances and in new drug products are examined together with the safety studies, when required. Finally, the acceptance limits for four classes of residual solvents are also reported. PMID:10765465

  8. Implementing CITES regulations for timber.

    Science.gov (United States)

    Blundell, Arthur G

    2007-03-01

    Foresters are currently confronted with a new challenge. For the first time a commonly traded timber species has been listed on the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). At the 12th Conference of the Parties in November 2002, countries voted 68 to 30 to place the premier timber species of Latin America, big-leaf mahogany (Swietenia macrophylla King [Meliaceae]), on CITES Appendix II. Under Appendix II regulations, trade in mahogany requires that exporting countries verify that each shipment was legally obtained and that its harvest was non-detrimental to the survival of the species. Unfortunately, implementation has been weak, in part because countries have yet to develop a common, pragmatic, cost-effective system to make the legal and non-detriment findings. This paper recommends what such a system might include. PMID:17489241

  9. Analog regulation of metabolic demand

    Directory of Open Access Journals (Sweden)

    Muskhelishvili Georgi

    2011-03-01

    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  10. Microbial Regulation in Gorgonian Corals

    Directory of Open Access Journals (Sweden)

    Laura D. Mydlarz

    2012-06-01

    Full Text Available Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists.

  11. Erratic Black Hole Regulates Itself

    Science.gov (United States)

    2009-03-01

    New results from NASA's Chandra X-ray Observatory have made a major advance in explaining how a special class of black holes may shut off the high-speed jets they produce. These results suggest that these black holes have a mechanism for regulating the rate at which they grow. Black holes come in many sizes: the supermassive ones, including those in quasars, which weigh in at millions to billions of times the mass of the Sun, and the much smaller stellar-mass black holes which have measured masses in the range of about 7 to 25 times the Sun's mass. Some stellar-mass black holes launch powerful jets of particles and radiation, like seen in quasars, and are called "micro-quasars". The new study looks at a famous micro-quasar in our own Galaxy, and regions close to its event horizon, or point of no return. This system, GRS 1915+105 (GRS 1915 for short), contains a black hole about 14 times the mass of the Sun that is feeding off material from a nearby companion star. As the material swirls toward the black hole, an accretion disk forms. This system shows remarkably unpredictable and complicated variability ranging from timescales of seconds to months, including 14 different patterns of variation. These variations are caused by a poorly understood connection between the disk and the radio jet seen in GRS 1915. Chandra, with its spectrograph, has observed GRS 1915 eleven times since its launch in 1999. These studies reveal that the jet in GRS 1915 may be periodically choked off when a hot wind, seen in X-rays, is driven off the accretion disk around the black hole. The wind is believed to shut down the jet by depriving it of matter that would have otherwise fueled it. Conversely, once the wind dies down, the jet can re-emerge. "We think the jet and wind around this black hole are in a sort of tug of war," said Joseph Neilsen, Harvard graduate student and lead author of the paper appearing in the journal Nature. "Sometimes one is winning and then, for reasons we don

  12. Cap and trade offsets regulation - consultation paper

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    Due to increasing concerns about the environment, British Columbia has committed to reducing its 2007 greenhouse gas emissions levels by 33% in 2020 and 80% in 2050. To reach those objectives, emissions trading and offset regulations are being developed by the Climate Action Secretariat. The aim of this document is to present a first draft of the regulations to the various stakeholders, including First Nations and the general public, together with the proposed offset eligibility criteria and related process, and to get their feedback. This document is itself part of the 5-phase process of developing the regulations. Following the 45 days during which comments on the proposed regulation were sought, the climate action secretariat will complete legal drafting of the regulations, drawing on help from this stakeholder input, and the regulation will subsequently be implemented. An accompanying response form was attached to this consultation paper.

  13. Hormonal regulation of the hypothalamic melanocortin system

    Directory of Open Access Journals (Sweden)

    Jung Dae eKim

    2014-12-01

    Full Text Available Regulation of energy homeostasis is fundamental for life. In animal species and humans, the Central Nervous System (CNS plays a critical role in such regulation by integrating peripheral signals and modulating behavior and the activity of peripheral organs. A precise interplay between CNS and peripheral signals is necessary for the regulation of food intake and energy expenditure in the maintenance of energy balance. Within the CNS, the hypothalamus is a critical center for monitoring, processing and responding to peripheral signals, including hormones such as ghrelin, leptin and insulin. Once in the brain, peripheral signals regulate neuronal systems involved in the modulation of energy homeostasis. The main hypothalamic neuronal circuit in the regulation of energy metabolism is the melanocortin system. This review will give a summary of the most recent discoveries on the hormonal regulation of the hypothalamic melanocortin system in the control of energy homeostasis.

  14. Genome-wide Analysis of Gene Regulation

    DEFF Research Database (Denmark)

    Chen, Yun

    cells are capable of regulating their gene expression, so that each cell can only express a particular set of genes yielding limited numbers of proteins with specialized functions. Therefore a rigid control of differential gene expression is necessary for cellular diversity. On the other hand, aberrant...... gene regulation will disrupt the cell’s fundamental processes, which in turn can cause disease. Hence, understanding gene regulation is essential for deciphering the code of life. Along with the development of high throughput sequencing (HTS) technology and the subsequent large-scale data analysis......, genome-wide assays have increased our understanding of gene regulation significantly. This thesis describes the integration and analysis of HTS data across different important aspects of gene regulation. Gene expression can be regulated at different stages when the genetic information is passed from gene...

  15. The Recast Brussels I Regulation and Arbitration

    DEFF Research Database (Denmark)

    Hauberg Wilhelmsen, Louise

    2014-01-01

    Justice (ECJ) in the West Tankers case. The predominant interpretation of the existing exclusion of arbitration from the scope of the Regulation entails that a judgment disregarding or breaching an arbitration agreement will circulate in the European Union according to the rules of the Regulation. This......The revision of the Brussels I Regulation has come to an end. During the revision process the exclusion of arbitration from the scope of the Regulation has been much debated. This debate was not only ignited by the revision of the Regulation, but also by the decision of the European Court of...... entails an increased risk of parallel proceedings and conflicting decisions because the parties race to pursue both court litigation and arbitration proceedings. These implications have not been amended by the recast Regulation, which keeps the existing exclusion of arbitration from the scope of the...

  16. Ceramide-induced TCR up-regulation

    DEFF Research Database (Denmark)

    Menné, C; Lauritsen, Jens Peter Holst; Dietrich, J;

    2000-01-01

    kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected to...... pathway. Finally, we showed that TCR up-regulation probably plays a physiological role by increasing T cell responsiveness. Thus, by affecting the TCR recycling kinetics, T cells have the potential both to up- and down-regulate TCR expression and thereby adjust T cell responsiveness....... increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase...

  17. Exercise regulation of adipose tissue.

    Science.gov (United States)

    Stanford, Kristin I; Goodyear, Laurie J

    2016-01-01

    Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue. PMID:27386159

  18. [Cosmetic colorants. Toxicology and regulation].

    Science.gov (United States)

    Platzek, T; Krätke, R; Klein, G; Schulz, C

    2005-01-01

    Some recent publications raised concern over a possible link between hair dye use and the incidence of bladder tumours in a Californian population. The Scientific Committee for Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP) demanded the toxicological testing of all hair dyes used in Europe to exclude any risk. The EU commission initiated corresponding measures. Only safe hair dyes will be included on a positive list while all other hair dyes will be banned. The hair dye lawsone--the dyeing ingredient of henna--was evaluated by the SCCNFP as genotoxic but the BfR came to another conclusion. The regulation of both lawsone and henna remains an open question. Furthermore, some cosmetic colorants were critically discussed. The azo dyes CI 12150, CI 26100, CI 27290 and CI 20170 are allowed for use in cosmetics. On cleavage they form the carcinogenic aromatic amines o-anisidine, 4-aminoazobenzene and 2,4-xylidine, respectively. For three of these dyes the cleavage by human skin bacteria in vitro to the respective arylamine was shown experimentally. Further problems may arise from colorants used for tattoos and permanent makeup. These products up to now are not subject to legislation and there are no regulatory stipulations with respect to health safety and purity for colorants used for these purposes. PMID:15650909

  19. Proteinase activity regulation by glycosaminoglycans

    Directory of Open Access Journals (Sweden)

    Tersariol I.L.S.

    2002-01-01

    Full Text Available There are few reports concerning the biological role and the mechanisms of interaction between proteinases and carbohydrates other than those involved in clotting. It has been shown that the interplay of enzymes and glycosaminoglycans is able to modulate the activity of different proteases and also to affect their structures. From the large number of proteases belonging to the well-known protease families and also the variety of carbohydrates described as widely distributed, only few events have been analyzed more deeply. The term "family" is used to describe a group of proteases in which every member shows an evolutionary relationship to at least one other protease. This relationship may be evident throughout the entire sequence, or at least in that part of the sequence responsible for catalytic activity. The majority of proteases belong to the serine, cysteine, aspartic or metalloprotease families. By considering the existing limited proteolysis process, in addition to the initial idea that the proteinases participate only in digestive processes, it is possible to conclude that the function of the enzymes is strictly limited to the cleavage of intended substrates since the destruction of functional proteins would result in normal tissue damage. In addition, the location as well as the eventual regulation of protease activity promoted by glycosaminoglycans can play an essential role in the development of several physiopathological conditions.

  20. The Regulation of Energy Medicine

    Science.gov (United States)

    Kosovich, Judy; Esq

    This paper describes the laws and regulations that affect the practice of energy medicine. State law often has more impact on a health care practice than federal law, but federal law provides a common denominator among states. Device law is emphasized here because practitioners of energy medicine are more likely to use devices than drugs. For purposes of this paper, energy medicine is defined as practices that measure or benefit energy flow and overall energy in the body. This broad definition encompasses things as diverse as certain forms of exercise, measurement of meridian resistance, the use of electrical current or magnetic pulses to relieve pain, and the use of light, sound, scent, touch, position, or movement to stimulate the body's own electrical systems. What is of greatest importance in determining legal implications of a practice is whether there are any health-related claims. Two federal entities are pivotal. The Food and Drug Administration ("FDA") is authorized to protect health and safety and the Federal Trade Commission ("FTC") is authorized to protect consumers from false or misleading advertising. There are 5 things that FDA looks at: 1) intended use, 2) claims made in advertising and in labeling, 3) substantial equivalence to a predicate, 4) safety, and 5) effectiveness. A concern regarding any one of these can be the basis for denying clearance to market a device. The FTC looks at whether statements are true and substantiated and whether they might be misleading. The FTC often consults with the FDA on the interpretation of technical information.

  1. Regulation of Immunity by Butyrophilins.

    Science.gov (United States)

    Rhodes, David A; Reith, Walter; Trowsdale, John

    2016-05-20

    Butyrophilin molecules (commonly contracted to BTN), collectively take their name from the eponymous protein in cow's milk. They are considered to be members of the B7 family of costimulatory receptors, which includes B7.1 (CD80), B7.2 (CD86), and related molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276). These coreceptors modulate T cell responses upon antigen presentation by major histocompatibility complex and cognate αβ T cell receptor engagement. Molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein, and mouse Skint1 and Btnl2, all members of the butyrophilin family, show greater structural and functional diversity than the canonical B7 receptors. Some butyrophilins mediate complex interactions between antigen-presenting cells and conventional αβ T cells, and others regulate the immune responses of specific γδ T cell subsets by mechanisms that have characteristics of both innate and adaptive immunity. PMID:26772212

  2. Cytoskeletal regulation of dermal regeneration.

    Science.gov (United States)

    Strudwick, Xanthe L; Cowin, Allison J

    2012-01-01

    Wound healing results in the repair of injured tissues however fibrosis and scar formation are, more often than not the unfortunate consequence of this process. The ability of lower order vertebrates and invertebrates to regenerate limbs and tissues has been all but lost in mammals; however, there are some instances where glimpses of mammalian regenerative capacity do exist. Here we describe the unlocked potential that exists in mammals that may help us understand the process of regeneration post-injury and highlight the potential role of the actin cytoskeleton in this process. The precise function and regulation of the cytoskeleton is critical to the success of the healing process and its manipulation may therefore facilitate regenerative healing. The gelsolin family of actin remodelling proteins in particular has been shown to have important functions in wound healing and family member Flightless I (Flii) is involved in both regeneration and repair. Understanding the interactions between different cytoskeletal proteins and their dynamic control of processes including cellular adhesion, contraction and motility may assist the development of therapeutics that will stimulate regeneration rather than repair. PMID:24710556

  3. Good radiopharmacy practice and regulation

    International Nuclear Information System (INIS)

    Production, control, distribution and clinical application of radiopharmaceuticals have not been subject to the same regulations and legislation developed for conventional pharmaceutical products. Generally the production of radiopharmaceuticals have started up at national nuclear energy research centres, where the products have been regarded more as radioactive tracers than pharmaceutical products. Gradually pharmaceutical philosophy and requirements have been introduced in the field and necessary changes in legislation have been introduced. The registration process to obtain official market authorisation for a radiopharmaceutical have been introduced in most countries. This process of registration is constantly changing with regards to the amount and the type of documentation required by the health authorities. Correspondingly the general requirements for the systems applied in pharmacy for the production, control, quality assurance and medical application have also become an integral part of the field of radiopharmacy. Is the present situation generally satisfactory? The ever increasing demands leads to increasing costs and thereby higher prices on the products for the end users. Do the present requirements generally ensure that the radiopharmaceuticals applied are safe and effective for the patient? (author)

  4. Urotensin II in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    Fraser D Russell

    2008-08-01

    Full Text Available Fraser D RussellSchool of Health and Sport Sciences, Faculty of Science, Health and Education, University of the Sunshine Coast, Sippy Downs, Queensland, AustraliaAbstract: Cardiovascular function is modulated by neuronal transmitters, circulating hormones, and factors that are released locally from tissues. Urotensin II (UII is an 11 amino acid peptide that stimulates its’ obligatory G protein coupled urotensin II receptors (UT to modulate cardiovascular function in humans and in other animal species, and has been implicated in both vasculoprotective and vasculopathic effects. For example, tissue and circulating concentrations of UII have been reported to increase in some studies involving patients with atherosclerosis, heart failure, hypertension, preeclampsia, diabetes, renal disease and liver disease, raising the possibility that the UT receptor system is involved in the development and/or progression of these conditions. Consistent with this hypothesis, administration of UT receptor antagonists to animal models of cardiovascular disease have revealed improvements in cardiovascular remodelling and hemodynamics. However, recent studies have questioned this contributory role of UII in disease, and have instead postulated a protective effect on the cardiovascular system. For example, high concentrations of circulating UII correlated with improved clinical outcomes in patients with renal disease or myocardial infarction. The purpose of this review is to consider the regulation of the cardiovascular system by UII, giving consideration to methodologies for measurement of plasma concentrations, sites of synthesis and triggers for release.Keywords: urotensin II, cardiovascular disease, heart failure, hypertension

  5. Urotensin II in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    Fraser D Russell

    2008-09-01

    Full Text Available Fraser D RussellSchool of Health and Sport Sciences, Faculty of Science, Health and Education, University of the Sunshine Coast, Sippy Downs, Queensland, AustraliaAbstract: Cardiovascular function is modulated by neuronal transmitters, circulating hormones, and factors that are released locally from tissues. Urotensin II (UII is an 11 amino acid peptide that stimulates its’ obligatory G protein coupled urotensin II receptors (UT to modulate cardiovascular function in humans and in other animal species, and has been implicated in both vasculoprotective and vasculopathic effects. For example, tissue and circulating concentrations of UII have been reported to increase in some studies involving patients with atherosclerosis, heart failure, hypertension, preeclampsia, diabetes, renal disease and liver disease, raising the possibility that the UT receptor system is involved in the development and/or progression of these conditions. Consistent with this hypothesis, administration of UT receptor antagonists to animal models of cardiovascular disease have revealed improvements in cardiovascular remodelling and hemodynamics. However, recent studies have questioned this contributory role of UII in disease, and have instead postulated a protective effect on the cardiovascular system. For example, high concentrations of circulating UII correlated with improved clinical outcomes in patients with renal disease or myocardial infarction. The purpose of this review is to consider the regulation of the cardiovascular system by UII, giving consideration to methodologies for measurement of plasma concentrations, sites of synthesis and triggers for release.Keywords: urotensin II, cardiovascular disease, heart failure, hypertension

  6. The transcriptional regulation of pluripotency

    Institute of Scientific and Technical Information of China (English)

    Jia-Chi Yeo; Huck-Hui Ng

    2013-01-01

    The defining features of embryonic stem cells (ESCs) are their self-renewing and pluripotent capacities.Indeed,the ability to give rise into all cell types within the organism not only allows ESCs to function as an ideal in vitro tool to study embryonic development,but also offers great therapeutic potential within the field of regenerative medicine.However,it is also this same remarkable developmental plasticity that makes the efficient control of ESC differentiation into the desired cell type very difficult.Therefore,in order to harness ESCs for clinical applications,a detailed understanding of the molecular and cellular mechanisms controlling ESC pluripotency and lineage commitment is necessary.In this respect,through a variety of transcriptomic approaches,ESC pluripotency has been found to be regulated by a system of ESC-associated transcription factors; and the external signalling environment also acts as a key factor in modulating the ESC transcriptome.Here in this review,we summarize our current understanding of the transcriptional regulatory network in ESCs,discuss how the control of various signalling pathways could influence pluripotency,and provide a future outlook of ESC research.

  7. Regulation of microgeneration and microgrids

    International Nuclear Information System (INIS)

    The concept of microgrid (μGrid) has been emerging as a way to integrate microgeneration (μG) in low-voltage (LV) networks and simultaneously improve its potential benefits. Technical requirements to connect μgrids to LV networks have been studied in order to make this concept technologically feasible and safe to operate. However, the regulatory framework for economic integration of μG and μGrids on distribution systems, despite being crucial, is still an open issue. The main purpose of this paper is to contribute for the development of an appropriate economic regulation framework that removes the barriers to μG and μGrid development. To do so, the relevant costs and benefits resulting from the establishment of μG and μGrid are identified and a methodology for sharing those costs and benefits among the involved economic agents is presented. The only pre-requisite of such a methodology is the existence of a net benefit to all economic agents

  8. Asbestos products, hazards, and regulation.

    Science.gov (United States)

    Castleman, Barry

    2006-01-01

    Asbestos is present in the United States in a multitude of products used in past decades, and in some products that continue to be imported and domestically produced. We have limited information on the hazards posed by some of these individual products and no information at all on most of them. Legal discovery of corporate documents has shed some light on the use of asbestos in some products and exposures from asbestos in others, sometimes adding considerably to what was in the published literature. But liability concerns have motivated corporate efforts to curtail governmental public health guidance on long-recognized hazards to workers. Liability considerations have also evidently led, in the case of asbestos brake linings, to the support of publication in the scientific literature of review articles denying in the 21st century what had been widely accepted and established in health policy in the 20th century. This report is an effort to illustrate the suppression and emergence of scientific knowledge in a climate of regulation and liability. Examples discussed are vinyl-asbestos flooring, feminine hygiene products, automotive friction materials, and asbestos contamination of other minerals such as talc and vermiculite. Global efforts to deal with the hazards of continuing marketing of asbestos products are also discussed. PMID:16878394

  9. Regulation of pulpal blood flow

    International Nuclear Information System (INIS)

    The regulation of blood flow of the dental pulp was investigated in dogs and rats anesthetized with sodium pentobarbital. Pulpal blood flow was altered by variations of local and systemic hemodynamics. Macrocirculatory blood flow (ml/min/100 g) in the dental pulp was measured with both the 133Xe washout and the 15-microns radioisotope-labeled microsphere injection methods on the canine teeth of dogs, to provide a comparison of the two methods in the same tooth. Microcirculatory studies were conducted in the rat incisor tooth with microscopic determination of the vascular pattern, RBC velocity, and intravascular volumetric flow distribution. Pulpal resistance vessels have alpha- and beta-adrenergic receptors. Activation of alpha-receptors by intra-arterial injection of norepinephrine (NE) caused both a reduction in macrocirculatory Qp in dogs and decreases in arteriolar and venular diameters and intravascular volumetric flow (Qi) in rats. These responses were blocked by the alpha-antagonist PBZ. Activation of beta-receptors by intra-arterial injection of isoproterenal (ISO) caused a paradoxical reduction of Qp in dogs. In rats, ISO caused a transient increase in arteriolar Qi followed by a flow reduction; arteriolar dilation was accompanied by venular constriction. These macrocirculatory and microcirculatory responses to ISO were blocked by the alpha-antagonist propranolol

  10. Nutritional regulation of root development.

    Science.gov (United States)

    Ruiz Herrera, León Francisco; Shane, Michael W; López-Bucio, José

    2015-01-01

    Mineral nutrients such as nitrogen (N), phosphorus (P), and iron (Fe) are essential for plant growth, development, and reproduction. Adequate provision of nutrients via the root system impacts greatly on shoot biomass and plant productivity and is therefore of crucial importance for agriculture. Nutrients are taken up at the root surface in ionic form, which is mediated by specific transport proteins. Noteworthy, root tips are able to sense the local and internal concentrations of nutrients to adjust growth and developmental processes, and ultimately, to increase or decrease the exploratory capacity of the root system. Recently, important progress has been achieved in identifying the mechanisms of nutrient sensing in wild- and cultivated species, including Arabidopsis, bean, maize, rice, lupin as well as in members of the Proteaceae and Cyperaceae families, which develop highly sophisticated root clusters as adaptations to survive in soils with very low fertility. Major findings include identification of transporter proteins and transcription factors regulating nutrient sensing, miRNAs as mobile signals and peptides as repressors of lateral root development under heterogeneous nutrient supply. Understanding the roles played by N, P, and Fe in gene expression and biochemical characterization of proteins involved in root developmental responses to homogeneous or heterogeneous N and P sources has gained additional interest due to its potential for improving fertilizer acquisition efficiency in crops. PMID:25760021

  11. The Actin Binding Protein Adseverin Regulates Osteoclastogenesis

    OpenAIRE

    Hassanpour, Siavash; Jiang, Hongwei; Wang, Yongqiang; Kuiper, Johannes W. P.; Glogauer, Michael

    2014-01-01

    Adseverin (Ads), a member of the Gelsolin superfamily of actin binding proteins, regulates the actin cytoskeleton architecture by severing and capping existing filamentous actin (F-actin) strands and nucleating the assembly of new F-actin filaments. Ads has been implicated in cellular secretion, exocytosis and has also been shown to regulate chondrogenesis and megakaryoblastic leukemia cell differentiation. Here we report for the first time that Ads is involved in regulating osteoclastogenesi...

  12. Interconnection and incentive regulation in network industries

    OpenAIRE

    Iván Major; Károly M. Kiss

    2013-01-01

    The price regulation of network industries has changed tremendously all over the world recently. Theoretical contributions specifically advocate and telecommunications, energy and other market regulators in various parts of the world practice cost-based pricing for inter-firm network access services. Cost-based pricing is performed under the assumption that the regulator has perfect information regarding the costs of producing the services. We show that — under fairly general conditions — cos...

  13. Circuit Regulates Speed Of dc Motor

    Science.gov (United States)

    Weaver, Charles; Padden, Robin; Brown, Floyd A., Jr.

    1990-01-01

    Driving circuit regulates speed of small dc permanent-magnet motor in tape recorder. Two nested feedback loops maintain speed within 1 percent of constant value. Inner loop provides coarse regulation, while outer loop removes most of variation in speed that remains in the presence of regulation by the inner loop. Compares speed of motor with commanded speed and adjusts current supplied to motor accordingly.

  14. Medical devices regulations, standards and practices

    CERN Document Server

    Ramakrishna, Seeram; Wang, Charlene

    2015-01-01

    Medical Devices and Regulations: Standards and Practices will shed light on the importance of regulations and standards among all stakeholders, bioengineering designers, biomaterial scientists and researchers to enable development of future medical devices. Based on the authors' practical experience, this book provides a concise, practical guide on key issues and processes in developing new medical devices to meet international regulatory requirements and standards. Provides readers with a global perspective on medical device regulationsConcise and comprehensive information on how to desig

  15. Exploration on ecological regulation of the reservoirs

    Institute of Scientific and Technical Information of China (English)

    Cai Qihua

    2009-01-01

    Reservoir regulation process in the Yangtze River basin is mainly divided into two types of flood regulation and initiating benefit regulation. The present reservoir management system and operation mode are mainly for dealing with or coordinating of flood control and benefit initiation as well as benefit distribution among various beneficial functions. From the view point of river ecosystem protection, the current regulation mode has two kinds of problems: firstly, most of the reservoir regulation plans do not consider ecosystem protection at downstream of dams and needs of environment protection in reservoir areas; secondly, integrated regulation or management of water resources is ignored. It is very necessary to improve reservoir regulation mode, bearing problems faced by regulation of the Three Gorges reservoir and issues related to cascade development and regulation in Tuojiang and Minjiang River basins in mind. In accordance with the concept of scientific development, and the philosophy of "ensuring a healthy Yangtze River and promoting the har-mony between human and water", taking flood control, benefit initiation and eco-system as a whole, this paper put for-ward the basic consideration to improve reservoir regulation as follows : on the basis of requirements of ecosystem protec-tion at downstream of dams and needs of environment protection in reservoir areas, we should bring the functions of res-ervoir such as flood control and benefit initiation into full play, control the negative influence to the ecosystem at down-stream of dams and the environment in reservoir areas in an endurable scope, and restore the ecosystem and the environ-ment step by step. This paper put forward the relevant regulation process aiming at the idiographic problems such as pro-tection of ecosystem at downstream of dams and environment in reservoir areas, protection of aquatic wildlife species and fish species, regulation of sediment and protection of wetland.

  16. Insect Growth Regulators for Insect Pest Control*

    OpenAIRE

    TUNAZ, Hasan

    2004-01-01

    Insecticides with growth regulating properties (IGR) may adversely affect insects by regulating or inhibiting specific biochemical pathways or processes essential for insect growth and development. Some insects exposed to such compounds may die due to abnormal regulation of hormone-mediated cell or organ development. Other insects may die either from a prolonged exposure at the developmental stage to other mortality factors (susceptibility to natural enemies, environmental conditions etc) or ...

  17. Circadian Clock Proteins in Mood Regulation

    OpenAIRE

    Partonen, Timo

    2015-01-01

    Mood regulation is known to be affected by the change of seasons. Recent research findings have suggested that mood regulation may be influenced by the function of circadian clocks. In addition, the activity of brown adipocytes has been hypothesized to contribute to mood regulation. Here, the overarching link to mood disorders might be the circadian clock protein nuclear receptor subfamily 1, group D, member 1.

  18. World experience of state regulation of entrepreneurship

    OpenAIRE

    Bila Iryna S.; Salatiuk Nina M.

    2014-01-01

    The article analyses tendencies of state regulation of entrepreneurship in EU countries, USA and Japan and identifies state regulation of entrepreneurship as a system, which consists of certain elements, unity and interaction of which determine its efficiency and functionality. Analysis, systematisation and generalisation of experience of state regulation of entrepreneurship in these countries allow making a conclusion that the existing differences in the role of the state in economy are not ...

  19. Evaluation of Money Laundering Regulations in Ghana

    OpenAIRE

    Tontoh, Francis

    2008-01-01

    Purpose: The purpose of this thesis is to identify and appraise within the Ghanaian environment the level of regulations in combat of money laundering and terrorism financing, the extent of the regulation and the effectiveness of the regulations or laws. Method: Research methodology will be based on qualitative data collection and analysis approach which will consider the gathering of information personally by the researcher including interviews based on structured or semi-structures question...

  20. Evidence for Central Regulation of Glucose Metabolism*

    OpenAIRE

    Carey, Michelle; Kehlenbrink, Sylvia; Hawkins, Meredith

    2013-01-01

    Evidence for central regulation of glucose homeostasis is accumulating from both animal and human studies. Central nutrient and hormone sensing in the hypothalamus appears to coordinate regulation of whole body metabolism. Central signals activate ATP-sensitive potassium (KATP) channels, thereby down-regulating glucose production, likely through vagal efferent signals. Recent human studies are consistent with this hypothesis. The contributions of direct and central inputs to metabolic regulat...

  1. Hormonal regulation of the hypothalamic melanocortin system

    OpenAIRE

    Kim, Jung D.; Leyva, Stephanie; Diano, Sabrina

    2014-01-01

    Regulation of energy homeostasis is fundamental for life. In animal species and humans, the Central Nervous System (CNS) plays a critical role in such regulation by integrating peripheral signals and modulating behavior and the activity of peripheral organs. A precise interplay between CNS and peripheral signals is necessary for the regulation of food intake and energy expenditure in the maintenance of energy balance. Within the CNS, the hypothalamus is a critical center for monitoring, proce...

  2. Regulating Tobacco in the United States

    OpenAIRE

    Jonathan Gruber

    2002-01-01

    There has been a dramatic turn of events against the tobacco industry in the past few years, raising the question of the appropriate future path for smoking policy in the US. This paper discusses the theory and evidence on regulation of smoking. The author begins by reviewing the background on this industry. He then turns to a discussion of the motivations for regulating smoking. He argues that the available evidence suggests that we move from the traditional model, which ties regulation to c...

  3. Autokrine Regulation von Hepcidin in der Leber

    OpenAIRE

    Fritz, Sarah

    2012-01-01

    BACKGROUNDS AND AIMS: Hepcidin is an antimicrobial peptide and the central regulator of iron metabolism. Hepcidin is evidentially upregulated by iron overload as well as inflammation and downregulated by hypoxia or iron deficiency. However, the underlying mechanisms of hepcidin regulation are not completely understood yet. This study analyzed an autocrine regulation of hepcidin in human liver cells. METHODS: Human liver cells (HepG2, Hep3B) were stimulated with synthetic hepcidi...

  4. Circadian clock proteins in mood regulation

    Directory of Open Access Journals (Sweden)

    Timo ePartonen

    2015-01-01

    Full Text Available Mood regulation is known to be affected by the change of seasons. Recent research findings have suggested that mood regulation may be influenced by the function of circadian clocks. In addition, the activity of brown adipocytes has been hypothesized to contribute to mood regulation. Here, the overarching link to mood disorders might be the circadian clock protein NR1D1 (nuclear receptor subfamily 1, group D, member 1.

  5. The staff regulations of the Agency

    International Nuclear Information System (INIS)

    Following the first comprehensive review of the Provisional Staff Regulations conducted by the Secretariat, the Board of Governors approved on 12 June 2002 amendments to the Provisional Staff Regulations including the removal of the attribute 'provisional' from their title. The revised Staff Regulations of the Agency are set forth in this document for the information of all Members of the Agency. There is a subject index at the end of the document

  6. Regulation and Internet Use in Developing Countries

    OpenAIRE

    Wallsten, Scott

    2005-01-01

    Concerns about a worsening "digital divide" between rich and poor countries parallel the hope that information technology (IT) could increase economic growth in developing countries. Little research, however, has explored the role of public policies, and of regulation in particular, in IT growth. I use data from a unique new survey of telecommunications regulators and other sources to measure the effects of regulation on Internet development. Controlling for income and other factors that affe...

  7. Reflection amplifiers in self-regulated learning

    OpenAIRE

    Verpoorten, Dominique

    2012-01-01

    Verpoorten, D. (2012). Reflection amplifiers in self-regulated learning. Doctoral thesis. November, 9, 2012, Heerlen, The Netherlands: Open Universiteit (CELSTEC). Datawyse / Universitaire Pers Maastricht.

  8. Reflexive regulation of CSR to promote sustainability

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2011-01-01

    This article discusses Corporate Social Responsibility (CSR) from the perspective of governmental regulation as a measure to promote public policy interests through public-private regulation intended to influence firms’ self-regulation. Presenting a ‘government case’ for CSR, the connection between...... and the EU CSR Alliance. Focusing on human rights based in international law, it analyses the patterns of negotiation in the MSF and the background for the launch of the CSR Alliance. It shows that analysing public-private regulation of CSR from the perspective of reflexive law theory assists us in...

  9. 50 CFR 216.105 - Specific regulations.

    Science.gov (United States)

    2010-10-01

    ... MAMMALS General Regulations Governing Small Takes of Marine Mammals Incidental to Specified Activities... activity. (b) For allowed activities that may result in incidental takings of small numbers of...

  10. Legislation on and regulation of nuclear activities

    International Nuclear Information System (INIS)

    This work is a compilation of legislative texts and regulations published by the Atomic Energy Commission's Legal Affairs Department (CEA). It provides a comprehensive source of knowledge and information on nuclear energy law. Legislative texts published over the last forty years, are collected and analytically indexed. The publication covers both French regulations and regulations of international organisations such as the International Atomic Energy Agency and Euratom. It is divided into eight different chapters, dealing with regulations relevant to international and national institutions, nuclear installations, third party liability, protection of persons and the environment, etc. A chronological table of the texts of international and national laws is also included in this work. (NEA)

  11. Exporting licensing regulations affecting US geothermal firms

    Energy Technology Data Exchange (ETDEWEB)

    1988-08-01

    This document presents a brief introduction and overview of the Department of Commerce's Export Administration Regulations which might affect potential US geothermal goods exporters. It is intended to make US geothermal firms officials aware of the existence of such regulations and to provide them with references, contacts and phone numbers where they can obtain specific and detailed information and assistance. It must be stressed however, that the ultimate responsibility for complying with the above mentioned regulations lies with the exporter who must consult the complete version of the regulations.

  12. Scyl1 regulates Golgi morphology.

    Directory of Open Access Journals (Sweden)

    Jonathon L Burman

    Full Text Available BACKGROUND: Membrane trafficking is a defining feature of eukaryotic cells, and is essential for the maintenance of organelle homeostasis and identity. We previously identified Scy1-like 1 (Scyl1, a member of the Scy1-like family of catalytically inactive protein kinases, as a high-affinity binding partner of COPI coats. COPI-coated vesicles control Golgi to endoplasmic reticulum trafficking and we observed that disruption of Scyl1 function leads to a decrease in trafficking of the KDEL receptor via the COPI pathway. We reasoned that if Scyl1 plays a major role in COPI trafficking its disruption could influence Golgi homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: We performed Scyl1 knock down in cultured cells using previously established methods and observed an alteration in Golgi morphology. Both the surface area and volume of the Golgi is increased in Scyl1-depleted cells, but the continuity and polarity of the organelle is unperturbed. At the ultrastructural level we observe a decrease in the orderly structure of the Golgi with an increase in cisternal luminal width, while the number of Golgi cisternae remains unchanged. The golgin family of proteins forms a detergent resistant network that controls Golgi homeostasis. Disruption of this protein network by knock down of the golgin p115 disrupts the Golgi localization of Scyl1. Moreover, we find that Scyl1 interacts with 58K/formiminotransferase cyclodeaminase (FTCD, a protein that is tightly associated with the cis face of the Golgi. CONCLUSIONS/SIGNIFICANCE: Our results place Scyl1 at an interface between the golgin network and COPI trafficking and demonstrate that Scyl1 is required for the maintenance of Golgi morphology. Coupled with the observation from others that Scyl1 is the gene product responsible for the neurodegenerative mouse model mdf, our results additionally implicate the regulation of COPI trafficking and Golgi homeostasis in neurodegeneration.

  13. Microenvironmental regulation by fibrillin-1.

    Directory of Open Access Journals (Sweden)

    Gerhard Sengle

    2012-01-01

    Full Text Available Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes. A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated, even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently appreciated. Mutations in FBN1 are mainly responsible for the Marfan syndrome (MFS, recognized by its pleiotropic clinical features including tall stature and arachnodactyly, aortic dilatation and dissection, and ectopia lentis. Each of the many different mutations in FBN1 known to cause MFS must lead to similar clinical features through common mechanisms, proceeding principally through the activation of TGFβ signaling. Here we show that a novel FBN1 mutation in a family with Weill-Marchesani syndrome (WMS causes thick skin, short stature, and brachydactyly when replicated in mice. WMS mice confirm that this mutation does not cause MFS. The mutation deletes three domains in fibrillin-1, abolishing a binding site utilized by ADAMTSLIKE-2, -3, -6, and papilin. Our results place these ADAMTSLIKE proteins in a molecular pathway involving fibrillin-1 and ADAMTS-10. Investigations of microfibril ultrastructure in WMS humans and mice demonstrate that modulation of the fibrillin microfibril scaffold can influence local tissue microenvironments and link fibrillin-1 function to skin homeostasis and the regulation of dermal collagen production. Hence, pathogenetic mechanisms caused by dysregulated WMS microenvironments diverge from Marfan pathogenetic mechanisms, which lead to broad activation of TGFβ signaling in multiple tissues. We conclude that local tissue-specific microenvironments, affected in WMS, are maintained by a fibrillin-1 microfibril scaffold, modulated by ADAMTSLIKE proteins in concert with ADAMTS enzymes.

  14. Insulin secretion: mechanisms of regulation

    Directory of Open Access Journals (Sweden)

    Radosavljević Tatjana

    2004-01-01

    Full Text Available Regulation of insulin secretion Beta cells are unique endocrine cells. They respond positively, in terms of insulin secretion, not only to changes in the extracellular glucose concentration, but also to activators of the phospholipase C (cholecystokinin or acetylcholine, and to activators of adenylate cyclase (glucagon, glucagon-like peptide-1, or gastric inhibitory polypeptide. Major messengers which mediate glucose action for insulin release are Ca2%, adenosine triphosphate (ATP and diacylglycerol (DAG. Major pathways of insulin release stimulation There are four major pathways involved in stimulation of insulin release. The first pathway is KATP channel-dependent pathway in which increased blood glucose concentrations and increased b-cell metabolism result in a change in intracellular ATP/ADP ratio. This is a contributory factor in closure of ATP-dependent K% channels, depolarization of b-cell membrane, in increased voltage-dependent L-type Ca2%channel activity. Increased Ca2% influx results in increased intracellular Ca2% and stimulated insulin release. KATP channel-independent pathway augments Ca2%-stimulated insulun secretion of KATP channel-dependent pathway. Major potentiation of release results from hormonal and peptidergic activation of receptors linked to adenylyl cyclase. Adenylyl cyclase activity is stimulated by hormones such as vasoactive intestinal peptide (VIP, glucagon-like peptide-1 (GLP-1, and so on. These hormones, acting via G protein, stimulate adenylyl cyclase, thus causing a rise in cyclic adenosine monophosphate (cAMP and activation of protein kinase A (PKA. Increased activity of PKA results in potentiation of insulin secretion.

  15. Regulation and policy working group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The potential environmental impact of offshore platform disposal can be illustrated by both the numbers of platforms and the complexity of their abandonment options. Some 7,000 platforms are in place worldwide. In the US, approximately a quarter of the platforms are more than 25 years old and in sight of their end of service. In addition, 22,000 miles of pipeline are located on the Outer Continental Shelf (OCS) in the United States. There are more offshore platforms in the U.S. Gulf of Mexico than in any other single area in the world. It is estimated that between October 1995 and December 2000, approximately 665 of the nearly 3,800 existing structures will be removed. Couple this with the mammoth size, the vagaries of the ocean, and the levels of sometimes conflicting international and federal laws, and the magnitude of the challenge to protect the environment becomes clear. The Offshore International Newsletter (11/06/95) stated, {open_quotes}In three of the last four years, annual Gulf of Mexico platform removals have exceeded installations, a trend that will likely continue.{close_quotes} Between 100 and 150 platforms have been removed from the OCS each year for the past six or seven years. As increasing numbers of wells, pipelines, and platforms are decommissioned and disposed of, it is important that the relevant techniques, policies, and regulations be discussed and evaluated. The goal of this workshop is to facilitate and document this discussion in an open, objective, and inclusive way. Since U.S. practices and policies provide precedents for other countries, international participation is encouraged and anticipated.

  16. Harnessing science for environmental regulation

    International Nuclear Information System (INIS)

    An introductory chapter by Graham frames the issues to be discussed; then the following three chapters describe the formation and character of three organizations. These chapters are written by authors who have each had an active management role in the organization they are writing about: Terry F. Yosie, now at the American Petroleum Institute, who staffed the SAB (Science Advisory Board) while he was at EPA; Robert A. Neal, who headed CIIT (Chemical Industry Institute of Toxicology) before leaving for a position at Vanderbilt University; and Thomas P. Grumbly, former executive director of HEI (Health Effects Institute) now president of Clean Sites, Inc. While these chapters are well written and make a vital contribution to the overall development of the book's themes, the most valuable and enjoyable parts of the book are the succeeding five chapters, which present case studies dealing with EPA's regulatory efforts on unleaded gasoline, perchloroethylene, formaldehyde, nitrates in drinking water, and carbon monoxide. Each of these case studies, nominally historical accounts of how one or more of these (three) organizations participated in the regulatory controversy, offer insight into the broader issues of dealing with, and incorporating into regulations scientific information that has high uncertainty. One of the richest aspects of the five case studies is the extensive use of referenced interviews with identified participants from all aspects of the regulatory process. This material illuminates the motivation, emotions, and goals of the different players, helping the reader to understand their positions and other issues, such as why industry pursues, and EPA and the environmental movement appear to resist, good science; what underlies EPA's preferences for one regulatory option over another; and why scientists are histant to give yes-or-no answers in accord with the real time needs of the regulatory agency

  17. Radiation Safety (General) Regulations 1983 (Western Australia)

    International Nuclear Information System (INIS)

    The provisions of the Regulations cover, inter alia, the general precautions and requirements relating to radiation safety of the public and radiation workers and registration of irradiating apparatus or premises on which such apparatus is operated. In addition, the Regulations set forth requirements for the operation of such apparatus and for the premises involved. (NEA)

  18. Self-regulation through Goal Setting

    DEFF Research Database (Denmark)

    Koch, Alexander; Nafziger, Julia

    self-control problems. We show how goals permit self-regulation, but also that they are painful self-disciplining devices. Greater self-control problems therefore lead to stronger self-regulation through goals only up to a certain point. For severely present-biased preferences, the required goal for...

  19. Essays on incentives in regulation and innovation

    NARCIS (Netherlands)

    Jansen, J.A.

    2000-01-01

    The thesis contains three essays on incentives in regulation and innovation. The first essay analyzes a problem of optimal regulatory design. Key feature of the problem is that there exists asymmetric information between the regulator and the industry concerning the costs of producing complementary

  20. Independence of regulator authority of energy market

    International Nuclear Information System (INIS)

    From the 90's the European directives on energy markets have devoted increasing attention to the institution of national independent regulators. This paper aims at underlying the influence that the European law has on the design of national regulators and in particular on the importance and the meaning of their independence. Short reference will be made to the Italian experience as well.