WorldWideScience

Sample records for deregulated microtubule dynamics

  1. Microtubule dynamics: Caps, catastrophes, and coupled hydrolysis

    DEFF Research Database (Denmark)

    Flyvbjerg, H.; Holy, T.E.; Leibler, S.

    1996-01-01

    An effective theory is formulated for the dynamics of the guanosine triphosphate (GTP) cap believed to stabilize growing microtubules. The theory provides a ''coarse-grained'' description of the cap's dynamics. ''Microscopic'' details, such as the microtubule lattice structure and the fate of its...

  2. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

    Science.gov (United States)

    2012-07-01

    Std. Z39.18 Victoria Seewaldt, M.D. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation Duke University Durham...attomole- zeptomole range. Internal dilution curves insure a high-dynamic calibration range. DU -26 8L DU -26 6L DU -29 5R DU -22 9.2 L DU...3: Nanobiosensor technology is translated to test for pathway deregulation in RPFNA cytology obtained from 10 high-risk women with cytological

  3. The Role of Molecular Microtubule Motors and the Microtubule Cytoskeleton in Stress Granule Dynamics

    Directory of Open Access Journals (Sweden)

    Kristen M. Bartoli

    2011-01-01

    Full Text Available Stress granules (SGs are cytoplasmic foci that appear in cells exposed to stress-induced translational inhibition. SGs function as a triage center, where mRNAs are sorted for storage, degradation, and translation reinitiation. The underlying mechanisms of SGs dynamics are still being characterized, although many key players have been identified. The main components of SGs are stalled 48S preinitiation complexes. To date, many other proteins have also been found to localize in SGs and are hypothesized to function in SG dynamics. Most recently, the microtubule cytoskeleton and associated motor proteins have been demonstrated to function in SG dynamics. In this paper, we will discuss current literature examining the function of microtubules and the molecular microtubule motors in SG assembly, coalescence, movement, composition, organization, and disassembly.

  4. Melanophores for microtubule dynamics and motility assays.

    Science.gov (United States)

    Ikeda, Kazuho; Semenova, Irina; Zhapparova, Olga; Rodionov, Vladimir

    2010-01-01

    Microtubules (MTs) are cytoskeletal structures essential for cell division, locomotion, intracellular transport, and spatial organization of the cytoplasm. In most interphase cells, MTs are organized into a polarized radial array with minus-ends clustered at the centrosome and plus-ends extended to the cell periphery. This array directs transport of organelles driven by MT-based motor proteins that specifically move either to plus- or to minus-ends. Along with using MTs as tracks for cargo, motor proteins can organize MTs into a radial array in the absence of the centrosome. Transport of organelles and motor-dependent radial organization of MTs require MT dynamics, continuous addition and loss of tubulin subunits at minus- and plus-ends. A unique experimental system for studying the role of MT dynamics in these processes is the melanophore, which provides a useful tool for imaging of both dynamic MTs and moving membrane organelles. Melanophores are filled with pigment granules that are synchronously transported by motor proteins in response to hormonal stimuli. The flat shape of the cell and the radial organization of MTs facilitate imaging of dynamic MT plus-ends and monitoring of their interaction with membrane organelles. Microsurgically produced cytoplasmic fragments of melanophores are used to study the centrosome-independent rearrangement of MTs into a radial array. Here we describe the experimental approaches to study the role of MT dynamics in intracellular transport and centrosome-independent MT organization in melanophores. We focus on the preparation of cell cultures, microsurgery and microinjection, fluorescence labeling, and live imaging of MTs. 2010 Elsevier Inc. All rights reserved.

  5. Shaping the tracks : Regulation of microtubule dynamics by kinesins KIF21A and KIF21B

    NARCIS (Netherlands)

    van Riel, W.E.|info:eu-repo/dai/nl/338772634

    2016-01-01

    Control of microtubule dynamics is important for cell morphogenesis. Kinesins, motor proteins known to function in cargo transport, were recently also implicated in altering the microtubule network. Several kinesins are described to cause microtubule network reorganization or stabilization, either

  6. Nonlinear dynamics of C-terminal tails in cellular microtubules

    Science.gov (United States)

    Sekulic, Dalibor L.; Sataric, Bogdan M.; Zdravkovic, Slobodan; Bugay, Aleksandr N.; Sataric, Miljko V.

    2016-07-01

    The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano-electrical waves elicited in the rows of very flexible C-terminal tails which decorate the outer surface of each microtubule. The fact that C-terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule-associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink-waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.

  7. Nonlinear dynamics of C–terminal tails in cellular microtubules

    Energy Technology Data Exchange (ETDEWEB)

    Sekulic, Dalibor L., E-mail: dalsek@uns.ac.rs; Sataric, Bogdan M.; Sataric, Miljko V. [University of Novi Sad, Faculty of Technical Sciences, Novi Sad (Serbia); Zdravkovic, Slobodan [University of Belgrade, Institute of Nuclear Sciences Vinca, Belgrade (Serbia); Bugay, Aleksandr N. [Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Dubna (Russian Federation)

    2016-07-15

    The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano–electrical waves elicited in the rows of very flexible C–terminal tails which decorate the outer surface of each microtubule. The fact that C–terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule–associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink–waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.

  8. Nonlinear dynamics of C–terminal tails in cellular microtubules

    International Nuclear Information System (INIS)

    Sekulic, Dalibor L.; Sataric, Bogdan M.; Sataric, Miljko V.; Zdravkovic, Slobodan; Bugay, Aleksandr N.

    2016-01-01

    The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano–electrical waves elicited in the rows of very flexible C–terminal tails which decorate the outer surface of each microtubule. The fact that C–terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule–associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink–waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.

  9. Deficiency of RITA results in multiple mitotic defects by affecting microtubule dynamics.

    Science.gov (United States)

    Steinhäuser, K; Klöble, P; Kreis, N-N; Ritter, A; Friemel, A; Roth, S; Reichel, J M; Michaelis, J; Rieger, M A; Louwen, F; Oswald, F; Yuan, J

    2017-04-01

    Deregulation of mitotic microtubule (MT) dynamics results in defective spindle assembly and chromosome missegregation, leading further to chromosome instability, a hallmark of tumor cells. RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signaling pathway. Intriguingly, deregulated RITA is involved in primary hepatocellular carcinoma and other malignant entities. We were interested in the potential molecular mechanisms behind its involvement. We show here that RITA binds to tubulin and localizes to various mitotic MT structures. RITA coats MTs and affects their structures in vitro as well as in vivo. Tumor cell lines deficient of RITA display increased acetylated α-tubulin, enhanced MT stability and reduced MT dynamics, accompanied by multiple mitotic defects, including chromosome misalignment and segregation errors. Re-expression of wild-type RITA, but not RITA Δtub ineffectively binding to tubulin, restores the phenotypes, suggesting that the role of RITA in MT modulation is mediated via its interaction with tubulin. Mechanistically, RITA interacts with tubulin/histone deacetylase 6 (HDAC6) and its suppression decreases the binding of the deacetylase HDAC6 to tubulin/MTs. Furthermore, the mitotic defects and increased MT stability are also observed in RITA -/- mouse embryonic fibroblasts. RITA has thus a novel role in modulating MT dynamics and its deregulation results in erroneous chromosome segregation, one of the major reasons for chromosome instability in tumor cells.

  10. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

    2016-08-01

    High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

  11. Insurance brokers market dynamics in Poland before deregulation

    Directory of Open Access Journals (Sweden)

    Jarosław Krajewski

    2014-12-01

    Full Text Available The article focus on insurance broker profession in connection with second part of professions deregulations. It briefly presents modifications in polish law in this domain. Next part concerns the insurance brokers market dynamics analysis. The results shows permanent increase in brokers quantity in spite of existing regulations. Presented paper makes start point to following analysis.

  12. The engine of microtubule dynamics comes into focus.

    Science.gov (United States)

    Mitchison, T J

    2014-05-22

    In this issue, Alushin et al. report high-resolution structures of three states of the microtubule lattice: GTP-bound, which is stable to depolymerization; unstable GDP-bound; and stable Taxol and GDP-bound. By comparing these structures at near-atomic resolution, they are able to propose a detailed model for how GTP hydrolysis destabilizes the microtubule and thus powers dynamic instability and chromosome movement. Destabilization of cytoskeleton filaments by nucleotide hydrolysis is an important general principle in cell dynamics, and this work represents a major step forward on a problem with a long history. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Microtubules become more dynamic but not shorter during preprophase band formation: A possible "search-and-capture" mechanism for microtubule translocation

    NARCIS (Netherlands)

    Vos, J.W.; Dogterom, M.; Emons, A.M.C.

    2004-01-01

    The dynamic behavior of the microtubule cytoskeleton plays a crucial role in cellular organization, but the physical mechanisms underlying microtubule (re)organization in plant cells are poorly understood. We investigated microtubule dynamics in tobacco BY-2 suspension cells during interphase and

  14. Optical Tweezers-Based Measurements of Forces and Dynamics at Microtubule Ends.

    Science.gov (United States)

    Baclayon, Marian; Kalisch, Svenja-Marei; Hendel, Ed; Laan, Liedewij; Husson, Julien; Munteanu, E Laura; Dogterom, Marileen

    2017-01-01

    Microtubules are dynamic cytoskeletal polymers that polymerize and depolymerize while interacting with different proteins and structures within the cell. The highly regulated dynamic properties as well as the pushing and pulling forces generated by dynamic microtubule ends play important roles in processes such as in cell division. For instance, microtubule end-binding proteins are known to affect dramatically the dynamic properties of microtubules, and cortical dyneins are known to mediate pulling forces on microtubule ends. We discuss in this chapter our efforts to reconstitute these systems in vitro and mimic their interactions with structures within the cell using micro-fabricated barriers. Using an optical tweezers setup, we investigate the dynamics and forces of microtubules growing against functionalized barriers in the absence and presence of end-binding proteins and barrier-attached motor proteins. This setup allows high-speed as well as nanometer and piconewton resolution measurements on dynamic microtubules.

  15. EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

    Science.gov (United States)

    Wang, Yi-Long; Chen, Hui; Zhan, Yi-Qun; Yin, Rong-Hua; Li, Chang-Yan; Ge, Chang-Hui; Yu, Miao; Yang, Xiao-Ming

    2016-08-17

    EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

  16. Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles.

    Science.gov (United States)

    Prezel, Elea; Elie, Auréliane; Delaroche, Julie; Stoppin-Mellet, Virginie; Bosc, Christophe; Serre, Laurence; Fourest-Lieuvin, Anne; Andrieux, Annie; Vantard, Marylin; Arnal, Isabelle

    2018-01-15

    In neurons, microtubule networks alternate between single filaments and bundled arrays under the influence of effectors controlling their dynamics and organization. Tau is a microtubule bundler that stabilizes microtubules by stimulating growth and inhibiting shrinkage. The mechanisms by which tau organizes microtubule networks remain poorly understood. Here, we studied the self-organization of microtubules growing in the presence of tau isoforms and mutants. The results show that tau's ability to induce stable microtubule bundles requires two hexapeptides located in its microtubule-binding domain and is modulated by its projection domain. Site-specific pseudophosphorylation of tau promotes distinct microtubule organizations: stable single microtubules, stable bundles, or dynamic bundles. Disease-related tau mutations increase the formation of highly dynamic bundles. Finally, cryo-electron microscopy experiments indicate that tau and its variants similarly change the microtubule lattice structure by increasing both the protofilament number and lattice defects. Overall, our results uncover novel phosphodependent mechanisms governing tau's ability to trigger microtubule organization and reveal that disease-related modifications of tau promote specific microtubule organizations that may have a deleterious impact during neurodegeneration. © 2018 Prezel, Elie, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. Microtubules Nonlinear Models Dynamics Investigations through the exp(−Φ(ξ-Expansion Method Implementation

    Directory of Open Access Journals (Sweden)

    Nur Alam

    2016-02-01

    Full Text Available In this research article, we present exact solutions with parameters for two nonlinear model partial differential equations(PDEs describing microtubules, by implementing the exp(−Φ(ξ-Expansion Method. The considered models, describing highly nonlinear dynamics of microtubules, can be reduced to nonlinear ordinary differential equations. While the first PDE describes the longitudinal model of nonlinear dynamics of microtubules, the second one describes the nonlinear model of dynamics of radial dislocations in microtubules. The acquired solutions are then graphically presented, and their distinct properties are enumerated in respect to the corresponding dynamic behavior of the microtubules they model. Various patterns, including but not limited to regular, singular kink-like, as well as periodicity exhibiting ones, are detected. Being the method of choice herein, the exp(−Φ(ξ-Expansion Method not disappointing in the least, is found and declared highly efficient.

  18. NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents

    Science.gov (United States)

    Harkcom, William T.; Ghosh, Ananda K.; Sung, Matthew S.; Matov, Alexandre; Brown, Kevin D.; Giannakakou, Paraskevi; Jaffrey, Samie R.

    2014-01-01

    Nicotinamide adenine dinucleotide (NAD+) is an endogenous enzyme cofactor and cosubstrate that has effects on diverse cellular and physiologic processes, including reactive oxygen species generation, mitochondrial function, apoptosis, and axonal degeneration. A major goal is to identify the NAD+-regulated cellular pathways that may mediate these effects. Here we show that the dynamic assembly and disassembly of microtubules is markedly altered by NAD+. Furthermore, we show that the disassembly of microtubule polymers elicited by microtubule depolymerizing agents is blocked by increasing intracellular NAD+ levels. We find that these effects of NAD+ are mediated by the activation of the mitochondrial sirtuin sirtuin-3 (SIRT3). Overexpression of SIRT3 prevents microtubule disassembly and apoptosis elicited by antimicrotubule agents and knockdown of SIRT3 prevents the protective effects of NAD+ on microtubule polymers. Taken together, these data demonstrate that NAD+ and SIRT3 regulate microtubule polymerization and the efficacy of antimicrotubule agents. PMID:24889606

  19. Stable and dynamic microtubules coordinately shape the myosin activation zone during cytokinetic furrow formation

    Science.gov (United States)

    Foe, Victoria E.; von Dassow, George

    2008-01-01

    The cytokinetic furrow arises from spatial and temporal regulation of cortical contractility. To test the role microtubules play in furrow specification, we studied myosin II activation in echinoderm zygotes by assessing serine19-phosphorylated regulatory light chain (pRLC) localization after precisely timed drug treatments. Cortical pRLC was globally depressed before cytokinesis, then elevated only at the equator. We implicated cell cycle biochemistry (not microtubules) in pRLC depression, and differential microtubule stability in localizing the subsequent myosin activation. With no microtubules, pRLC accumulation occurred globally instead of equatorially, and loss of just dynamic microtubules increased equatorial pRLC recruitment. Nocodazole treatment revealed a population of stable astral microtubules that formed during anaphase; among these, those aimed toward the equator grew longer, and their tips coincided with cortical pRLC accumulation. Shrinking the mitotic apparatus with colchicine revealed pRLC suppression near dynamic microtubule arrays. We conclude that opposite effects of stable versus dynamic microtubules focuses myosin activation to the cell equator during cytokinesis. PMID:18955555

  20. Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability.

    Science.gov (United States)

    Deng, Xian; Fink, Gero; Bharat, Tanmay A M; He, Shaoda; Kureisaite-Ciziene, Danguole; Löwe, Jan

    2017-07-18

    Microtubules, the dynamic, yet stiff hollow tubes built from αβ-tubulin protein heterodimers, are thought to be present only in eukaryotic cells. Here, we report a 3.6-Å helical reconstruction electron cryomicroscopy structure of four-stranded mini microtubules formed by bacterial tubulin-like Prosthecobacter dejongeii BtubAB proteins. Despite their much smaller diameter, mini microtubules share many key structural features with eukaryotic microtubules, such as an M-loop, alternating subunits, and a seam that breaks overall helical symmetry. Using in vitro total internal reflection fluorescence microscopy, we show that bacterial mini microtubules treadmill and display dynamic instability, another hallmark of eukaryotic microtubules. The third protein in the btub gene cluster, BtubC, previously known as "bacterial kinesin light chain," binds along protofilaments every 8 nm, inhibits BtubAB mini microtubule catastrophe, and increases rescue. Our work reveals that some bacteria contain regulated and dynamic cytomotive microtubule systems that were once thought to be only useful in much larger and sophisticated eukaryotic cells.

  1. Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy

    NARCIS (Netherlands)

    Flex, Elisabetta; Niceta, Marcello; Cecchetti, Serena; Thiffault, Isabelle; Au, Margaret G.; Capuano, Alessandro; Piermarini, Emanuela; Ivanova, Anna A.; Francis, Joshua W.; Chillemi, Giovanni; Chandramouli, Balasubramanian; Carpentieri, Giovanna; Haaxma, Charlotte A.; Ciolfi, Andrea; Pizzi, Simone; Douglas, Ganka V.; Levine, Kara; Sferra, Antonella; Dentici, Maria Lisa; Pfundt, Rolph R.; Le Pichon, Jean-Baptiste; Farrow, Emily; Baas, Frank; Piemonte, Fiorella; Dallapiccola, Bruno; Graham, John M.; Saunders, Carol J.; Bertini, Enrico; Kahn, Richard A.; Koolen, David A.; Tartaglia, Marco

    2016-01-01

    Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause

  2. Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells.

    Science.gov (United States)

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

    2015-10-28

    Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies suggested that fisetin binds to β-tubulin with superior affinity compared to paclitaxel. Fisetin treatment of human prostate cancer cells resulted in robust up-regulation of microtubule associated proteins (MAP)-2 and -4. In addition, fisetin treated cells were enriched in α-tubulin acetylation, an indication of stabilization of microtubules. Fisetin significantly inhibited PCa cell proliferation, migration, and invasion. Nudc, a protein associated with microtubule motor dynein/dynactin complex that regulates microtubule dynamics, was inhibited with fisetin treatment. Further, fisetin treatment of a P-glycoprotein overexpressing multidrug-resistant cancer cell line NCI/ADR-RES inhibited the viability and colony formation. Our results offer in vitro proof-of-concept for fisetin as a microtubule targeting agent. We suggest that fisetin could be developed as an adjuvant for treatment of prostate and other cancer types. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Microtubule catastrophe and rescue.

    Science.gov (United States)

    Gardner, Melissa K; Zanic, Marija; Howard, Jonathon

    2013-02-01

    Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends of individual microtubules. The dynamic behavior at the end of an individual microtubule is termed 'dynamic instability'. This behavior manifests itself by periods of persistent microtubule growth interrupted by occasional switching to rapid shrinkage (called microtubule 'catastrophe'), and then by switching back from shrinkage to growth (called microtubule 'rescue'). In this review, we summarize recent findings which provide new insights into the mechanisms of microtubule catastrophe and rescue, and discuss the impact of these findings in regards to the role of microtubule dynamics inside of cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. An ELMO2-RhoG-ILK network modulates microtubule dynamics.

    Science.gov (United States)

    Jackson, Bradley C; Ivanova, Iordanka A; Dagnino, Lina

    2015-07-15

    ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin-dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3β, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca(2+)-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes. © 2015 Jackson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  5. Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast

    Science.gov (United States)

    Gergely, Zachary R.; Crapo, Ammon; Hough, Loren E.; McIntosh, J. Richard; Betterton, Meredith D.

    2016-01-01

    Kinesin-8 motor proteins destabilize microtubules. Their absence during cell division is associated with disorganized mitotic chromosome movements and chromosome loss. Despite recent work studying effects of kinesin-8s on microtubule dynamics, it remains unclear whether the kinesin-8 mitotic phenotypes are consequences of their effect on microtubule dynamics, their well-established motor activity, or additional, unknown functions. To better understand the role of kinesin-8 proteins in mitosis, we studied the effects of deletion of the fission yeast kinesin-8 proteins Klp5 and Klp6 on chromosome movements and spindle length dynamics. Aberrant microtubule-driven kinetochore pushing movements and tripolar mitotic spindles occurred in cells lacking Klp5 but not Klp6. Kinesin-8–deletion strains showed large fluctuations in metaphase spindle length, suggesting a disruption of spindle length stabilization. Comparison of our results from light microscopy with a mathematical model suggests that kinesin-8–induced effects on microtubule dynamics, kinetochore attachment stability, and sliding force in the spindle can explain the aberrant chromosome movements and spindle length fluctuations seen. PMID:27146110

  6. Microtubule dynamics. II. Kinetics of self-assembly

    DEFF Research Database (Denmark)

    Flyvbjerg, H.; Jobs, E.

    1997-01-01

    Inverse scattering theory describes the conditions necessary and sufficient to determine an unknown potential from known scattering data. No similar theory exists for when and how one may deduce the kinetics of an unknown chemical reaction from quantitative information about its final state and i...... to analyze the self-assembly of microtubules from tubulin are general, and many other reactions and processes may be studied as inverse problems with these methods when enough experimental data are available....

  7. Dictyoceratidan poisons: Defined mark on microtubule-tubulin dynamics.

    Science.gov (United States)

    Gnanambal K, Mary Elizabeth; Lakshmipathy, Shailaja Vommi

    2016-03-01

    Tubulin/microtubule assembly and disassembly is characterized as one of the chief processes during cell growth and division. Hence drugs those perturb these process are considered to be effective in killing fast multiplying cancer cells. There is a collection of natural compounds which disturb microtubule/tubulin dis/assemblage and there have been a lot of efforts concerted in the marine realm too, to surveying such killer molecules. Close to half the natural compounds shooting out from marine invertebrates are generally with no traceable definite mechanisms of action though may be tough anti-cancerous hits at nanogram levels, hence fatefully those discoveries conclude therein without a capacity of translation from laboratory to pharmacy. Astoundingly at least 50% of natural compounds which have definite mechanisms of action causing disorders in tubulin/microtubule kinetics have an isolation history from sponges belonging to the Phylum: Porifera. Poriferans have always been a wonder worker to treat cancers with a choice of, yet precise targets on cancerous tissues. There is a specific order: Dictyoceratida within this Phylum which has contributed to yielding at least 50% of effective compounds possessing this unique mechanism of action mentioned above. However, not much notice is driven to Dictyoceratidans alongside the order: Demospongiae thus dictating the need to know its select microtubule/tubulin irritants since the unearthing of avarol in the year 1974 till date. Hence this review selectively pinpoints all the compounds, noteworthy derivatives and analogs stemming from order: Dictyoceratida focusing on the past, present and future. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A computational framework for cortical microtubule dynamics in realistically shaped plant cells.

    Directory of Open Access Journals (Sweden)

    Bandan Chakrabortty

    2018-02-01

    Full Text Available Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

  9. A computational framework for cortical microtubule dynamics in realistically shaped plant cells

    KAUST Repository

    Chakrabortty, Bandan; Blilou, Ikram; Scheres, Ben; Mulder, Bela M.

    2018-01-01

    Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

  10. A computational framework for cortical microtubule dynamics in realistically shaped plant cells

    KAUST Repository

    Chakrabortty, Bandan

    2018-02-02

    Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

  11. TBCD links centriologenesis, spindle microtubule dynamics, and midbody abscission in human cells.

    Directory of Open Access Journals (Sweden)

    Mónica López Fanarraga

    2010-01-01

    Full Text Available Microtubule-organizing centers recruit alpha- and beta-tubulin polypeptides for microtubule nucleation. Tubulin synthesis is complex, requiring five specific cofactors, designated tubulin cofactors (TBCs A-E, which contribute to various aspects of microtubule dynamics in vivo. Here, we show that tubulin cofactor D (TBCD is concentrated at the centrosome and midbody, where it participates in centriologenesis, spindle organization, and cell abscission. TBCD exhibits a cell-cycle-specific pattern, localizing on the daughter centriole at G1 and on procentrioles by S, and disappearing from older centrioles at telophase as the protein is recruited to the midbody. Our data show that TBCD overexpression results in microtubule release from the centrosome and G1 arrest, whereas its depletion produces mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis. TBCD is recruited to the centriole replication site at the onset of the centrosome duplication cycle. A role in centriologenesis is further supported in differentiating ciliated cells, where TBCD is organized into "centriolar rosettes". These data suggest that TBCD participates in both canonical and de novo centriolar assembly pathways.

  12. KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

    Directory of Open Access Journals (Sweden)

    Lee B Smith

    Full Text Available Spermatogenesis is a complex process reliant upon interactions between germ cells (GC and supporting somatic cells. Testicular Sertoli cells (SC support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1. We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC from 15.5 days post-coitum (dpc and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

  13. Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy.

    Science.gov (United States)

    Flex, Elisabetta; Niceta, Marcello; Cecchetti, Serena; Thiffault, Isabelle; Au, Margaret G; Capuano, Alessandro; Piermarini, Emanuela; Ivanova, Anna A; Francis, Joshua W; Chillemi, Giovanni; Chandramouli, Balasubramanian; Carpentieri, Giovanna; Haaxma, Charlotte A; Ciolfi, Andrea; Pizzi, Simone; Douglas, Ganka V; Levine, Kara; Sferra, Antonella; Dentici, Maria Lisa; Pfundt, Rolph R; Le Pichon, Jean-Baptiste; Farrow, Emily; Baas, Frank; Piemonte, Fiorella; Dallapiccola, Bruno; Graham, John M; Saunders, Carol J; Bertini, Enrico; Kahn, Richard A; Koolen, David A; Tartaglia, Marco

    2016-10-06

    Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective β-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/β-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with

  14. Erucin, the major isothiocyanate in arugula (Eruca sativa, inhibits proliferation of MCF7 tumor cells by suppressing microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Olga Azarenko

    Full Text Available Consumption of cruciferous vegetables is associated with reduced risk of various types of cancer. Isothiocyanates including sulforaphane and erucin are believed to be responsible for this activity. Erucin [1-isothiocyanato-4-(methylthiobutane], which is metabolically and structurally related to sulforaphane, is present in large quantities in arugula (Eruca sativa, Mill., kohlrabi and Chinese cabbage. However, its cancer preventive mechanisms remain poorly understood. We found that erucin inhibits proliferation of MCF7 breast cancer cells (IC50 = 28 µM in parallel with cell cycle arrest at mitosis (IC50 = 13 µM and apoptosis, by a mechanism consistent with impairment of microtubule dynamics. Concentrations of 5-15 µM erucin suppressed the dynamic instability of microtubules during interphase in the cells. Most dynamic instability parameters were inhibited, including the rates and extents of growing and shortening, the switching frequencies between growing and shortening, and the overall dynamicity. Much higher erucin concentrations were required to reduce the microtubule polymer mass. In addition, erucin suppressed dynamic instability of microtubules reassembled from purified tubulin in similar fashion. The effects of erucin on microtubule dynamics, like those of sulforaphane, are similar qualitatively to those of much more powerful clinically-used microtubule-targeting anticancer drugs, including taxanes and the vinca alkaloids. The results suggest that suppression of microtubule dynamics by erucin and the resulting impairment of critically important microtubule-dependent cell functions such as mitosis, cell migration and microtubule-based transport may be important in its cancer preventive activities.

  15. Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Maki Takagishi

    2017-07-01

    Full Text Available Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a coordinated beating motion that drives directional cerebrospinal fluid (CSF flow and guides neuroblast migration. At the apical cortex of these multi-ciliated cells, asymmetric localization of planar cell polarity (PCP proteins is required for the planar polarization of microtubule dynamics, which coordinates cilia orientation. Daple is a disheveled-associating protein that controls the non-canonical Wnt signaling pathway and cell motility. Here, we show that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies required for the directional cerebrospinal fluid flow. These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells.

  16. Microtubule Catastrophe and Rescue

    OpenAIRE

    Gardner, Melissa K.; Zanic, Marija; Howard, Jonathon

    2012-01-01

    Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends...

  17. A dynamic approach for the optimal electricity dispatch in the deregulated market

    International Nuclear Information System (INIS)

    Carraretto, Cristian; Lazzaretto, Andrea

    2004-01-01

    The electricity market has been experiencing the deregulation process in many countries. Effective approaches to the management of single power plants or groups of plants are therefore becoming crucial for the competitiveness of energy utilities. A dynamic programming approach is presented in this paper for the optimal plant management in the new Italian deregulated market. A thorough description of the method is given in cases of free or fixed production over time (e.g. when the overall production is limited by bilateral contracts or cogeneration). Analysis of market characteristics, detailed thermodynamic models of plant operation and reliable price forecasts over the time period of interest are required. The suggested approach is useful for both long-term scheduling and planning daily offers in the market

  18. Plasma membrane factor XIIIA transglutaminase activity regulates osteoblast matrix secretion and deposition by affecting microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Hadil F Al-Jallad

    2011-01-01

    Full Text Available Transglutaminase activity, arising potentially from transglutaminase 2 (TG2 and Factor XIIIA (FXIIIA, has been linked to osteoblast differentiation where it is required for type I collagen and fibronectin matrix deposition. In this study we have used an irreversible TG-inhibitor to 'block -and-track' enzyme(s targeted during osteoblast differentiation. We show that the irreversible TG-inhibitor is highly potent in inhibiting osteoblast differentiation and mineralization and reduces secretion of both fibronectin and type I collagen and their release from the cell surface. Tracking of the dansyl probe by Western blotting and immunofluorescence microscopy demonstrated that the inhibitor targets plasma membrane-associated FXIIIA. TG2 appears not to contribute to crosslinking activity on the osteoblast surface. Inhibition of FXIIIA with NC9 resulted in defective secretory vesicle delivery to the plasma membrane which was attributable to a disorganized microtubule network and decreased microtubule association with the plasma membrane. NC9 inhibition of FXIIIA resulted in destabilization of microtubules as assessed by cellular Glu-tubulin levels. Furthermore, NC9 blocked modification of Glu-tubulin into 150 kDa high-molecular weight Glu-tubulin form which was specifically localized to the plasma membrane. FXIIIA enzyme and its crosslinking activity were colocalized with plasma membrane-associated tubulin, and thus, it appears that FXIIIA crosslinking activity is directed towards stabilizing the interaction of microtubules with the plasma membrane. Our work provides the first mechanistic cues as to how transglutaminase activity could affect protein secretion and matrix deposition in osteoblasts and suggests a novel function for plasma membrane FXIIIA in microtubule dynamics.

  19. Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma.

    Science.gov (United States)

    Landen, Jaren W; Lang, Roland; McMahon, Steve J; Rusan, Nasser M; Yvon, Anne-Marie; Adams, Ashley W; Sorcinelli, Mia D; Campbell, Ross; Bonaccorsi, Paola; Ansel, John C; Archer, David R; Wadsworth, Patricia; Armstrong, Cheryl A; Joshi, Harish C

    2002-07-15

    Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P microtubule dynamics, with no detected toxicity to the host. Consequently, noscapine could be a valuable chemotherapeutic agent, alone or in combination, for the treatment of advanced melanoma.

  20. ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics.

    Directory of Open Access Journals (Sweden)

    Michael D Stubenvoll

    2016-09-01

    Full Text Available Centrosomes are critical sites for orchestrating microtubule dynamics, and exhibit dynamic changes in size during the cell cycle. As cells progress to mitosis, centrosomes recruit more microtubules (MT to form mitotic bipolar spindles that ensure proper chromosome segregation. We report a new role for ATX-2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA-independent fashion. Depleting ATX-2 results in embryonic lethality and cytokinesis failure, and restores centrosome duplication to zyg-1 mutants. In this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with centrosome size. Centrosomes depleted of ATX-2 exhibit elevated levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin, increasing MT nucleating activity but impeding MT growth. We show that ATX-2 influences MT behavior through γ-Tubulin at the centrosome. Our data suggest that RNA-binding proteins play an active role in controlling MT dynamics and provide insight into the control of proper centrosome size and MT dynamics.

  1. Dynamic voltage stability constrained congestion management framework for deregulated electricity markets

    International Nuclear Information System (INIS)

    Amjady, Nima; Hakimi, Mahmood

    2012-01-01

    Highlights: ► A new congestion management method for electricity markets is proposed. ► The proposed method includes dynamic models of generators and loads. ► Dynamic voltage stability limits are properly modeled in the proposed method. ► The proposed method is compared with several other congestion management methods. ► It leads to a more robust power system with a lower congestion management cost. - Abstract: Congestion management is an important part of power system operation in today deregulated electricity markets. However, congestion management is traditionally performed based on static analysis tools, while these tools may not correctly capture dynamic voltage stability limits of a power system. In this paper, a new congestion management framework considering dynamic voltage stability boundary of power system is proposed. For this purpose, precise dynamic modeling of power system equipment, including generators and loads, is incorporated into the proposed congestion management framework. The proposed method alleviates congestion with a lower congestion management cost and more dynamic voltage stability margin, resulting in a more robust power system, compared with the previous congestion management methods. The validity of proposed congestion management framework is studied based on the New England 39-bus power system. The obtained results confirm the validity of the developed approach.

  2. Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

    OpenAIRE

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

    2015-01-01

    Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies sugges...

  3. An agent-based model contrasts opposite effects of dynamic and stable microtubules on cleavage furrow positioning.

    Science.gov (United States)

    Odell, Garrett M; Foe, Victoria E

    2008-11-03

    From experiments by Foe and von Dassow (Foe, V.E., and G. von Dassow. 2008. J. Cell Biol. 183:457-470) and others, we infer a molecular mechanism for positioning the cleavage furrow during cytokinesis. Computer simulations reveal how this mechanism depends on quantitative motor-behavior details and explore how robustly this mechanism succeeds across a range of cell sizes. The mechanism involves the MKLP1 (kinesin-6) component of centralspindlin binding to and walking along microtubules to stimulate cortical contractility where the centralspindlin complex concentrates. The majority of astral microtubules are dynamically unstable. They bind most MKLP1 and suppress cortical Rho/myosin II activation because the tips of unstable microtubules usually depolymerize before MKLP1s reach the cortex. A subset of astral microtubules stabilizes during anaphase, becoming effective rails along which MKLP1 can actually reach the cortex. Because stabilized microtubules aim statistically at the equatorial spindle midplane, that is where centralspindlin accumulates to stimulate furrow formation.

  4. An antitubulin agent BCFMT inhibits proliferation of cancer cells and induces cell death by inhibiting microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Ankit Rai

    Full Text Available Using cell based screening assay, we identified a novel anti-tubulin agent (Z-5-((5-(4-bromo-3-chlorophenylfuran-2-ylmethylene-2-thioxothiazolidin-4-one (BCFMT that inhibited proliferation of human cervical carcinoma (HeLa (IC(50, 7.2 ± 1.8 µM, human breast adenocarcinoma (MCF-7 (IC(50, 10.0 ± 0.5 µM, highly metastatic breast adenocarcinoma (MDA-MB-231 (IC(50, 6.0 ± 1 µM, cisplatin-resistant human ovarian carcinoma (A2780-cis (IC(50, 5.8 ± 0.3 µM and multi-drug resistant mouse mammary tumor (EMT6/AR1 (IC(50, 6.5 ± 1 µM cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 µM, BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably state by 135% and reduced the dynamicity (dimer exchange per unit time of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 ± 1.8 µM, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K(i of 5.2 ± 1.5 µM suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2 at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug

  5. The dynamic interplay of plasma membrane domains and cortical microtubules in secondary cell wall patterning

    Directory of Open Access Journals (Sweden)

    Yoshihisa eOda

    2013-12-01

    Full Text Available Patterning of the cellulosic cell wall underlies the shape and function of plant cells. The cortical microtubule array plays a central role in the regulation of cell wall patterns. However, the regulatory mechanisms by which secondary cell wall patterns are established through cortical microtubules remain to be fully determined. Our recent study in xylem vessel cells revealed that a mutual inhibitory interaction between cortical microtubules and distinct plasma membrane domains leads to distinctive patterning in secondary cell walls. Our research revealed that the recycling of active and inactive ROP proteins by a specific GAP and GEF pair establishes distinct de novo plasma membrane domains. Active ROP recruits a plant-specific microtubule-associated protein, MIDD1, which mediates the mutual interaction between cortical microtubules and plasma membrane domains. In this mini review, we summarize recent research regarding secondary wall patterning, with a focus on the emerging interplay between plasma membrane domains and cortical microtubules through MIDD1 and ROP.

  6. Griseofulvin stabilizes microtubule dynamics, activates p53 and inhibits the proliferation of MCF-7 cells synergistically with vinblastine

    International Nuclear Information System (INIS)

    Rathinasamy, Krishnan; Jindal, Bhavya; Asthana, Jayant; Singh, Parminder; Balaji, Petety V; Panda, Dulal

    2010-01-01

    Griseofulvin, an antifungal drug, has recently been shown to inhibit proliferation of various types of cancer cells and to inhibit tumor growth in athymic mice. Due to its low toxicity, griseofulvin has drawn considerable attention for its potential use in cancer chemotherapy. This work aims to understand how griseofulvin suppresses microtubule dynamics in living cells and sought to elucidate the antimitotic and antiproliferative action of the drug. The effects of griseofulvin on the dynamics of individual microtubules in live MCF-7 cells were measured by confocal microscopy. Immunofluorescence microscopy, western blotting and flow cytometry were used to analyze the effects of griseofulvin on spindle microtubule organization, cell cycle progression and apoptosis. Further, interactions of purified tubulin with griseofulvin were studied in vitro by spectrophotometry and spectrofluorimetry. Docking analysis was performed using autodock4 and LigandFit module of Discovery Studio 2.1. Griseofulvin strongly suppressed the dynamic instability of individual microtubules in live MCF-7 cells by reducing the rate and extent of the growing and shortening phases. At or near half-maximal proliferation inhibitory concentration, griseofulvin dampened the dynamicity of microtubules in MCF-7 cells without significantly disrupting the microtubule network. Griseofulvin-induced mitotic arrest was associated with several mitotic abnormalities like misaligned chromosomes, multipolar spindles, misegregated chromosomes resulting in cells containing fragmented nuclei. These fragmented nuclei were found to contain increased concentration of p53. Using both computational and experimental approaches, we provided evidence suggesting that griseofulvin binds to tubulin in two different sites; one site overlaps with the paclitaxel binding site while the second site is located at the αβ intra-dimer interface. In combination studies, griseofulvin and vinblastine were found to exert synergistic

  7. Structure of Dynamic, Taxol-Stabilized, and GMPPCP-Stabilized Microtubule.

    Science.gov (United States)

    Ginsburg, Avi; Shemesh, Asaf; Millgram, Abigail; Dharan, Raviv; Levi-Kalisman, Yael; Ringel, Israel; Raviv, Uri

    2017-09-14

    Microtubule (MT) is made of αβ-tubulin heterodimers that dynamically assemble into a hollow nanotube composed of straight protofilaments. MT dynamics is facilitated by hydrolysis of guanosine-5'-triphosphate (GTP) and can be inhibited by either anticancer agents like taxol or the nonhydrolyzable GTP analogues like GMPPCP. Using high-resolution synchrotron X-ray scattering, we have measured and analyzed the scattering curves from solutions of dynamic MT (in other words, in the presence of excess GTP and free of dynamic-inhibiting agents) and examined the effect of two MT stabilizers: taxol and GMPPCP. Previously, we have analyzed the structure of dynamic MT by docking the atomic model of tubulin dimer onto a 3-start left handed helical lattice, derived from the PDB ID 3J6F . 3J6F corresponds to a MT with 14 protofilaments. In this paper, we took into account the possibility of having MT structures containing between 12 and 15 protofilaments. MTs with 12 protofilaments were never observed. We determined the radii, the pitch, and the distribution of protofilament number that best fit the scattering data from dynamic MT or stabilized MT by taxol or GMPPCP. We found that the protofilament number distribution shifted when the MT was stabilized. Taxol increased the mass fraction of MT with 13 protofilaments and decreased the mass fraction of MT with 14 protofilaments. GMPPCP reduced the mass fraction of MT with 15 protofilaments and increased the mass fraction of MT with 14 protofilaments. The pitch, however, remained unchanged regardless of whether the MT was dynamic or stabilized. Higher tubulin concentrations increased the fraction of dynamic MT with 14 protofilaments.

  8. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Directory of Open Access Journals (Sweden)

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  9. Dynamic microtubule organization and mitochondrial transport are regulated by distinct Kinesin-1 pathways

    Directory of Open Access Journals (Sweden)

    Anna Melkov

    2015-12-01

    Full Text Available The microtubule (MT plus-end motor kinesin heavy chain (Khc is well known for its role in long distance cargo transport. Recent evidence showed that Khc is also required for the organization of the cellular MT network by mediating MT sliding. We found that mutations in Khc and the gene of its adaptor protein, kinesin light chain (Klc resulted in identical bristle morphology defects, with the upper part of the bristle being thinner and flatter than normal and failing to taper towards the bristle tip. We demonstrate that bristle mitochondria transport requires Khc but not Klc as a competing force to dynein heavy chain (Dhc. Surprisingly, we demonstrate for the first time that Dhc is the primary motor for both anterograde and retrograde fast mitochondria transport. We found that the upper part of Khc and Klc mutant bristles lacked stable MTs. When following dynamic MT polymerization via the use of GFP-tagged end-binding protein 1 (EB1, it was noted that at Khc and Klc mutant bristle tips, dynamic MTs significantly deviated from the bristle parallel growth axis, relative to wild-type bristles. We also observed that GFP-EB1 failed to concentrate as a focus at the tip of Khc and Klc mutant bristles. We propose that the failure of bristle tapering is due to defects in directing dynamic MTs at the growing tip. Thus, we reveal a new function for Khc and Klc in directing dynamic MTs during polarized cell growth. Moreover, we also demonstrate a novel mode of coordination in mitochondrial transport between Khc and Dhc.

  10. Non-critical string theory formulation of microtubule dynamics and quantum aspects of brain function

    CERN Document Server

    Mavromatos, Nikolaos E

    1995-01-01

    Microtubule (MT) networks, subneural paracrystalline cytosceletal structures, seem to play a fundamental role in the neurons. We cast here the complicated MT dynamics in the form of a 1+1-dimensional non-critical string theory, thus enabling us to provide a consistent quantum treatment of MTs, including enviromental {\\em friction} effects. We suggest, thus, that the MTs are the microsites, in the brain, for the emergence of stable, macroscopic quantum coherent states, identifiable with the {\\em preconscious states}. Quantum space-time effects, as described by non-critical string theory, trigger then an {\\em organized collapse} of the coherent states down to a specific or {\\em conscious state}. The whole process we estimate to take {\\cal O}(1\\,{\\rm sec}), in excellent agreement with a plethora of experimental/observational findings. The {\\em microscopic arrow of time}, endemic in non-critical string theory, and apparent here in the self-collapse process, provides a satisfactory and simple resolution to the age...

  11. Microtubule plus end-tracking proteins play critical roles in directional growth of hyphae by regulating the dynamics of cytoplasmic microtubules in Aspergillus nidulans.

    Science.gov (United States)

    Zeng, Cui J Tracy; Kim, Hye-Ryun; Vargas Arispuro, Irasema; Kim, Jung-Mi; Huang, An-Chi; Liu, Bo

    2014-11-01

    Cytoplasmic microtubules (MTs) serve as a rate-limiting factor for hyphal tip growth in the filamentous fungus Aspergillus nidulans. We hypothesized that this function depended on the MT plus end-tracking proteins (+TIPs) including the EB1 family protein EBA that decorated the MT plus ends undergoing polymerization. The ebAΔ mutation reduced colony growth and the mutant hyphae appeared in an undulating pattern instead of exhibiting unidirectional growth in the control. These phenotypes were enhanced by a mutation in another +TIP gene clipA. EBA was required for plus end-tracking of CLIPA, the Kinesin-7 motor KipA, and the XMAP215 homologue AlpA. In addition, cytoplasmic dynein also depended on EBA to track on most polymerizing MT plus ends, but not for its conspicuous appearance at the MT ends near the hyphal apex. The loss of EBA reduced the number of cytoplasmic MTs and prolonged dwelling times for MTs after reaching the hyphal apex. Finally, we found that colonies were formed in the absence of EBA, CLIPA, and NUDA together, suggesting that they were dispensable for fundamental functions of MTs. This study provided a comprehensive delineation of the relationship among different +TIPs and their contributions to MT dynamics and unidirectional hyphal expansion in filamentous fungi. © 2014 John Wiley & Sons Ltd.

  12. Microtubule dynamics of the centrosome-like polar organizers from the basal land plant Marchantia polymorpha.

    Science.gov (United States)

    Buschmann, Henrik; Holtmannspötter, Michael; Borchers, Agnes; O'Donoghue, Martin-Timothy; Zachgo, Sabine

    2016-02-01

    The liverwort Marchantia employs both modern and ancestral devices during cell division: it forms preprophase bands and in addition it shows centrosome-like polar organizers. We investigated whether polar organizers and preprophase bands cooperate to set up the division plane. To this end, two novel green fluorescent protein-based microtubule markers for dividing cells of Marchantia were developed. Cells of the apical notch formed polar organizers first and subsequently assembled preprophase bands. Polar organizers were formed de novo from multiple mobile microtubule foci localizing to the nuclear envelope. The foci then became concentrated by bipolar aggregation. We determined the comet production rate of polar organizers and show that microtubule plus ends of astral microtubules polymerize faster than those found on cortical microtubules. Importantly, it was observed that conditions increasing polar organizer numbers interfere with preprophase band formation. The data show that polar organizers have much in common with centrosomes, but that they also have specialized features. The results suggest that polar organizers contribute to preprophase band formation and in this way are involved in controlling the division plane. Our analyses of the basal land plant Marchantia shed new light on the evolution of plant cell division. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  13. CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions

    DEFF Research Database (Denmark)

    Shahbazi, Marta N; Megias, Diego; Epifano, Carolina

    2013-01-01

    Classical cadherins and their connections with microtubules (MTs) are emerging as important determinants of cell adhesion. However, the functional relevance of such interactions and the molecular players that contribute to tissue architecture are still emerging. In this paper, we report that the ...

  14. The long-run price sensitivity dynamics of industrial and residential electricity demand: The impact of deregulating electricity prices

    International Nuclear Information System (INIS)

    Adom, Philip Kofi

    2017-01-01

    This study examines the demand-side of Ghana's electricity sector. We test two important related hypotheses: (1) deregulation of electricity price does not promote energy conservation, and (2) demand-price relationship is not an inverted U-shaped. The Stock and Watson dynamic OLS is used to address the so-called second-order bias. The result showed that, deregulation of electricity price in Ghana has induced behaviours that are more consistent with energy conservation improvements. The demand-price relationship is an inverted U, which suggests that there is a price range that end-users can tolerate further price rise and still increase their consumption of electricity. However, the degree of price tolerability is higher for residential consumers than industrial consumers. The simulation results showed that, further economic growth is likely to compromise energy conservation but more in the industrial sector than the residential sector. On the other hand, future crude oil price is likely to deteriorate energy conservation in the initial years after 2016, but this trend is likely to reverse after the year 2020. Pricing mechanisms are potent to induce energy conservation but inadequate. The results suggest that they should be complemented with other stringent policies such as a mandatory energy reduction policy, investment in renewables, and personalization of energy efficiency programs. - Highlights: • Studies the demand-side of the electricity sector • Deregulating electricity price promotes energy conservation • Demand-price relationship is an inverted U-shaped • Pricing policies should be combined with other energy mandatory reduction policies

  15. Insight into microtubule destabilization mechanism of 3,4,5-trimethoxyphenyl indanone derivatives using molecular dynamics simulation and conformational modes analysis

    Science.gov (United States)

    Tripathi, Shubhandra; Srivastava, Gaurava; Singh, Aastha; Prakasham, A. P.; Negi, Arvind S.; Sharma, Ashok

    2018-03-01

    Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αβ-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.

  16. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  17. Electrical deregulation

    International Nuclear Information System (INIS)

    Simpson, R.

    2001-01-01

    Deregulation in the electricity sector took effect on January 1, 2001 in Alberta. Business consumers discovered that their electricity rates had almost doubled in a one-month period. The government argued that it was the case of short term pain for long term gain. The intent of the deregulation is the lowering of prices through competition. This principle applies when the supply meets the demand, but when the demand exceeds the supply, prices increase. When initial plans were made for the deregulation of the sector, utilities did not invest huge amounts of capital to build new generation plants, as it was not known how they would fare in the deregulated environment. This situation was compounded by the fact that there was an economic boom around the same time in Alberta, adding to the demands made on the existing generation infrastructure (approximately 4 per cent per year over the past decade). At the moment, some resource developers such as Syncrude, Amoco, and Daishowa produce their own electricity and export their excess capacity to the provincial grid for general use. The rules of the deregulated market have been clarified and a number of utilities are planning new generation plants and facilities. TransAlta, EPCOR, and Enmax Corp. have announced plans to expand or build new coal-fired plants. Alberta has an estimated 35 billion tonnes of recoverable coal, and 25 million tonnes of coal were used in 1999 to produce 75 per cent of the electricity required in Alberta. Over the next ten years, 4,000 megawatts of new capacity is planned, representing a 50 per cent increase over current levels. AES Corporation, a Virginia power giant, has also announced plans to build a generator in Alberta

  18. Cooperative consumers in a deregulated electricity market - dynamic consumption strategies and price coordination

    Energy Technology Data Exchange (ETDEWEB)

    Haemaelaeinen, R.P.; Maentysaari, J. [Helsinki Univ. of Technology (Finland). Systems Analysis Lab.; Ruusunen, J. [Fortum Power and Heat Inc. (Finland); Pineau, P.O. [Helsinki Univ. of Technology (Finland). Systems Analysis Lab.; Ecole des Hautes Etudes Commerciales, Monteal , Quebec (Canada)

    2000-09-01

    As the trend in electricity markets is strongly towards deregulation, new players, new rules and new behaviors will continue to emerge. One of the new developments on the demand side is purchases made by a coalition of consumers. It seems indeed likely that in the future this will be more common, and that coalitions of consumers will emerge when they are worthwhile. The aim of this paper is to study how such an organization of consumers can be set up in a hierarchical framework. This new approach has not been described before in the deregulated electricity markets but is clearly an important research topic. We focus our interest on electric space heating, which is an energy need especially important in the Nordic countries such as Finland. We examine the consumption strategies of individual electricity buyers within a coalition. The decision problem all consumers face is to find the optimal use of their space heating system with respect to changes in electricity prices and to their tolerance to indoor temperature variation. A mathematical model for this problem is defined. Physical parameters of sample houses were gathered from an experimental field test conducted in Helsinki during the winter of 1996. The coalition buys in the market at marginal cost. However, as marginal cost pricing may not always fulfill metering and communication needs of the members of the coalition, we consider Time-Of-Use (TOU) pricing within the coalition. Different groups of consumer behavior are constructed to simulate this coalition. The optimal marginal price is used as a reference point to estimate the nearest TOU price within the coalition. (author)

  19. Telecommunications Deregulation

    OpenAIRE

    Jerry A. Hausman; William E. Taylor

    2012-01-01

    From Fred Kahn's writings and experiences as a telecommunications regulator and commenter, we draw the following conclusions: prices must be informed by costs; costs are actual incremental costs; costs and prices are an outcome of a Schumpeterian competitive process, not the starting point; excluding incumbents from markets is fundamentally anticompetitive; and a regulatory transition to deregulation entails propensities to micromanage the process to generate preferred outcomes, visible compe...

  20. Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase.

    Science.gov (United States)

    Moss, David K; Wilde, Andrew; Lane, Jon D

    2009-03-01

    During apoptosis, the interphase microtubule network is dismantled then later replaced by a novel, non-centrosomal microtubule array. These microtubules assist in the peripheral redistribution of nuclear fragments in the apoptotic cell; however, the regulation of apoptotic microtubule assembly is not understood. Here, we demonstrate that microtubule assembly depends upon the release of nuclear RanGTP into the apoptotic cytoplasm because this process is blocked in apoptotic cells overexpressing dominant-negative GDP-locked Ran (T24N). Actin-myosin-II contractility provides the impetus for Ran release and, consequently, microtubule assembly is blocked in blebbistatin- and Y27632-treated apoptotic cells. Importantly, the spindle-assembly factor TPX2 (targeting protein for Xklp2), colocalises with apoptotic microtubules, and siRNA silencing of TPX2, but not of the microtubule motors Mklp1 and Kid, abrogates apoptotic microtubule assembly. These data provide a molecular explanation for the assembly of the apoptotic microtubule network, and suggest important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation.

  1. Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends

    Energy Technology Data Exchange (ETDEWEB)

    Ti, Shih-Chieh; Pamula, Melissa C.; Howes, Stuart C.; Duellberg, Christian; Cade, Nicholas I.; Kleiner, Ralph E.; Forth, Scott; Surrey, Thomas; Nogales, Eva; Kapoor, Tarun M.

    2016-04-01

    The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. In this research, we have purified and characterized tubulin heterodimers that have human β-tubulin isotype III (TUBB3), as well as heterodimers with one of two β-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.

  2. Natural gas and deregulation

    International Nuclear Information System (INIS)

    Maisonnier, G.

    2001-01-01

    The gas market is progressively moving towards new organizations under the effect of the deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European union. Within the framework provided by this overall trend, Cedigaz proposes this study in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appear to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed on the European market, for example. Our analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Whenever possible, concrete examples are provided for a closer understanding of this complex subject. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by politics, the regulator and the industrial players. This obviously means a dynamic and constantly evolving process, making it a highly complex process. This report aims to shed some light on the subject. (author)

  3. Dynamics of competitive strategies in de-regulated industries: the case of the electricity industry in France

    International Nuclear Information System (INIS)

    Cateura, O.

    2007-11-01

    This research work is focused on the competitive dynamics approach and rivalry studies between competitors. It develops theses recent perspectives and particularly multi-market competition (also called multipoint competition) in de-regulated industries (network utilities). Indeed, competitive behaviours in liberalized industries are still badly-known. To conduct this research, we decided to analyze a selection of companies (EDF, Electrabel, Endesa, Enel, Gaz de France, Poweo, Direct Energie..) settled on the French electricity market presently in the course of liberalization (1996 - 2006). This qualitative research, through longitudinal case studies, has been developed thanks to a CIFRE agreement (between the French Ministry of Research and the firm Electrabel France) including action research and participant observation. Using multidimensional strategic sequences, we identified two periods, the first one characterized by a confrontation movement and a second one by mutual forbearance. We argue that after learning the rules of a newly liberalized market (confrontation, diversification, internationalization), competitors rapidly and collectively shift there positions towards a focused European strategy based on the gas-electricity convergence. The development of multi-market competition has conducted to mutual forbearance, which was particularly profitable to the major participants. Integrated strategy (market and non-market) appears as an important driver for legitimizing theses behaviours. (author)

  4. Cell cycle-dependent microtubule-based dynamic transport of cytoplasmic dynein in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Takuya Kobayashi

    Full Text Available BACKGROUND: Cytoplasmic dynein complex is a large multi-subunit microtubule (MT-associated molecular motor involved in various cellular functions including organelle positioning, vesicle transport and cell division. However, regulatory mechanism of the cell-cycle dependent distribution of dynein has not fully been understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we report live-cell imaging of cytoplasmic dynein in HeLa cells, by expressing multifunctional green fluorescent protein (mfGFP-tagged 74-kDa intermediate chain (IC74. IC74-mfGFP was successfully incorporated into functional dynein complex. In interphase, dynein moved bi-directionally along with MTs, which might carry cargos such as transport vesicles. A substantial fraction of dynein moved toward cell periphery together with EB1, a member of MT plus end-tracking proteins (+TIPs, suggesting +TIPs-mediated transport of dynein. In late-interphase and prophase, dynein was localized at the centrosomes and the radial MT array. In prometaphase and metaphase, dynein was localized at spindle MTs where it frequently moved from spindle poles toward chromosomes or cell cortex. +TIPs may be involved in the transport of spindle dyneins. Possible kinetochore and cortical dyneins were also observed. CONCLUSIONS AND SIGNIFICANCE: These findings suggest that cytoplasmic dynein is transported to the site of action in preparation for the following cellular events, primarily by the MT-based transport. The MT-based transport may have greater advantage than simple diffusion of soluble dynein in rapid and efficient transport of the limited concentration of the protein.

  5. MVL-PLA2, a snake venom phospholipase A2, inhibits angiogenesis through an increase in microtubule dynamics and disorganization of focal adhesions.

    Directory of Open Access Journals (Sweden)

    Amine Bazaa

    Full Text Available Integrins are essential protagonists of the complex multi-step process of angiogenesis that has now become a major target for the development of anticancer therapies. We recently reported and characterized that MVL-PLA2, a novel phospholipase A2 from Macrovipera lebetina venom, exhibited anti-integrin activity. In this study, we show that MVL-PLA2 also displays potent anti-angiogenic properties. This phospholipase A2 inhibited adhesion and migration of human microvascular-endothelial cells (HMEC-1 in a dose-dependent manner without being cytotoxic. Using Matrigel and chick chorioallantoic membrane assays, we demonstrated that MVL-PLA2, as well as its catalytically inactivated form, significantly inhibited angiogenesis both in vitro and in vivo. We have also found that the actin cytoskeleton and the distribution of alphav beta3 integrin, a critical regulator of angiogenesis and a major component of focal adhesions, were disturbed after MVL-PLA2 treatment. In order to further investigate the mechanism of action of this protein on endothelial cells, we analyzed the dynamic instability behavior of microtubules in living endothelial cells. Interestingly, we showed that MVL-PLA2 significantly increased microtubule dynamicity in HMEC-1 cells by 40%. We propose that the enhancement of microtubule dynamics may explain the alterations in the formation of focal adhesions, leading to inhibition of cell adhesion and migration.

  6. Models for microtubule cargo transport coupling the Langevin equation to stochastic stepping motor dynamics: Caring about fluctuations.

    Science.gov (United States)

    Bouzat, Sebastián

    2016-01-01

    One-dimensional models coupling a Langevin equation for the cargo position to stochastic stepping dynamics for the motors constitute a relevant framework for analyzing multiple-motor microtubule transport. In this work we explore the consistence of these models focusing on the effects of the thermal noise. We study how to define consistent stepping and detachment rates for the motors as functions of the local forces acting on them in such a way that the cargo velocity and run-time match previously specified functions of the external load, which are set on the base of experimental results. We show that due to the influence of the thermal fluctuations this is not a trivial problem, even for the single-motor case. As a solution, we propose a motor stepping dynamics which considers memory on the motor force. This model leads to better results for single-motor transport than the approaches previously considered in the literature. Moreover, it gives a much better prediction for the stall force of the two-motor case, highly compatible with the experimental findings. We also analyze the fast fluctuations of the cargo position and the influence of the viscosity, comparing the proposed model to the standard one, and we show how the differences on the single-motor dynamics propagate to the multiple motor situations. Finally, we find that the one-dimensional character of the models impede an appropriate description of the fast fluctuations of the cargo position at small loads. We show how this problem can be solved by considering two-dimensional models.

  7. Recruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont

    KAUST Repository

    Woods, Kerry L.

    2013-05-09

    The apicomplexan parasite Theileria annulata transforms infected host cells, inducing uncontrolled proliferation and clonal expansion of the parasitized cell population. Shortly after sporozoite entry into the target cell, the surrounding host cell membrane is dissolved and an array of host cell microtubules (MTs) surrounds the parasite, which develops into the transforming schizont. The latter does not egress to invade and transform other cells. Instead, it remains tethered to host cell MTs and, during mitosis and cytokinesis, engages the cell\\'s astral and central spindle MTs to secure its distribution between the two daughter cells. The molecular mechanism by which the schizont recruits and stabilizes host cell MTs is not known. MT minus ends are mostly anchored in the MT organizing center, while the plus ends explore the cellular space, switching constantly between phases of growth and shrinkage (called dynamic instability). Assuming the plus ends of growing MTs provide the first point of contact with the parasite, we focused on the complex protein machinery associated with these structures. We now report how the schizont recruits end-binding protein 1 (EB1), a central component of the MT plus end protein interaction network and key regulator of host cell MT dynamics. Using a range of in vitro experiments, we demonstrate that T. annulata p104, a polymorphic antigen expressed on the schizont surface, functions as a genuine EB1-binding protein and can recruit EB1 in the absence of any other parasite proteins. Binding strictly depends on a consensus SxIP motif located in a highly disordered C-terminal region of p104. We further show that parasite interaction with host cell EB1 is cell cycle regulated. This is the first description of a pathogen-encoded protein to interact with EB1 via a bona-fide SxIP motif. Our findings provide important new insight into the mode of interaction between Theileria and the host cell cytoskeleton. 2013 Woods et al.

  8. Recruitment of EB1, a master regulator of microtubule dynamics, to the surface of the Theileria annulata schizont.

    Directory of Open Access Journals (Sweden)

    Kerry L Woods

    2013-05-01

    Full Text Available The apicomplexan parasite Theileria annulata transforms infected host cells, inducing uncontrolled proliferation and clonal expansion of the parasitized cell population. Shortly after sporozoite entry into the target cell, the surrounding host cell membrane is dissolved and an array of host cell microtubules (MTs surrounds the parasite, which develops into the transforming schizont. The latter does not egress to invade and transform other cells. Instead, it remains tethered to host cell MTs and, during mitosis and cytokinesis, engages the cell's astral and central spindle MTs to secure its distribution between the two daughter cells. The molecular mechanism by which the schizont recruits and stabilizes host cell MTs is not known. MT minus ends are mostly anchored in the MT organizing center, while the plus ends explore the cellular space, switching constantly between phases of growth and shrinkage (called dynamic instability. Assuming the plus ends of growing MTs provide the first point of contact with the parasite, we focused on the complex protein machinery associated with these structures. We now report how the schizont recruits end-binding protein 1 (EB1, a central component of the MT plus end protein interaction network and key regulator of host cell MT dynamics. Using a range of in vitro experiments, we demonstrate that T. annulata p104, a polymorphic antigen expressed on the schizont surface, functions as a genuine EB1-binding protein and can recruit EB1 in the absence of any other parasite proteins. Binding strictly depends on a consensus SxIP motif located in a highly disordered C-terminal region of p104. We further show that parasite interaction with host cell EB1 is cell cycle regulated. This is the first description of a pathogen-encoded protein to interact with EB1 via a bona-fide SxIP motif. Our findings provide important new insight into the mode of interaction between Theileria and the host cell cytoskeleton.

  9. SAS-4 is recruited to a dynamic structure in newly forming centrioles that is stabilized by the gamma-tubulin-mediated addition of centriolar microtubules.

    Science.gov (United States)

    Dammermann, Alexander; Maddox, Paul S; Desai, Arshad; Oegema, Karen

    2008-02-25

    Centrioles are surrounded by pericentriolar material (PCM), which is proposed to promote new centriole assembly by concentrating gamma-tubulin. Here, we quantitatively monitor new centriole assembly in living Caenorhabditis elegans embryos, focusing on the conserved components SAS-4 and SAS-6. We show that SAS-4 and SAS-6 are coordinately recruited to the site of new centriole assembly and reach their maximum levels during S phase. Centriolar SAS-6 is subsequently reduced by a mechanism intrinsic to the early assembly pathway that does not require progression into mitosis. Centriolar SAS-4 remains in dynamic equilibrium with the cytoplasmic pool until late prophase, when it is stably incorporated in a step that requires gamma-tubulin and microtubule assembly. These results indicate that gamma-tubulin in the PCM stabilizes the nascent daughter centriole by promoting microtubule addition to its outer wall. Such a mechanism may help restrict new centriole assembly to the vicinity of preexisting parent centrioles that recruit PCM.

  10. Microtubules self-repair in response to mechanical stress

    Science.gov (United States)

    Schaedel, Laura; John, Karin; Gaillard, Jérémie; Nachury, Maxence V.; Blanchoin, Laurent; Théry, Manuel

    2015-11-01

    Microtubules--which define the shape of axons, cilia and flagella, and provide tracks for intracellular transport--can be highly bent by intracellular forces, and microtubule structure and stiffness are thought to be affected by physical constraints. Yet how microtubules tolerate the vast forces exerted on them remains unknown. Here, by using a microfluidic device, we show that microtubule stiffness decreases incrementally with each cycle of bending and release. Similar to other cases of material fatigue, the concentration of mechanical stresses on pre-existing defects in the microtubule lattice is responsible for the generation of more extensive damage, which further decreases microtubule stiffness. Strikingly, damaged microtubules were able to incorporate new tubulin dimers into their lattice and recover their initial stiffness. Our findings demonstrate that microtubules are ductile materials with self-healing properties, that their dynamics does not exclusively occur at their ends, and that their lattice plasticity enables the microtubules' adaptation to mechanical stresses.

  11. Dynamic Recruitment of Cdc2 to Specific Microtubule Structures during Mitosis

    Czech Academy of Sciences Publication Activity Database

    Weingartner, M.; Binarová, Pavla; Dryková, Denisa; Achweighofer, A.; David, P.; Heberle, E.; Doonan, J.; Bogre, L.

    2001-01-01

    Roč. 13, - (2001), s. 1929-1943 ISSN 1040-4651 R&D Projects: GA AV ČR IAA5020803 Grant - others:XE(XC) GA QLRT-00454 Keywords : dynamic * recruitment * specific Subject RIV: EE - Microbiology, Virology Impact factor: 11.081, year: 2001

  12. Assembly and control of large microtubule complexes

    Science.gov (United States)

    Korolev, Kirill; Ishihara, Keisuke; Mitchison, Timothy

    Motility, division, and other cellular processes require rapid assembly and disassembly of microtubule structures. We report a new mechanism for the formation of asters, radial microtubule complexes found in very large cells. The standard model of aster growth assumes elongation of a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we found evidence for microtubule nucleation away from centrosomes. By combining polymerization dynamics and auto-catalytic nucleation of microtubules, we developed a new biophysical model of aster growth. The model predicts an explosive transition from an aster with a steady-state radius to one that expands as a travelling wave. At the transition, microtubule density increases continuously, but aster growth rate discontinuously jumps to a nonzero value. We tested our model with biochemical perturbations in egg extract and confirmed main theoretical predictions including the jump in the growth rate. Our results show that asters can grow even though individual microtubules are short and unstable. The dynamic balance between microtubule collapse and nucleation could be a general framework for the assembly and control of large microtubule complexes. NIH GM39565; Simons Foundation 409704; Honjo International 486 Scholarship Foundation.

  13. Biological Information Processing in Single Microtubules

    Science.gov (United States)

    2014-03-05

    generated by synchronized oscillations of microtubules, centrosomes and chromosomes regulate the dynamics of mitosis and meiosis, Yue Zhao and Qimin...of frequency by a single microtubule. Green arrows depict the peaks that appear in absorption and disappear in transmission. Purple arrows show

  14. Microtubule heterogeneity of Ornithogalum umbellatum ovary epidermal cells: non-stable cortical microtubules and stable lipotubuloid microtubules.

    Science.gov (United States)

    Kwiatkowska, Maria; Stępiński, Dariusz; Polit, Justyna T; Popłońska, Katarzyna; Wojtczak, Agnieszka

    2011-01-01

    Lipotubuloids, structures containing lipid bodies and microtubules, are described in ovary epidermal cells of Ornithogalum umbellatum. Microtubules of lipotubuloids can be fixed in electron microscope fixative containing only buffered OsO(4) or in glutaraldehyde with OsO(4) post-fixation, or in a mixture of OsO(4) and glutaraldehyde. None of these substances fixes cortical microtubules of ovary epidermis of this plant which is characterized by dynamic longitudinal growth. However, cortical microtubules can be fixed with cold methanol according immunocytological methods with the use of β-tubulin antibodies and fluorescein. The existence of cortical microtubules has also been evidenced by EM observations solely after the use of taxol, microtubule stabilizer, and fixation in a glutaraldehyde/OsO(4) mixture. These microtubules mostly lie transversely, sometimes obliquely, and rarely parallel to the cell axis. Staining, using Ruthenium Red and silver hexamine, has revealed that lipotubuloid microtubules surface is covered with polysaccharides. The presumption has been made that the presence of a polysaccharide layer enhances the stability of lipotubuloid microtubules.

  15. Microtubule-Organizing Centers.

    Science.gov (United States)

    Wu, Jingchao; Akhmanova, Anna

    2017-10-06

    The organization of microtubule networks is crucial for controlling chromosome segregation during cell division, for positioning and transport of different organelles, and for cell polarity and morphogenesis. The geometry of microtubule arrays strongly depends on the localization and activity of the sites where microtubules are nucleated and where their minus ends are anchored. Such sites are often clustered into structures known as microtubule-organizing centers, which include the centrosomes in animals and spindle pole bodies in fungi. In addition, other microtubules, as well as membrane compartments such as the cell nucleus, the Golgi apparatus, and the cell cortex, can nucleate, stabilize, and tether microtubule minus ends. These activities depend on microtubule-nucleating factors, such as γ-tubulin-containing complexes and their activators and receptors, and microtubule minus end-stabilizing proteins with their binding partners. Here, we provide an overview of the current knowledge on how such factors work together to control microtubule organization in different systems.

  16. Modeling microtubule oscillations

    DEFF Research Database (Denmark)

    Jobs, E.; Wolf, D.E.; Flyvbjerg, H.

    1997-01-01

    Synchronization of molecular reactions in a macroscopic volume may cause the volume's physical properties to change dynamically and thus reveal much about the reactions. As an example, experimental time series for so-called microtubule oscillations are analyzed in terms of a minimal model...... for this complex polymerization-depolymerization cycle. The model reproduces well the qualitatively different time series that result from different experimental conditions, and illuminates the role and importance of individual processes in the cycle. Simple experiments are suggested that can further test...... and define the model and the polymer's reaction cycle....

  17. The use of compressive sensing and peak detection in the reconstruction of microtubules length time series in the process of dynamic instability.

    Science.gov (United States)

    Mahrooghy, Majid; Yarahmadian, Shantia; Menon, Vineetha; Rezania, Vahid; Tuszynski, Jack A

    2015-10-01

    Microtubules (MTs) are intra-cellular cylindrical protein filaments. They exhibit a unique phenomenon of stochastic growth and shrinkage, called dynamic instability. In this paper, we introduce a theoretical framework for applying Compressive Sensing (CS) to the sampled data of the microtubule length in the process of dynamic instability. To reduce data density and reconstruct the original signal with relatively low sampling rates, we have applied CS to experimental MT lament length time series modeled as a Dichotomous Markov Noise (DMN). The results show that using CS along with the wavelet transform significantly reduces the recovery errors comparing in the absence of wavelet transform, especially in the low and the medium sampling rates. In a sampling rate ranging from 0.2 to 0.5, the Root-Mean-Squared Error (RMSE) decreases by approximately 3 times and between 0.5 and 1, RMSE is small. We also apply a peak detection technique to the wavelet coefficients to detect and closely approximate the growth and shrinkage of MTs for computing the essential dynamic instability parameters, i.e., transition frequencies and specially growth and shrinkage rates. The results show that using compressed sensing along with the peak detection technique and wavelet transform in sampling rates reduces the recovery errors for the parameters. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. GDP-tubulin incorporation into growing microtubules modulates polymer stability.

    Science.gov (United States)

    Valiron, Odile; Arnal, Isabelle; Caudron, Nicolas; Job, Didier

    2010-06-04

    Microtubule growth proceeds through the endwise addition of nucleotide-bound tubulin dimers. The microtubule wall is composed of GDP-tubulin subunits, which are thought to come exclusively from the incorporation of GTP-tubulin complexes at microtubule ends followed by GTP hydrolysis within the polymer. The possibility of a direct GDP-tubulin incorporation into growing polymers is regarded as hardly compatible with recent structural data. Here, we have examined GTP-tubulin and GDP-tubulin incorporation into polymerizing microtubules using a minimal assembly system comprised of nucleotide-bound tubulin dimers, in the absence of free nucleotide. We find that GDP-tubulin complexes can efficiently co-polymerize with GTP-tubulin complexes during microtubule assembly. GDP-tubulin incorporation into microtubules occurs with similar efficiency during bulk microtubule assembly as during microtubule growth from seeds or centrosomes. Microtubules formed from GTP-tubulin/GDP-tubulin mixtures display altered microtubule dynamics, in particular a decreased shrinkage rate, apparently due to intrinsic modifications of the polymer disassembly properties. Thus, although microtubules polymerized from GTP-tubulin/GDP-tubulin mixtures or from homogeneous GTP-tubulin solutions are both composed of GDP-tubulin subunits, they have different dynamic properties, and this may reveal a novel form of microtubule "structural plasticity."

  19. An analytical method for solving exact solutions of a nonlinear evolution equation describing the dynamics of ionic currents along microtubules

    Directory of Open Access Journals (Sweden)

    Md. Nur Alam

    2017-11-01

    Full Text Available In this article, a variety of solitary wave solutions are observed for microtubules (MTs. We approach the problem by treating the solutions as nonlinear RLC transmission lines and then find exact solutions of Nonlinear Evolution Equations (NLEEs involving parameters of special interest in nanobiosciences and biophysics. We determine hyperbolic, trigonometric, rational and exponential function solutions and obtain soliton-like pulse solutions for these equations. A comparative study against other methods demonstrates the validity of the technique that we developed and demonstrates that our method provides additional solutions. Finally, using suitable parameter values, we plot 2D and 3D graphics of the exact solutions that we observed using our method. Keywords: Analytical method, Exact solutions, Nonlinear evolution equations (NLEEs of microtubules, Nonlinear RLC transmission lines

  20. Mechanics of microtubules: effects of protofilament orientation.

    Science.gov (United States)

    Donhauser, Zachary J; Jobs, William B; Binka, Edem C

    2010-09-08

    Microtubules are hollow cylindrical polymers of the protein tubulin that play a number of important dynamic and structural roles in eukaryotic cells. Both in vivo and in vitro microtubules can exist in several possible configurations, differing in the number of protofilaments, helical rise of tubulin dimers, and protofilament skew angle with respect to the main tube axis. Here, finite element modeling is applied to examine the mechanical response of several known microtubule types when subjected to radial deformation. The data presented here provide an important insight into microtubule stiffness and reveal that protofilament orientation does not affect radial stiffness. Rather, stiffness is primarily dependent on the effective Young's modulus of the polymerized material and the effective radius of the microtubule. These results are also directly correlated to atomic force microscopy nanoindentation measurements to allow a more detailed interpretation of previous experiments. When combined with experimental data that show a significant difference between microtubules stabilized with a slowly hydrolyzable GTP analog and microtubules stabilized with paclitaxel, the finite element data suggest that paclitaxel increases the overall radial flexibility of the microtubule wall. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Costs of electricity deregulation

    International Nuclear Information System (INIS)

    Woo, C.K.; King, M.

    2006-01-01

    The last decade has witnessed efforts throughout the world to deregulate the electricity industry, with varied results. While there have been a few qualified success stories, many challenges of deregulation have come to light. These challenges can lead to negative, even disastrous, outcomes. Based on a comprehensive literature review, this paper catalogues problems experienced in various deregulation efforts, and considers the application of the lessons learned from this history to Israel, which is considering deregulation. Failings of deregulation are found to center around the following problems: high set-up cost; complicated market design; inevitable spot price volatility; market power abuse; inefficient investment; difficulty in reducing generation cost; dysfunctional input markets; stranded cost; unequal distribution of benefits. We find that many of these problems are exacerbated by the particular circumstances faced by Israel, and advise any country or region considering deregulation to carefully consider these obstacles to success. (author)

  2. Potent antiproliferative cembrenoids accumulate in tobacco upon infection with Rhodococcus fascians and trigger unusual microtubule dynamics in human glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Aminata P Nacoulma

    Full Text Available AIMS: Though plant metabolic changes are known to occur during interactions with bacteria, these were rarely challenged for pharmacologically active compounds suitable for further drug development. Here, the occurrence of specific chemicals with antiproliferative activity against human cancer cell lines was evidenced in hyperplasia (leafy galls induced when plants interact with particular phytopathogens, such as the Actinomycete Rhodococcus fascians. METHODS: We examined leafy galls fraction F3.1.1 on cell proliferation, cell division and cytoskeletal disorganization of human cancer cell lines using time-lapse videomicroscopy imaging, combined with flow cytometry and immunofluorescence analysis. We determined the F3.1.1-fraction composition by gas chromatography coupled to mass spectrometry. RESULTS: The leafy galls induced on tobacco by R. fascians yielded fraction F3.1.1 which inhibited proliferation of glioblastoma U373 cells with an IC50 of 4.5 µg/mL, F.3.1.1 was shown to increase cell division duration, cause nuclear morphological deformations and cell enlargement, and, at higher concentrations, karyokinesis defects leading to polyploidization and apoptosis. F3.1.1 consisted of a mixture of isomers belonging to the cembrenoids. The cellular defects induced by F3.1.1 were caused by a peculiar cytoskeletal disorganization, with the occurrence of fragmented tubulin and strongly organized microtubule aggregates within the same cell. Colchicine, paclitaxel, and cembrene also affected U373 cell proliferation and karyokinesis, but the induced microtubule rearrangement was very different from that provoked by F3.1.1. Altogether our data indicate that the cembrenoid isomers in F3.1.1 have a unique mode of action and are able to simultaneously modulate microtubule polymerization and stability.

  3. Rho-associated coiled-coil kinase (ROCK) protein controls microtubule dynamics in a novel signaling pathway that regulates cell migration.

    Science.gov (United States)

    Schofield, Alice V; Steel, Rohan; Bernard, Ora

    2012-12-21

    The two members of the Rho-associated coiled-coil kinase (ROCK1 and 2) family are established regulators of actin dynamics that are involved in the regulation of the cell cycle as well as cell motility and invasion. Here, we discovered a novel signaling pathway whereby ROCK regulates microtubule (MT) acetylation via phosphorylation of the tubulin polymerization promoting protein 1 (TPPP1/p25). We show that ROCK phosphorylation of TPPP1 inhibits the interaction between TPPP1 and histone deacetylase 6 (HDAC6), which in turn results in increased HDAC6 activity followed by a decrease in MT acetylation. As a consequence, we show that TPPP1 phosphorylation by ROCK increases cell migration and invasion via modulation of cellular acetyl MT levels. We establish here that the ROCK-TPPP1-HDAC6 signaling pathway is important for the regulation of cell migration and invasion.

  4. Microtubules Growth Rate Alteration in Human Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Irina B. Alieva

    2010-01-01

    Full Text Available To understand how microtubules contribute to the dynamic reorganization of the endothelial cell (EC cytoskeleton, we established an EC model expressing EB3-GFP, a protein that marks microtubule plus-ends. Using this model, we were able to measure microtubule growth rate at the centrosome region and near the cell periphery of a single human EC and in the EC monolayer. We demonstrate that the majority of microtubules in EC are dynamic, the growth rate of their plus-ends is highest in the internal cytoplasm, in the region of the centrosome. Growth rate of microtubule plus-ends decreases from the cell center toward the periphery. Our data suggest the existing mechanism(s of local regulation of microtubule plus-ends growth in EC. Microtubule growth rate in the internal cytoplasm of EC in the monolayer is lower than that of single EC suggesting the regulatory effect of cell-cell contacts. Centrosomal microtubule growth rate distribution in single EC indicated the presence of two subpopulations of microtubules with “normal” (similar to those in monolayer EC and “fast” (three times as much growth rates. Our results indicate functional interactions between cell-cell contacts and microtubules.

  5. Effect of radiation on microtubule structure in cancer cells

    International Nuclear Information System (INIS)

    Tripath, Shambhoo Sharan; Panda, Dulal; Jayakumar, S.; Maikho, Thoh; Sandur, Santosh Kumar

    2017-01-01

    Microtubules (MT) are dynamic structural cellular components. In proliferating cells, they are essential components in cell division through the formation of the mitotic spindle. Radiotherapy is an integral part of cancer treatment for most of the solid cancers. Scanty data exists in the literature related to how ionizing radiation affects microtubule reorganization in tumor cells. In the present study, breast cancer cell line (MCF-7 cells) was exposed to different doses of radiation (2-10Gy). Cells were cultured for 24 h, fixed and stained with antitubulin antibody and subjected to immunofluorescence microscopy. In another experiment, cells were subjected to cold treatment for 5 min or 30 min for studying the disassembly of microtubules after 24 h of irradiation. Further, these cells were incubated at 37°C for 20 min for studying the reassembly of microtubules. Acetylation of microtubule was also examined after exposure of cells to radiation. Experiments were also performed by combining radiation with low concentration of CXI-Benzo 84 (MT destabilizing agent 1 and 2.5 uM). Exposure of MCF-7 cells to radiation lead to destabilization of microtubules. Interestingly, destabilization of microtubule was faster upon cold treatment in irradiated group as compared to control group. These cells failed to re-stabilize at 37°C. Radiation also reduced the acetylation level of microtubule. Combination treatment of CXI-Benzo 84 with radiation exhibited additive effect in terms of depolymerization of MT. Our results suggest that ionizing radiation indeed modulates microtubule dynamics. (author)

  6. Microtubules: A network for solitary waves

    Directory of Open Access Journals (Sweden)

    Zdravković Slobodan

    2017-01-01

    Full Text Available In the present paper we deal with nonlinear dynamics of microtubules. The structure and role of microtubules in cells are explained as well as one of models explaining their dynamics. Solutions of the crucial nonlinear differential equation depend on used mathematical methods. Two commonly used procedures, continuum and semi-discrete approximations, are explained. These solutions are solitary waves usually called as kink solitons, breathers and bell-type solitons. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III45010

  7. Power deregulation in Alberta

    International Nuclear Information System (INIS)

    MacMurchy, N.E.

    1999-01-01

    The impacts of deregulation of the electric power industry in Alberta from the perspective of the natural gas industry was presented with special focus on how the power market can be brought back into balance. The issue of what impacts the deregulated power market will have on natural gas consumption or prices was also reviewed. It was noted that deregulation of the electric power industry will have a definite impact on natural gas consumption but no significant impact on prices. It is estimated that in 1999/2000 gas demand will be 90 million cf/day for incremental electricity generation. However, as long as pipe capacity out of the province exits, this increase in natural gas demand in Alberta is not expected to affect gas prices

  8. The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

    DEFF Research Database (Denmark)

    Zhang, Gang; Beati, Hamze; Nilsson, Jakob

    2013-01-01

    Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been...

  9. Multiscale modeling and simulation of microtubule-motor-protein assemblies

    Science.gov (United States)

    Gao, Tong; Blackwell, Robert; Glaser, Matthew A.; Betterton, M. D.; Shelley, Michael J.

    2015-12-01

    Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

  10. Multiscale modeling and simulation of microtubule-motor-protein assemblies.

    Science.gov (United States)

    Gao, Tong; Blackwell, Robert; Glaser, Matthew A; Betterton, M D; Shelley, Michael J

    2015-01-01

    Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

  11. S. pombe kinesins-8 promote both nucleation and catastrophe of microtubules.

    Directory of Open Access Journals (Sweden)

    Muriel Erent

    Full Text Available The kinesins-8 were originally thought to be microtubule depolymerases, but are now emerging as more versatile catalysts of microtubule dynamics. We show here that S. pombe Klp5-436 and Klp6-440 are non-processive plus-end-directed motors whose in vitro velocities on S. pombe microtubules at 7 and 23 nm s(-1 are too slow to keep pace with the growing tips of dynamic interphase microtubules in living S. pombe. In vitro, Klp5 and 6 dimers exhibit a hitherto-undescribed combination of strong enhancement of microtubule nucleation with no effect on growth rate or catastrophe frequency. By contrast in vivo, both Klp5 and Klp6 promote microtubule catastrophe at cell ends whilst Klp6 also increases the number of interphase microtubule arrays (IMAs. Our data support a model in which Klp5/6 bind tightly to free tubulin heterodimers, strongly promoting the nucleation of new microtubules, and then continue to land as a tubulin-motor complex on the tips of growing microtubules, with the motors then dissociating after a few seconds residence on the lattice. In vivo, we predict that only at cell ends, when growing microtubule tips become lodged and their growth slows down, will Klp5/6 motor activity succeed in tracking growing microtubule tips. This mechanism would allow Klp5/6 to detect the arrival of microtubule tips at cells ends and to amplify the intrinsic tendency for microtubules to catastrophise in compression at cell ends. Our evidence identifies Klp5 and 6 as spatial regulators of microtubule dynamics that enhance both microtubule nucleation at the cell centre and microtubule catastrophe at the cell ends.

  12. Taxol crystals can masquerade as stabilized microtubules.

    Directory of Open Access Journals (Sweden)

    Margit Foss

    Full Text Available Taxol is a potent anti-mitotic drug used in chemotherapy, angioplastic stents, and cell biology research. By binding and stabilizing microtubules, Taxol inhibits their dynamics, crucial for cell division, motility, and survival. The drug has also been reported to induce formation of asters and bundles composed of stabilized microtubules. Surprisingly, at commonly used concentrations, Taxol forms crystals that rapidly bind fluorescent tubulin subunits, generating structures with an uncanny resemblance to microtubule asters and bundles. Kinetic and topological considerations suggest that tubulin subunits, rather than microtubules, bind the crystals. This sequestration of tubulin from the subunit pool would be expected to shift the equilibrium of free to polymerized tubulin to disfavor assembly. Our results imply that some previously reported Taxol-induced asters or bundles could include or be composed of tubulin-decorated Taxol crystals. Thus, reevaluation of certain morphological, chemical, and physical properties of Taxol-treated microtubules may be necessary. Moreover, our findings suggest a novel mechanism for chemotherapy-induced cytotoxicity in non-dividing cells, with far-reaching medical implications.

  13. Deregulating electricity in the American states

    Science.gov (United States)

    Terbush, Thomas Lee

    This dissertation develops nine stylized facts that summarize the major consequences of deregulation and tests these against recent experience in the electric utility industry. The experience of the electric utility industry matches the predictions of the stylized facts, except in one instance: although real electricity prices fell between 1982 and 1999, real prices fell less in states that deregulated. This dissertation presents three possible explanations for this discrepancy. First, through dynamic efficiency, consumers may benefit in the long run through lower rates and better service in the electricity market, or deregulation may be a public good that benefits electricity consumers through economy-wide improvements in efficiency. Second, higher prices may be a long-run outcome as predicted by the theory of the second best. Or third, both regulators and utilities may use deregulation to generate new rents. Because the original rents from regulation had dissipated, new rents could be generated under deregulation by making consumers pay off the utilities and then creating more new rents through re-regulation of the industry. Close examination tends to support the first and third explanations, although the second-best explanation cannot yet be ruled out completely. Higher prices appear to be a transitional phenomenon, resulting from a short-term payoff from consumers to incumbent utilities that was required to move deregulation forward. This payoff occurs as residential and commercial consumers bear relatively higher rates over three to five years to compensate utilities for stranded costs, investments thought to be unrecoverable under full competition. All states are benefiting from deregulation, but states that are deregulating are benefiting less while stranded costs are being recovered. This dissertation also examines California electricity deregulation and finds that the experience in California conforms with to the stylized facts, and that certain structural

  14. Airline Deregulation and Public Policy

    Science.gov (United States)

    Morrison, Steven A.; Winston, Clifford

    1989-08-01

    An assessment of the effects of airline deregulation on travelers and carriers indicates that deregulation has provided travelers and carriers with 14.9 billion of annual benefits (1988 dollars). Airport congestion, airline safety, airline bankruptcy, and mergers are also analyzed and found in most cases to have reduced benefits. But, these costs should not be attributed to deregulation per se, but to failures by the government to pursue appropriate policies in these areas. Pursuit of policies that promote airline competition and efficient use of airport capacity would significantly increase the benefits from deregulation and would provide valuable guidance for other industries undergoing the transition to deregulation.

  15. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    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

  16. Electric deregulation in Canada

    International Nuclear Information System (INIS)

    Way, R.W.

    1996-01-01

    An outline of the electric power deregulation activities across Canada, particularly in Alberta, British Columbia, and Ontario, was presented. A central element of the restructuring is creation of a power pool which acts as an open spot market, and a transmission administrator that provides access to the generators, distribution companies, importers and exporters. Load forecasts, average daily load profile and hourly pool prices for TransAlta Corporation were presented as an example. 22 figs

  17. Natural gas deregulation

    International Nuclear Information System (INIS)

    Ronchi, M.

    1993-01-01

    With the aim of establishing realistic options for deregulation in the natural gas industry, this paper first considers the structural evolution of this industry and evidences how it differs from the petroleum industry with which it exhibits some essential characteristics in common. This comparison is made in order to stress that, contrary to popular belief, that which is without doubt good for the petroleum industry is not necessarily so also for the natural gas industry. The paper concludes with separate analyses of the natural gas markets in the principal industrialized countries. Arguments are provided to show that the 'soft' deregulation option for the natural gas industry is not feasible, and that 'total' deregulation instead, backed by the passing of a suitable package of anti-trust laws 'unbundling' the industry's four major activities, i.e., production, storage, primary and secondary distribution, is the preferable option. The old concept of guaranteed supplies for minor users of natural gas should give way to the laws of supply and demand governing inter-fuel competition ensured through the strict supervision of vigilance committees

  18. Expansion and Polarity Sorting in Microtubule-Dynein Bundles(WHAT IS LIFE? THE NEXT 100 YEARS OF YUKAWA'S DREAM)

    OpenAIRE

    Assaf, ZEMEL; Alex, MOGILNER; Department of Neurobiology, Physiology and Behavior, University of California; Department of Neurobiology, Physiology and Behavior, University of California

    2008-01-01

    Interactions of multiple molecular motors with dynamic polymers, such as actin and microtubules, form the basis for many processes in the cell cytoskeleton. One example is the active 'sorting' of microtubule bundles by dynein molecular motors into aster-like arrays of microtubules; in these bundles dynein motors cross-link and slide neighboring microtubules apart. A number of models have been suggested to quantify the active dynamics of cross-linked bundles of polar filaments. In the case of ...

  19. Electrodynamic effects on microtubules

    Czech Academy of Sciences Publication Activity Database

    Kučera, Ondřej; Havelka, Daniel; Deriu, M.A.; Cifra, Michal

    2015-01-01

    Roč. 44, Jul (2015), s. 169-169 ISSN 0175-7571. [10th European-Biophysical-Societies-Association (EBSA) European Biophysics Congress. 18.07.2015-22.07.2015, Dresden] R&D Projects: GA ČR(CZ) GA15-17102S Institutional support: RVO:67985882 Keywords : Microtubules * Electric al polarity Subject RIV: JA - Electronics ; Optoelectronics, Electric al Engineering

  20. Microtubule's conformational cap

    DEFF Research Database (Denmark)

    Flyvbjerg, H.

    1999-01-01

    The molecular mechanisms that allow elongation of the unstable microtubule lattice remain unclear. It is usually thought that the GDP-liganded tubulin lattice is capped by a small layer of GTP- or GDP-P(i)-liganded molecules, the so called "GTP-cap". Here, we point-out that the elastic properties...

  1. The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila

    Science.gov (United States)

    Duncan, Jason E.; Lytle, Nikki K.; Zuniga, Alfredo; Goldstein, Lawrence S. B.

    2013-01-01

    Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai) gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila . The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila , which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila , we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport. PMID:23840848

  2. Synchronous Oscillations in Microtubule Polymerization

    Science.gov (United States)

    Carlier, M. F.; Melki, R.; Pantaloni, D.; Hill, T. L.; Chen, Y.

    1987-08-01

    Under conditions where microtubule nucleation and growth are fast (i.e., high magnesium ion and tubulin concentrations and absence of glycerol), microtubule assembly in vitro exhibits an oscillatory regime preceding the establishment of steady state. The amplitude of the oscillations can represent >50% of the maximum turbidity change and oscillations persist for up to 20 periods of 80 s each. Oscillations are accompanied by extensive length redistribution of microtubules. Preliminary work suggests that the oscillatory kinetics can be simulated using a model in which many microtubules undergo synchronous transitions between growing and rapidly depolymerizing phases, complicated by the kinetically limiting rate of nucleotide exchange on free tubulin.

  3. Reactor decommissioning in a deregulated market

    International Nuclear Information System (INIS)

    Beverridge, George; Cooper, T.

    2002-01-01

    Full text: Deregulation of the electricity markets in North America and Western Europe has had many profound effects on the electric utilities and the nuclear industry. Deregulation has led to cost transparency, increased competition, and a drive by the utilities to reduce costs in order to maintain market share and margins. In the context of this more competitive and dynamic market having a clear picture of decommissioning liabilities and their successful discharge has a material impact on the financial performance of a utility. This paper will summarise BNFL Environmental Services' experience with regard to its experience in both the planning and implementation phases of a reactor decommissioning project. In particular it will demonstrate how commercial projects in crucial areas of strategy development, project implementation and site restoration, can be combined with an approach that is both commercial and innovative to reduce the risks to a utility. This paper sets out to demonstrate this viewpoint. (author)

  4. Capture of microtubule plus-ends at the actin cortex promotes axophilic neuronal migration by enhancing microtubule tension in the leading process.

    Science.gov (United States)

    Hutchins, B Ian; Wray, Susan

    2014-01-01

    Microtubules are a critical part of neuronal polarity and leading process extension, thus microtubule movement plays an important role in neuronal migration. However, the dynamics of microtubules during the forward movement of the nucleus into the leading process (nucleokinesis) is unclear and may be dependent on the cell type and mode of migration used. In particular, little is known about cytoskeletal changes during axophilic migration, commonly used in anteroposterior neuronal migration. We recently showed that leading process actin flow in migrating GnRH neurons is controlled by a signaling cascade involving IP3 receptors, CaMKK, AMPK, and RhoA. In the present study, microtubule dynamics were examined in GnRH neurons. Failure of the migration of these cells leads to the neuroendocrine disorder Kallmann Syndrome. Microtubules translocated forward along the leading process shaft during migration, but reversed direction and moved toward the nucleus when migration stalled. Blocking calcium release through IP3 receptors halted migration and induced the same reversal of microtubule translocation, while blocking cortical actin flow prevented microtubules from translocating toward the distal leading process. Super-resolution imaging revealed that microtubule plus-end tips are captured at the actin cortex through calcium-dependent mechanisms. This work shows that cortical actin flow draws the microtubule network forward through calcium-dependent capture in order to promote nucleokinesis, revealing a novel mechanism engaged by migrating neurons to facilitate movement.

  5. Microtubules as mechanical force sensors.

    Science.gov (United States)

    Karafyllidis, Ioannis G; Lagoudas, Dimitris C

    2007-03-01

    Microtubules are polymers of tubulin subunits (dimers) arranged on a hexagonal lattice. Each tubulin dimer comprises two monomers, the alpha-tubulin and beta-tubulin, and can be found in two states. In the first state a mobile negative charge is located into the alpha-tubulin monomer and in the second into the beta-tubulin monomer. Each tubulin dimer is modeled as an electrical dipole coupled to its neighbors by electrostatic forces. The location of the mobile charge in each dimer depends on the location of the charges in the dimer's neighborhood. Mechanical forces that act on the microtubule affect the distances between the dimers and alter the electrostatic potential. Changes in this potential affect the mobile negative charge location in each dimer and the charge distribution in the microtubule. The net effect is that mechanical forces affect the charge distribution in microtubules. We propose to exploit this effect and use microtubules as mechanical force sensors. We model each dimer as a two-state quantum system and, following the quantum computation paradigm, we use discrete quantum random walk on the hexagonal microtubule lattice to determine the charge distribution. Different forces applied on the microtubule are modeled as different coin biases leading to different probability distributions of the quantum walker location, which are directly connected to different charge distributions. Simulation results show that there is a strong indication that microtubules can be used as mechanical force sensors and that they can also detect the force directions and magnitudes.

  6. Utility deregulation and AMR technology

    International Nuclear Information System (INIS)

    Moore, G.

    1991-01-01

    This article reviews the effects of deregulation on other utilities and services and examines how the electric utilities can avoid the worst of these effects and capitalize of the best aspects of competition in achieving marketing excellence. The article presents deregulation as a customer service and underscores the need for utilities to learn to compete aggressively and intelligently and provide additional services available through technology such as automated meter reading

  7. Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

    Directory of Open Access Journals (Sweden)

    Daniele Fanale

    2015-01-01

    Full Text Available Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.

  8. EML proteins in microtubule regulation and human disease.

    Science.gov (United States)

    Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

    2016-10-15

    The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  9. TONNEAU2/FASS Regulates the Geometry of Microtubule Nucleation and Cortical Array Organization in Interphase Arabidopsis Cells[C][W

    Science.gov (United States)

    Kirik, Angela; Ehrhardt, David W.; Kirik, Viktor

    2012-01-01

    Organization of microtubules into ordered arrays involves spatial and temporal regulation of microtubule nucleation. Here, we show that acentrosomal microtubule nucleation in plant cells involves a previously unknown regulatory step that determines the geometry of microtubule nucleation. Dynamic imaging of interphase cortical microtubules revealed that the ratio of branching to in-bundle microtubule nucleation on cortical microtubules is regulated by the Arabidopsis thaliana B′′ subunit of protein phosphatase 2A, which is encoded by the TONNEAU2/FASS (TON2) gene. The probability of nucleation from γ-tubulin complexes localized at the cell cortex was not affected by a loss of TON2 function, suggesting a specific role of TON2 in regulating the nucleation geometry. Both loss of TON2 function and ectopic targeting of TON2 to the plasma membrane resulted in defects in cell shape, suggesting the importance of TON2-mediated regulation of the microtubule cytoskeleton in cell morphogenesis. Loss of TON2 function also resulted in an inability for cortical arrays to reorient in response to light stimulus, suggesting an essential role for TON2 and microtubule branching nucleation in reorganization of microtubule arrays. Our data establish TON2 as a regulator of interphase microtubule nucleation and provide experimental evidence for a novel regulatory step in the process of microtubule-dependent nucleation. PMID:22395485

  10. Wood cell-wall structure requires local 2D-microtubule disassembly by a novel plasma membrane-anchored protein.

    Science.gov (United States)

    Oda, Yoshihisa; Iida, Yuki; Kondo, Yuki; Fukuda, Hiroo

    2010-07-13

    Plant cells have evolved cortical microtubules, in a two-dimensional space beneath the plasma membrane, that regulate patterning of cellulose deposition. Although recent studies have revealed that several microtubule-associated proteins facilitate self-organization of transverse cortical microtubules, it is still unknown how diverse patterns of cortical microtubules are organized in different xylem cells, which are the major components of wood. Using our newly established in vitro xylem cell differentiation system, we found that a novel microtubule end-tracking protein, microtubule depletion domain 1 (MIDD1), was anchored to distinct plasma membrane domains and promoted local microtubule disassembly, resulting in pits on xylem cell walls. The introduction of RNA interference for MIDD1 resulted in the failure of local microtubule depletion and the formation of secondary walls without pits. Conversely, the overexpression of MIDD1 reduced microtubule density. MIDD1 has two coiled-coil domains for the binding to microtubules and for the anchorage to plasma membrane domains, respectively. Combination of the two coils caused end tracking of microtubules during shrinkage and suppressed their rescue events. Our results indicate that MIDD1 integrates spatial information in the plasma membrane with cortical microtubule dynamics for determining xylem cell wall pattern. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. The undertow of deregulation : reregulation

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    Alberta, Ontario and New Brunswick each initiated measures to deregulate their electric power industries in order to remain competitive with lower electricity rates in some U.S. states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity reregulation 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. It 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. 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 3 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

  12. Polyamine sharing between tubulin dimers favours microtubule nucleation and elongation via facilitated diffusion.

    Directory of Open Access Journals (Sweden)

    Alain Mechulam

    2009-01-01

    Full Text Available We suggest for the first time that the action of multivalent cations on microtubule dynamics can result from facilitated diffusion of GTP-tubulin to the microtubule ends. Facilitated diffusion can promote microtubule assembly, because, upon encountering a growing nucleus or the microtubule wall, random GTP-tubulin sliding on their surfaces will increase the probability of association to the target sites (nucleation sites or MT ends. This is an original explanation for understanding the apparent discrepancy between the high rate of microtubule elongation and the low rate of tubulin association at the microtubule ends in the viscous cytoplasm. The mechanism of facilitated diffusion requires an attraction force between two tubulins, which can result from the sharing of multivalent counterions. Natural polyamines (putrescine, spermidine, and spermine are present in all living cells and are potent agents to trigger tubulin self-attraction. By using an analytical model, we analyze the implication of facilitated diffusion mediated by polyamines on nucleation and elongation of microtubules. In vitro experiments using pure tubulin indicate that the promotion of microtubule assembly by polyamines is typical of facilitated diffusion. The results presented here show that polyamines can be of particular importance for the regulation of the microtubule network in vivo and provide the basis for further investigations into the effects of facilitated diffusion on cytoskeleton dynamics.

  13. Synthesis and biological evaluation of structurally simplified noscapine analogues as microtubule binding agents

    Czech Academy of Sciences Publication Activity Database

    Ghaly, P.E.; Churchill, C.D.M.; Abou El-Magd, R.M.; Hájková, Zuzana; Dráber, Pavel; West, F.G.; Tuszyński, J.A.

    2017-01-01

    Roč. 95, č. 6 (2017), s. 649-655 ISSN 0008-4042 R&D Projects: GA ČR GA15-22194S Institutional support: RVO:68378050 Keywords : noscapine * microtubule * tubulin * cytotoxicity * microtubule dynamics * docking Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 1.080, year: 2016

  14. Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module.

    Science.gov (United States)

    Roostalu, Johanna; Cade, Nicholas I; Surrey, Thomas

    2015-11-01

    Spindle assembly and function require precise control of microtubule nucleation and dynamics. The chromatin-driven spindle assembly pathway exerts such control locally in the vicinity of chromosomes. One of the key targets of this pathway is TPX2. The molecular mechanism of how TPX2 stimulates microtubule nucleation is not understood. Using microscopy-based dynamic in vitro reconstitution assays with purified proteins, we find that human TPX2 directly stabilizes growing microtubule ends and stimulates microtubule nucleation by stabilizing early microtubule nucleation intermediates. Human microtubule polymerase chTOG (XMAP215/Msps/Stu2p/Dis1/Alp14 homologue) only weakly promotes nucleation, but acts synergistically with TPX2. Hence, a combination of distinct and complementary activities is sufficient for efficient microtubule formation in vitro. Importins control the efficiency of the microtubule nucleation by selectively blocking the interaction of TPX2 with microtubule nucleation intermediates. This in vitro reconstitution reveals the molecular mechanism of regulated microtubule formation by a minimal nucleation module essential for chromatin-dependent microtubule nucleation in cells.

  15. Environmental impact of electricity deregulation

    International Nuclear Information System (INIS)

    Swisher, Joel N.; McAlpin, Maria C.

    2006-01-01

    Restructuring of electric utilities affects environmental quality primarily through its effect on airborne emissions. We examine emissions from 1993 to 2002 and discuss possible explanatory factors. Annual NOx and SO 2 emissions fell nationally, mostly due to decreases in emission limits driven by state and Federal regulations. CO 2 emissions have increased almost proportionately with increased generation. Generation increased more than it would have, partly due to energy efficiency spending reductions that accompanied deregulation. The fuel mix shifted slightly from coal to gas, offsetting some CO 2 emissions increases and contributing to SO 2 and NOx emissions decreases. While the percentage share of generation from renewable sources remained at about 2%, recent and expected future increases in wind generating capacity promise future emissions reductions. Although deregulation lacks clear environmental advantages, the deregulation process creates an opportunity for implementation of state policies to reduce emissions. Regulated and deregulated states with renewable portfolio standards (RPS) have a higher average percent of generation from renewable sources. Average energy efficiency savings are higher in regulated states, but slightly higher in deregulated states with a system benefits charge (SBC) than in regulated states without a SBC

  16. Deregulation - a source of crisis?

    International Nuclear Information System (INIS)

    Haavardstein, Hilde; Sandsmark, Maria

    2003-01-01

    Since the beginning of the 1990s, deregulation has become widespread in many of the worlds power markets. When it is no longer the authorities, but the players in the market who are deciding on investments in new production capacity, on the basis of business economic estimates of profitability, it is important that the external conditions are worked out such that they provide incentives to investments of the right extent and to the right time. Examples from deregulated markets show that the formulation of such external frames has contributed to a tight power balance

  17. The growth speed of microtubules with XMAP215-coated beads coupled to their ends is increased by tensile force

    Science.gov (United States)

    Trushko, Anastasiya; Schäffer, Erik; Howard, Jonathon

    2013-01-01

    The generation of pulling and pushing forces is one of the important functions of microtubules, which are dynamic and polarized structures. The ends of dynamic microtubules are able to form relatively stable links to cellular structures, so that when a microtubule grows it can exert a pushing force and when it shrinks it can exert a pulling force. Microtubule growth and shrinkage are tightly regulated by microtubule-associated proteins (MAPs) that bind to microtubule ends. Given their localization, MAPs may be exposed to compressive and tensile forces. The effect of such forces on MAP function, however, is poorly understood. Here we show that beads coated with the microtubule polymerizing protein XMAP215, the Xenopus homolog of Dis1 and chTOG, are able to link stably to the plus ends of microtubules, even when the ends are growing or shrinking; at growing ends, the beads increase the polymerization rate. Using optical tweezers, we found that tensile force further increased the microtubule polymerization rate. These results show that physical forces can regulate the activity of MAPs. Furthermore, our results show that XMAP215 can be used as a handle to sense and mechanically manipulate the dynamics of the microtubule tip. PMID:23964126

  18. Deregulation and Macroeconomic Drivers Of Foreign Direct ...

    African Journals Online (AJOL)

    Deregulation and Macroeconomic Drivers Of Foreign Direct Investment In Nigerian Agriculture (1970 -2009): An Econometric Analysis. ... The study showed that foreign exchange and the economic deregulation policy of Nigerian government ...

  19. Energy deregulation: the Vattenfall experience

    International Nuclear Information System (INIS)

    Nyquist, C.E.

    1999-01-01

    In 1992, Sweden prepared itself for deregulation by transforming Vattenfall, the country's main supplier of energy, from a public utility into a limited liability company. Vattenfall was still 100% owned by the state, but began to operate as a commercial entity with a separate board of directors. On January 1, 1996, Sweden and Finland deregulated, and the three Nordic countries - Norway, Sweden and Denmark - became a completely open market. Beginning November 1, 1999, Sweden will introduce simplified metering, bringing competition directly to consumers, which represents the purest and most advanced form of electricity competition, forcing Vattenfall and its peers to fight for the loyalty of customers from the smallest retail household upwards. As a central participant in deregulation, Vattenfall was faced with some major challenges. In essence, Vattenfall had to evolve from a parochial Swedish public utility into a pan-European energy services company. The transition was successful and Vattenfall today represents about 20% of Scandinavia's generation capacity, with operations that are about 1/2 the size of those of Ontario Hydro. Vattenfall had to take a number of steps to get ready for a fully competitive retail market. First it established a market oriented group organization based on three units: Vattenfall Electricity Generation, Vattenfall Energy Market, and Vattenfall Electricity Networks and Services. Second it expanded its relationship with its customers. Third it adjusted to the fact that electricity deregulation led to an immediate generation surplus. The main lessons learned from the experience are summarized

  20. Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth

    NARCIS (Netherlands)

    Sharma, Ashwani; Aher, Amol; Dynes, Nicola J; Frey, Daniel; Katrukha, Eugene A; Jaussi, Rolf; Grigoriev, Ilya; Croisier, Marie; Kammerer, Richard A; Akhmanova, Anna; Gönczy, Pierre; Steinmetz, Michel O

    2016-01-01

    Centrioles are fundamental and evolutionarily conserved microtubule-based organelles whose assembly is characterized by microtubule growth rates that are orders of magnitude slower than those of cytoplasmic microtubules. Several centriolar proteins can interact with tubulin or microtubules, but how

  1. On the nature and shape of tubulin trails: implications on microtubule self-organization.

    Science.gov (United States)

    Glade, Nicolas

    2012-06-01

    Microtubules, major elements of the cell skeleton are, most of the time, well organized in vivo, but they can also show self-organizing behaviors in time and/or space in purified solutions in vitro. Theoretical studies and models based on the concepts of collective dynamics in complex systems, reaction-diffusion processes and emergent phenomena were proposed to explain some of these behaviors. In the particular case of microtubule spatial self-organization, it has been advanced that microtubules could behave like ants, self-organizing by 'talking to each other' by way of hypothetic (because never observed) concentrated chemical trails of tubulin that are expected to be released by their disassembling ends. Deterministic models based on this idea yielded indeed like-looking spatio-temporal self-organizing behaviors. Nevertheless the question remains of whether microscopic tubulin trails produced by individual or bundles of several microtubules are intense enough to allow microtubule self-organization at a macroscopic level. In the present work, by simulating the diffusion of tubulin in microtubule solutions at the microscopic scale, we measure the shape and intensity of tubulin trails and discuss about the assumption of microtubule self-organization due to the production of chemical trails by disassembling microtubules. We show that the tubulin trails produced by individual microtubules or small microtubule arrays are very weak and not elongated even at very high reactive rates. Although the variations of concentration due to such trails are not significant compared to natural fluctuations of the concentration of tubuline in the chemical environment, the study shows that heterogeneities of biochemical composition can form due to microtubule disassembly. They could become significant when produced by numerous microtubule ends located in the same place. Their possible formation could play a role in certain conditions of reaction. In particular, it gives a mesoscopic

  2. Interactive domains in the molecular chaperone human alphaB crystallin modulate microtubule assembly and disassembly.

    Directory of Open Access Journals (Sweden)

    Joy G Ghosh

    2007-06-01

    Full Text Available Small heat shock proteins regulate microtubule assembly during cell proliferation and in response to stress through interactions that are poorly understood.Novel functions for five interactive sequences in the small heat shock protein and molecular chaperone, human alphaB crystallin, were investigated in the assembly/disassembly of microtubules and aggregation of tubulin using synthetic peptides and mutants of human alphaB crystallin.The interactive sequence (113FISREFHR(120 exposed on the surface of alphaB crystallin decreased microtubule assembly by approximately 45%. In contrast, the interactive sequences, (131LTITSSLSSDGV(142 and (156ERTIPITRE(164, corresponding to the beta8 strand and the C-terminal extension respectively, which are involved in complex formation, increased microtubule assembly by approximately 34-45%. The alphaB crystallin peptides, (113FISREFHR(120 and (156ERTIPITRE(164, inhibited microtubule disassembly by approximately 26-36%, and the peptides (113FISREFHR(120 and (131LTITSSLSSDGV(142 decreased the thermal aggregation of tubulin by approximately 42-44%. The (131LTITSSLSSDGV(142 and (156ERTIPITRE(164 peptides were more effective than the widely used anti-cancer drug, Paclitaxel, in modulating tubulinmicrotubule dynamics. Mutagenesis of these interactive sequences in wt human alphaB crystallin confirmed the effects of the alphaB crystallin peptides on microtubule assembly/disassembly and tubulin aggregation. The regulation of microtubule assembly by alphaB crystallin varied over a narrow range of concentrations. The assembly of microtubules was maximal at alphaB crystallin to tubulin molar ratios between 1:4 and 2:1, while molar ratios >2:1 inhibited microtubule assembly.Interactive sequences on the surface of human alphaB crystallin collectively modulate microtubule assembly through a dynamic subunit exchange mechanism that depends on the concentration and ratio of alphaB crystallin to tubulin. These are the first

  3. Dynamics of competitive strategies in de-regulated industries: the case of the electricity industry in France; Dynamique des strategies concurrentielles dans un contexte de liberalisation: le cas de l'industrie electrique en France

    Energy Technology Data Exchange (ETDEWEB)

    Cateura, O

    2007-11-15

    This research work is focused on the competitive dynamics approach and rivalry studies between competitors. It develops theses recent perspectives and particularly multi-market competition (also called multipoint competition) in de-regulated industries (network utilities). Indeed, competitive behaviours in liberalized industries are still badly-known. To conduct this research, we decided to analyze a selection of companies (EDF, Electrabel, Endesa, Enel, Gaz de France, Poweo, Direct Energie..) settled on the French electricity market presently in the course of liberalization (1996 - 2006). This qualitative research, through longitudinal case studies, has been developed thanks to a CIFRE agreement (between the French Ministry of Research and the firm Electrabel France) including action research and participant observation. Using multidimensional strategic sequences, we identified two periods, the first one characterized by a confrontation movement and a second one by mutual forbearance. We argue that after learning the rules of a newly liberalized market (confrontation, diversification, internationalization), competitors rapidly and collectively shift there positions towards a focused European strategy based on the gas-electricity convergence. The development of multi-market competition has conducted to mutual forbearance, which was particularly profitable to the major participants. Integrated strategy (market and non-market) appears as an important driver for legitimizing theses behaviours. (author)

  4. Dynamics of competitive strategies in de-regulated industries: the case of the electricity industry in France; Dynamique des strategies concurrentielles dans un contexte de liberalisation: le cas de l'industrie electrique en France

    Energy Technology Data Exchange (ETDEWEB)

    Cateura, O

    2007-11-15

    This research work is focused on the competitive dynamics approach and rivalry studies between competitors. It develops theses recent perspectives and particularly multi-market competition (also called multipoint competition) in de-regulated industries (network utilities). Indeed, competitive behaviours in liberalized industries are still badly-known. To conduct this research, we decided to analyze a selection of companies (EDF, Electrabel, Endesa, Enel, Gaz de France, Poweo, Direct Energie..) settled on the French electricity market presently in the course of liberalization (1996 - 2006). This qualitative research, through longitudinal case studies, has been developed thanks to a CIFRE agreement (between the French Ministry of Research and the firm Electrabel France) including action research and participant observation. Using multidimensional strategic sequences, we identified two periods, the first one characterized by a confrontation movement and a second one by mutual forbearance. We argue that after learning the rules of a newly liberalized market (confrontation, diversification, internationalization), competitors rapidly and collectively shift there positions towards a focused European strategy based on the gas-electricity convergence. The development of multi-market competition has conducted to mutual forbearance, which was particularly profitable to the major participants. Integrated strategy (market and non-market) appears as an important driver for legitimizing theses behaviours. (author)

  5. Deregulation of Lesotho's maize market

    OpenAIRE

    van Schalkwyk, Herman D.; van Zyl, Johan; Botha, P.W.; Bayley, B.

    1997-01-01

    During the past year, there have been major policy reforms in Lesotho and South Africa with respect to maize pricing and marketing. In Lesotho the impact of deregulation on producers, consumers and government revenues was substantially lower than it should have been, and as a result Lesotho was not able to reap the full benefits of these changes. This is partly because information on the changes to the maize marketing system did not reach the potential beneficiaries of the new system. Free an...

  6. Lowering electricity prices through deregulation

    OpenAIRE

    Thomas Klitgaard; Rekha Reddy

    2000-01-01

    A wave of regulatory reform is now transforming the U.S. electricity industry. As state and federal authorities allow independent power producers to compete with utilities in supplying electricity, consumers are paying close attention to the effects of this change on their energy bills. Although deregulation poses significant structural challenges, the introduction of competitive pressures should ultimately lead to efficiency gains for the industry and cost savings for households and businesses.

  7. Deregulator: Judgment Day for microeconomics

    International Nuclear Information System (INIS)

    Keen, S.

    2004-01-01

    The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

  8. Deregulator: Judgment Day for microeconomics

    Energy Technology Data Exchange (ETDEWEB)

    Keen, S. [University of Western Sydney, Penrith (Australia). School of Economics and Finance

    2004-09-01

    The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

  9. A ROP2-RIC1 pathway fine-tunes microtubule reorganization for salt tolerance in Arabidopsis.

    Science.gov (United States)

    Li, Changjiang; Lu, Hanmei; Li, Wei; Yuan, Ming; Fu, Ying

    2017-07-01

    The reorganization of microtubules induced by salt stress is required for Arabidopsis survival under high salinity conditions. RIC1 is an effector of Rho-related GTPase from plants (ROPs) and a known microtubule-associated protein. In this study, we demonstrated that RIC1 expression decreased with long-term NaCl treatment, and ric1-1 seedlings exhibited a higher survival rate under salt stress. We found that RIC1 reduced the frequency of microtubule transition from shortening to growing status and knockout of RIC1 improved the reassembly of depolymerized microtubules caused by either oryzalin treatment or salt stress. Further investigation showed that constitutively active ROP2 promoted the reassembly of microtubules and the survival of seedlings under salt stress. A rop2-1 ric1-1 double mutant rescued the salt-sensitive phenotype of rop2-1, indicating that ROP2 functions in salt tolerance through RIC1. Although ROP2 did not regulate RIC1 expression upon salt stress, a quick but mild increase of ROP2 activity was induced, led to reduction of RIC1 on microtubules. Collectively, our study reveals an ROP2-RIC1 pathway that fine-tunes microtubule dynamics in response to salt stress in Arabidopsis. This finding not only reveals a new regulatory mechanism for microtubule reorganization under salt stress but also the importance of ROP signalling for salinity tolerance. © 2017 John Wiley & Sons Ltd.

  10. Natural gas and deregulation in the European Market

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The gas market is progressively moving towards new organizations under the effect of deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European Union. Within the framework provided by this overall trend, Cedigaz proposes a study titled 'Natural Gas and Deregulation' in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appears to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed in the European market, for example. The analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Incidentally, it has adapted the terms 'regulated market' to define conventional markets and 'deregulated market' to define markets which have incorporated the principle of Third Party Access (TPA). This is obviously a mere convention, since in both cases, the gas market, a network market, is regulated either by the State or by an independent agency. Also noteworthy is the diversity of the regulation methods for the network markets. While an underlying principle prevails throughout, particularly the introduction of TPA, political and energy considerations alike are liable to condition strongly the final structure of a given market. The apparently comparable British and American experience thus display substantial differences. In other words, one should not imagine a sudden transposition of either case to the European market. The different States preserve considerable leeway to guide market developments in one direction or another. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by

  11. Manipulation and quantification of microtubule lattice integrity

    Directory of Open Access Journals (Sweden)

    Taylor A. Reid

    2017-08-01

    Full Text Available Microtubules are structural polymers that participate in a wide range of cellular functions. The addition and loss of tubulin subunits allows the microtubule to grow and shorten, as well as to develop and repair defects and gaps in its cylindrical lattice. These lattice defects act to modulate the interactions of microtubules with molecular motors and other microtubule-associated proteins. Therefore, tools to control and measure microtubule lattice structure will be invaluable for developing a quantitative understanding of how the structural state of the microtubule lattice may regulate its interactions with other proteins. In this work, we manipulated the lattice integrity of in vitro microtubules to create pools of microtubules with common nucleotide states, but with variations in structural states. We then developed a series of novel semi-automated analysis tools for both fluorescence and electron microscopy experiments to quantify the type and severity of alterations in microtubule lattice integrity. These techniques will enable new investigations that explore the role of microtubule lattice structure in interactions with microtubule-associated proteins.

  12. Dynamics of multiple nuclei in Ashbya gossypii hyphae depend on the control of cytoplasmic microtubules length by Bik1, Kip2, Kip3, and not on a capture/shrinkage mechanism.

    Science.gov (United States)

    Grava, Sandrine; Philippsen, Peter

    2010-11-01

    Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae. In contrast to budding yeast where positioning of nuclei at the bud neck is a major function of cytoplasmic microtubules (cMTs), A. gossypii nuclei are constantly in motion and positioning is not an issue. To investigate the role of cMTs in nuclear oscillation and bypassing, we constructed mutants potentially affecting cMT lengths. Hyphae lacking the plus (+)end marker Bik1 or the kinesin Kip2 cannot polymerize long cMTs and lose wild-type nuclear movements. Interestingly, hyphae lacking the kinesin Kip3 display longer cMTs concomitant with increased nuclear oscillation and bypassing. Polymerization and depolymerization rates of cMTs are 3 times higher in A. gossypii than in budding yeast and cMT catastrophes are rare. Growing cMTs slide along the hyphal cortex and exert pulling forces on nuclei. Surprisingly, a capture/shrinkage mechanism seems to be absent in A. gossypii. cMTs reaching a hyphal tip do not shrink, and cMT +ends accumulate in hyphal tips. Thus, differences in cMT dynamics and length control between budding yeast and A. gossypii are key elements in the adaptation of the cMT cytoskeleton to much longer cells and much higher degrees of nuclear mobilities.

  13. Taking directions: the role of microtubule-bound nucleation in the self-organization of the plant cortical array

    International Nuclear Information System (INIS)

    Deinum, Eva E; Tindemans, Simon H; Mulder, Bela M

    2011-01-01

    The highly aligned cortical microtubule array of interphase plant cells is a key regulator of anisotropic cell expansion. Recent computational and analytical work has shown that the non-equilibrium self-organization of this structure can be understood on the basis of experimentally observed collisional interactions between dynamic microtubules attached to the plasma membrane. Most of these approaches assumed that new microtubules are homogeneously and isotropically nucleated on the cortical surface. Experimental evidence, however, shows that nucleation mostly occurs from other microtubules and under specific relative angles. Here, we investigate the impact of directed microtubule-bound nucleations on the alignment process using computer simulations. The results show that microtubule-bound nucleations can increase the degree of alignment achieved, decrease the timescale of the ordering process and widen the regime of dynamic parameters for which the system can self-organize. We establish that the major determinant of this effect is the degree of co-alignment of the nucleations with the parent microtubule. The specific role of sideways branching nucleations appears to allow stronger alignment while maintaining a measure of overall spatial homogeneity. Finally, we investigate the suggestion that observed persistent rotation of microtubule domains can be explained through a handedness bias in microtubule-bound nucleations, showing that this is possible only for an extreme bias and over a limited range of parameters

  14. Taking directions: the role of microtubule-bound nucleation in the self-organization of the plant cortical array

    Science.gov (United States)

    Deinum, Eva E.; Tindemans, Simon H.; Mulder, Bela M.

    2011-10-01

    The highly aligned cortical microtubule array of interphase plant cells is a key regulator of anisotropic cell expansion. Recent computational and analytical work has shown that the non-equilibrium self-organization of this structure can be understood on the basis of experimentally observed collisional interactions between dynamic microtubules attached to the plasma membrane. Most of these approaches assumed that new microtubules are homogeneously and isotropically nucleated on the cortical surface. Experimental evidence, however, shows that nucleation mostly occurs from other microtubules and under specific relative angles. Here, we investigate the impact of directed microtubule-bound nucleations on the alignment process using computer simulations. The results show that microtubule-bound nucleations can increase the degree of alignment achieved, decrease the timescale of the ordering process and widen the regime of dynamic parameters for which the system can self-organize. We establish that the major determinant of this effect is the degree of co-alignment of the nucleations with the parent microtubule. The specific role of sideways branching nucleations appears to allow stronger alignment while maintaining a measure of overall spatial homogeneity. Finally, we investigate the suggestion that observed persistent rotation of microtubule domains can be explained through a handedness bias in microtubule-bound nucleations, showing that this is possible only for an extreme bias and over a limited range of parameters.

  15. Model for the orientational ordering of the plant microtubule cortical array

    Science.gov (United States)

    Hawkins, Rhoda J.; Tindemans, Simon H.; Mulder, Bela M.

    2010-07-01

    The plant microtubule cortical array is a striking feature of all growing plant cells. It consists of a more or less homogeneously distributed array of highly aligned microtubules connected to the inner side of the plasma membrane and oriented transversely to the cell growth axis. Here, we formulate a continuum model to describe the origin of orientational order in such confined arrays of dynamical microtubules. The model is based on recent experimental observations that show that a growing cortical microtubule can interact through angle dependent collisions with pre-existing microtubules that can lead either to co-alignment of the growth, retraction through catastrophe induction or crossing over the encountered microtubule. We identify a single control parameter, which is fully determined by the nucleation rate and intrinsic dynamics of individual microtubules. We solve the model analytically in the stationary isotropic phase, discuss the limits of stability of this isotropic phase, and explicitly solve for the ordered stationary states in a simplified version of the model.

  16. Long-term consequences of selected competitive strategies during deregulation of the United States electric utility industry: System dynamics modeling and simulation

    Science.gov (United States)

    Khalil, Yehia Fahim

    Currently, U.S. investor-owned utilities (IOUs) are facing major reforms in their business environment similar to the airlines, telecommunications, banking, and insurance industries. As a result, IOUs are gearing up for fierce price competition in the power generation sector, and are vying for electricity customers outside their franchised service territories. Energy experts predict that some IOUs may suffer fatal financial setbacks (especially those with nuclear plants), while others may thrive under competition. Both federal and state energy regulators anticipate that it may take from five to ten years to complete the transition of America's electric utility industry from a regulated monopoly to a market-driven business. During this transition, utility executives are pursuing aggressive business strategies to confront the upcoming price wars. The most compelling strategies focus on cutting operation and maintenance (O&M) costs of power production, downsizing the work force, and signing bilateral energy agreements with large price-sensitive customers to retain their business. This research assesses the impact of the three pivotal strategies on financial performance of utilities during transition to open market competition. A system-dynamics-based management flight simulator has been developed to predict the dynamic performance of a hypothetical IOU organization preparing for market competition. The simulation results show that while the three business strategies lead to short-lived gains, they also produce unanticipated long-term consequences that adversely impact the organization's operating revenues. Generally, the designed flight simulator serves as a learning laboratory which allows management to test new strategies before implementation.

  17. Did Globalization Influence Credit Market Deregulation

    OpenAIRE

    Eppinger, Peter; Potrafke, Niklas

    2015-01-01

    We investigate whether globalization influenced credit market deregulation over the period 1970-2010. Globalization is measured by the KOF indices of globalization. Credit market deregulation is measured by the credit market freedom indicators of the Fraser Institute. The results from both cross-sectional and panel regressions using ordinary least squares indicate a positive correlation between globalization and credit market deregulation. We account for reverse causality by using predicted t...

  18. Product Market Deregulation and Employment Outcomes

    OpenAIRE

    Senftleben-König, Charlotte

    2014-01-01

    This paper investigates the short- and medium-term effects of the deregulation of shopopening hours legislation on retail employment in Germany. In 2006, the legislative competence was shifted from the federal to the state level, leading to a gradual deregulation of shop opening restrictions in most of Germany’s sixteen federal states. The paper exploits regional variation in the legislation in order to identify the effect product market deregulation has on retail employment. We find robust e...

  19. Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy.

    Science.gov (United States)

    Yan, Si; Guo, Changmiao; Hou, Guangjin; Zhang, Huilan; Lu, Xingyu; Williams, John Charles; Polenova, Tatyana

    2015-11-24

    Microtubules and their associated proteins perform a broad array of essential physiological functions, including mitosis, polarization and differentiation, cell migration, and vesicle and organelle transport. As such, they have been extensively studied at multiple levels of resolution (e.g., from structural biology to cell biology). Despite these efforts, there remain significant gaps in our knowledge concerning how microtubule-binding proteins bind to microtubules, how dynamics connect different conformational states, and how these interactions and dynamics affect cellular processes. Structures of microtubule-associated proteins assembled on polymeric microtubules are not known at atomic resolution. Here, we report a structure of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of dynactin motor on polymeric microtubules, solved by magic angle spinning NMR spectroscopy. We present the intermolecular interface of CAP-Gly with microtubules, derived by recording direct dipolar contacts between CAP-Gly and tubulin using double rotational echo double resonance (dREDOR)-filtered experiments. Our results indicate that the structure adopted by CAP-Gly varies, particularly around its loop regions, permitting its interaction with multiple binding partners and with the microtubules. To our knowledge, this study reports the first atomic-resolution structure of a microtubule-associated protein on polymeric microtubules. Our approach lays the foundation for atomic-resolution structural analysis of other microtubule-associated motors.

  20. Deregulation, a challenge for regulators

    International Nuclear Information System (INIS)

    Alonso, Augustin

    2001-01-01

    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

  1. Deregulation impacts AMR business cases

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, M.; Fauth, G.

    2001-09-01

    Meter reading strategy is being affected in fundamental ways by deregulation. For the utilities attempting to cope with meter reading unbundling, the processes, insights and general rules that had been developed prior to 2000 in the field of Automatic Meter Reading can no longer be relied upon to provide useful lessons. The fundamental impact on Automatic Meter Reading (AMR) business case drivers and the increasing complexity of building the business case model result from deregulation and unbundling. More and more, management has come to rely on rigorous business case analysis to compensate for the magnitude of AMR projects on the utility and the scarcity of financial resources. One can now expect the Chief Financial Officer and the Vice President Finance to become active players on AMR project teams in the fields of business case scrutiny and approval. Increasingly, the normal expertise of AMR personnel does not suffice to build a business case acceptable to finance. The financial and economic analysis skills required are ever more complex.

  2. Structural differences between yeast and mammalian microtubules revealed by cryo-EM

    Energy Technology Data Exchange (ETDEWEB)

    Howes, Stuart C. [Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group; Geyer, Elisabeth A. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; LaFrance, Benjamin [Univ. of California, Berkeley, CA (United States). Molecular and Cell Biology Graduate Program; Zhang, Rui [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Kellogg, Elizabeth H. [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Westermann, Stefan [Univ. of Duisburg-Essen, Essen (Germany). Dept. of Molecular Genetics, Center for Medical Biotechnology; Rice, Luke M. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; Nogales, Eva [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Molecular Biology and California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

    2017-06-26

    Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction might reflect slower GTP hydrolysis or a different degree of allosteric coupling in the lattice. The microtubule plus end–tracking protein Bim1 binds yeast microtubules both between αβ-tubulin heterodimers, as seen for other organisms, and within tubulin dimers, but binds mammalian tubulin only at interdimer contacts. At the concentrations used in cryo-electron microscopy, Bim1 causes the compaction of yeast microtubules and induces their rapid disassembly. In conclusion, our studies demonstrate structural differences between yeast and mammalian microtubules that likely underlie their differing polymerization dynamics. These differences may reflect adaptations to the demands of different cell size or range of physiological growth temperatures.

  3. Microtubule nucleation and organization in dendrites

    Science.gov (United States)

    Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

    2016-01-01

    ABSTRACT Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

  4. Power Buying: Planning For Your Deregulated Future.

    Science.gov (United States)

    Robertson, Wayne K.

    1997-01-01

    Colleges and universities can benefit from the coming deregulation of utilities. Deregulation creates opportunity for facility managers to aggressively negotiate agreements, implement changes to the physical plant to make the institution a more attractive customer, and explore new, less expensive energy supply options and alternatives. Some action…

  5. Economic and Environmental Effects of Airline Deregulation

    NARCIS (Netherlands)

    Schipper, Youdi; Rietveld, Piet

    1997-01-01

    This paper deals with the issue of regulatory reform in the airline industry, in connection with environmental externalities. Deregulation has led to shorter routes, higher frequencies, probably larger aircraft sizes and more intense peak traffic at airports. In addition, deregulation has led to

  6. Deregulation: Implications for Community College Leaders.

    Science.gov (United States)

    Bender, Louis W.

    1986-01-01

    Looks at the ways in which the deregulation of business and industry may affect community colleges in the years ahead, using the banking industry as an illustration. Argues that the deregulation of higher education requires that community college leadership programs examine past assumptions and develop new strategies. (LAL)

  7. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

    Directory of Open Access Journals (Sweden)

    Coralie Fassier

    2013-01-01

    Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP, a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.

  8. The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

    Science.gov (United States)

    Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

    2013-01-01

    Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs. PMID:23593258

  9. The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs.

  10. The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

    Science.gov (United States)

    Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

    2013-01-01

    Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs.

  11. GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe.

    Science.gov (United States)

    Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S; Geyer, Elisabeth A; Burns, Alexander; Ye, Xuecheng; Rice, Luke M

    2016-11-07

    Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe-the switch from growing to shrinking-occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. © 2016 Piedra et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Dissecting the nanoscale distributions and functions of microtubule-end-binding proteins EB1 and ch-TOG in interphase HeLa cells.

    Directory of Open Access Journals (Sweden)

    Satoko Nakamura

    Full Text Available Recently, the EB1 and XMAP215/TOG families of microtubule binding proteins have been demonstrated to bind autonomously to the growing plus ends of microtubules and regulate their behaviour in in vitro systems. However, their functional redundancy or difference in cells remains obscure. Here, we compared the nanoscale distributions of EB1 and ch-TOG along microtubules using high-resolution microscopy techniques, and also their roles in microtubule organisation in interphase HeLa cells. The ch-TOG accumulation sites protruded ∼100 nm from the EB1 comets. Overexpression experiments showed that ch-TOG and EB1 did not interfere with each other's localisation, confirming that they recognise distinct regions at the ends of microtubules. While both EB1 and ch-TOG showed similar effects on microtubule plus end dynamics and additively increased microtubule dynamicity, only EB1 exhibited microtubule-cell cortex attachment activity. These observations indicate that EB1 and ch-TOG regulate microtubule organisation differently via distinct regions in the plus ends of microtubules.

  13. Katanin: A Sword Cutting Microtubules for Cellular, Developmental, and Physiological Purposes

    Directory of Open Access Journals (Sweden)

    Ivan Luptovčiak

    2017-11-01

    Full Text Available KATANIN is a well-studied microtubule severing protein affecting microtubule organization and dynamic properties in higher plants. By regulating mitotic and cytokinetic and cortical microtubule arrays it is involved in the progression of cell division and cell division plane orientation. KATANIN is also involved in cell elongation and morphogenesis during plant growth. In this way KATANIN plays critical roles in diverse plant developmental processes including the development of pollen, embryo, seed, meristem, root, hypocotyl, cotyledon, leaf, shoot, and silique. KATANIN-dependent microtubule regulation seems to be under the control of plant hormones. This minireview provides an overview on available KATANIN mutants and discusses advances in our understanding of KATANIN biological roles in plants.

  14. C-terminal region of MAP7 domain containing protein 3 (MAP7D3 promotes microtubule polymerization by binding at the C-terminal tail of tubulin.

    Directory of Open Access Journals (Sweden)

    Saroj Yadav

    Full Text Available MAP7 domain containing protein 3 (MAP7D3, a newly identified microtubule associated protein, has been shown to promote microtubule assembly and stability. Its microtubule binding region has been reported to consist of two coiled coil motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus and belongs to the microtubule associated protein 7 (MAP7 family. The MAP7 domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to microtubules as well as enhanced the assembly of microtubules in vitro. Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD with the C-terminal tail (CT of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. MDCT stabilized microtubules against dilution induced disassembly. MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0 ± 0.5 µM. An immunostaining experiment showed that MDCT localized along the length of the preassembled microtubules. Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. Further, we present evidence indicating that MDCT binds to the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa cell extract. Here, we report a microtubule binding region in the C-terminal region of MAP7D3 that may have a role in regulating microtubule assembly dynamics.

  15. Tubulin cofactor B regulates microtubule densities during microglia transition to the reactive states

    International Nuclear Information System (INIS)

    Fanarraga, M.L.; Villegas, J.C.; Carranza, G.; Castano, R.; Zabala, J.C.

    2009-01-01

    Microglia are highly dynamic cells of the CNS that continuously survey the welfare of the neural parenchyma and play key roles modulating neurogenesis and neuronal cell death. In response to injury or pathogen invasion parenchymal microglia transforms into a more active cell that proliferates, migrates and behaves as a macrophage. The acquisition of these extra skills implicates enormous modifications of the microtubule and actin cytoskeletons. Here we show that tubulin cofactor B (TBCB), which has been found to contribute to various aspects of microtubule dynamics in vivo, is also implicated in microglial cytoskeletal changes. We find that TBCB is upregulated in post-lesion reactive parenchymal microglia/macrophages, in interferon treated BV-2 microglial cells, and in neonate amoeboid microglia where the microtubule densities are remarkably low. Our data demonstrate that upon TBCB downregulation both, after microglia differentiation to the ramified phenotype in vivo and in vitro, or after TBCB gene silencing, microtubule densities are restored in these cells. Taken together these observations support the view that TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into the understanding of the complex mechanisms controlling microtubule reorganization during microglial transition between the amoeboid, ramified, and reactive phenotypes

  16. Effects of the Deregulation on the Concentration of the Brazilian Air Transportation Industry

    Science.gov (United States)

    Guterres, Marcelo Xavier; Muller, Carlos

    2003-01-01

    This paper addresses the effects of the deregulation of the Brazilian air transportation industry in terms of the concentration of the market. We will show some metrics that are commonly used to study the concentration of the industry. This paper uses the Herfindhal- Hirschman Index. This index tends to zero in the competitive scenario, with a large number of small firms, and to one in case of a monopolistic scenario. The paper analyses the dynamics of the concentration of the Brazilian domestic air transportation market, in order to evaluate the effects of deregulation. We conclude that the Brazilian market presents oligopoly characteristics and aspects in its current structure that maintain the market concentrated in spite of the Deregulation measures adopted by the aeronautical authority. Keywords: Herfindhal-Hirschman Index, concentration, Deregulation

  17. Microtubule bundling plays a role in ethylene-mediated cortical microtubule reorientation in etiolated Arabidopsis hypocotyls.

    Science.gov (United States)

    Ma, Qianqian; Sun, Jingbo; Mao, Tonglin

    2016-05-15

    The gaseous hormone ethylene is known to regulate plant growth under etiolated conditions (the 'triple response'). Although organization of cortical microtubules is essential for cell elongation, the underlying mechanisms that regulate microtubule organization by hormone signaling, including ethylene, are ambiguous. In the present study, we demonstrate that ethylene signaling participates in regulation of cortical microtubule reorientation. In particular, regulation of microtubule bundling is important for this process in etiolated hypocotyls. Time-lapse analysis indicated that selective stabilization of microtubule-bundling structures formed in various arrays is related to ethylene-mediated microtubule orientation. Bundling events and bundle growth lifetimes were significantly increased in oblique and longitudinal arrays, but decreased in transverse arrays in wild-type cells in response to ethylene. However, the effects of ethylene on microtubule bundling were partially suppressed in a microtubule-bundling protein WDL5 knockout mutant (wdl5-1). This study suggests that modulation of microtubule bundles that have formed in certain orientations plays a role in reorienting microtubule arrays in response to ethylene-mediated etiolated hypocotyl cell elongation. © 2016. Published by The Company of Biologists Ltd.

  18. Energy deregulation: lessons from the American experience

    International Nuclear Information System (INIS)

    Chiam, L.

    1997-01-01

    This article presents a brief history of US energy regulation, considers some of the important issues arising from the US experience and finally, suggests some lessons which Australia might draw from the US deregulation of energy industries. 5 refs

  19. Power system deregulation and the Balkan countries

    International Nuclear Information System (INIS)

    Glamochanin, Vlastimir; Stojkovska, Biljana; Cherepnalkoski, Trajche

    2001-01-01

    The aim of the paper is to show the current state and planned activities of the Power System deregulation and privatization in the following Balkan countries: Macedonia, Romania, Bulgaria, Yugoslavia, Greece, Croatia, Slovenia and Turkey

  20. Banking deregulation and corporate tax avoidance

    Directory of Open Access Journals (Sweden)

    Bill B. Francis

    2017-06-01

    Full Text Available We investigate whether tax avoidance substitutes for external financing. We exploit interstate banking deregulation as a quasi-external shock to examine whether firms engage in less tax avoidance after banking deregulation, because of cheaper and easier access to credit from banks. We find no empirical evidence to support this substitutive relation, even for firms with higher financial constraints or firms with higher external financing dependence.

  1. Implications of U.S. electricity deregulation

    International Nuclear Information System (INIS)

    Gottfried, D.A.

    1997-01-01

    This article is a concise summary of the potential impacts of electric utility deregulation, including the resolution of stranded costs, impact on electricity rates, reformation of utilities, and reshuffling of the nation's fuel portfolio. The national and state implications of the deregulation of the electricity industry are monumental and overwhelming. The implications occur on many fronts, including monetary, quality, reliability, and environmental issues. Many significant changes will occur as a result--some will be positive and others may be more disturbing

  2. Direct evidence for GTP and GDP-Pi intermediates in microtubule assembly

    International Nuclear Information System (INIS)

    Melki, R.; Carlier, M.F.; Pantaloni, D.

    1990-01-01

    Identification of the kinetic intermediates in GTP hydrolysis on microtubules and characterization of their assembly properties is essential in understanding microtubule dynamics. By using an improved glass filter assay that selectively traps microtubules with a dead time of 2 s and monitoring taxol-induced rapid assembly of microtubules from [γ- 32 P, 3 H]GTP-tubulin 1:1 complex, direct evidence has been obtained for GTP- and GDP-P i -microtubule transient states in the early stages of the polymerization process. A simple kinetic analysis of GTP hydrolysis on microtubules within two sequential pseudo-first-order processes led to apparent first-order rate constants of 0.065 s -1 for the cleavage of the γ-phosphate and 0.02 s -1 for the liberation of P i , assuming a simple random model. Apparent rate constants for GTP hydrolysis and P i release were independent of the composition of the buffer used to polymerize tubulin. The significance of these values with respect to those derived from previous studies from this and other laboratories and the possibility of a vectorial model for GTP hydrolysis are discussed

  3. Generation capacity expansion planning in deregulated electricity markets

    Science.gov (United States)

    Sharma, Deepak

    With increasing demand of electric power in the context of deregulated electricity markets, a good strategic planning for the growth of the power system is critical for our tomorrow. There is a need to build new resources in the form of generation plants and transmission lines while considering the effects of these new resources on power system operations, market economics and the long-term dynamics of the economy. In deregulation, the exercise of generation planning has undergone a paradigm shift. The first stage of generation planning is now undertaken by the individual investors. These investors see investments in generation capacity as an increasing business opportunity because of the increasing market prices. Therefore, the main objective of such a planning exercise, carried out by individual investors, is typically that of long-term profit maximization. This thesis presents some modeling frameworks for generation capacity expansion planning applicable to independent investor firms in the context of power industry deregulation. These modeling frameworks include various technical and financing issues within the process of power system planning. The proposed modeling frameworks consider the long-term decision making process of investor firms, the discrete nature of generation capacity addition and incorporates transmission network modeling. Studies have been carried out to examine the impact of the optimal investment plans on transmission network loadings in the long-run by integrating the generation capacity expansion planning framework within a modified IEEE 30-bus transmission system network. The work assesses the importance of arriving at an optimal IRR at which the firm's profit maximization objective attains an extremum value. The mathematical model is further improved to incorporate binary variables while considering discrete unit sizes, and subsequently to include the detailed transmission network representation. The proposed models are novel in the

  4. Moonlighting microtubule-associated proteins: regulatory functions by day and pathological functions at night.

    Science.gov (United States)

    Oláh, J; Tőkési, N; Lehotzky, A; Orosz, F; Ovádi, J

    2013-11-01

    The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeletal network. Cytoskeleton comprises fibrous protein networks of microtubules, actin, and intermediate filaments. These filamentous polymer structures are highly dynamic and undergo constant and rapid reorganization during cellular processes. The microtubular system plays a crucial role in the brain, as it is involved in an enormous number of cellular events including cell differentiation and pathological inclusion formation. These multifarious functions of microtubules can be achieved by their decoration with proteins/enzymes that exert specific effects on the dynamics and organization of the cytoskeleton and mediate distinct functions due to their moonlighting features. This mini-review focuses on two aspects of the microtubule cytoskeleton. On the one hand, we describe the heteroassociation of tubulin/microtubules with metabolic enzymes, which in addition to their catalytic activities stabilize microtubule structures via their cross-linking functions. On the other hand, we focus on the recently identified moonlighting tubulin polymerization promoting protein, TPPP/p25. TPPP/p25 is a microtubule-associated protein and it displays distinct physiological or pathological (aberrant) functions; thus it is a prototype of Neomorphic Moonlighting Proteins. The expression of TPPP/p25 is finely controlled in the human brain; this protein is indispensable for the development of projections of oligodendrocytes that are responsible for the ensheathment of axons. The nonphysiological, higher or lower TPPP/p25 level leads to distinct CNS diseases. Mechanisms contributing to the control of microtubule stability and dynamics by metabolic enzymes and TPPP/p25 will be discussed. Copyright © 2013 Wiley Periodicals, Inc.

  5. Profilin connects actin assembly with microtubule dynamics

    Czech Academy of Sciences Publication Activity Database

    Nejedla, M.; Sadi, S.; Sulimenko, Vadym; de Almeida, F.N.; Blom, H.; Dráber, Pavel; Aspenstrom, P.; Karlsson, R.

    2016-01-01

    Roč. 27, č. 15 (2016), s. 2381-2393 ISSN 1059-1524 R&D Projects: GA ČR GA16-25159S Institutional support: RVO:68378050 Keywords : cross-linked profilin * arp2/3 complex * f-actin * microfilament system * migrating cells * focal adhesions * cultured-cells * messenger-rna * living cells * protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.685, year: 2016

  6. A novel mechanism important for the alignment of microtubules.

    Science.gov (United States)

    Wightman, Raymond; Turner, Simon R

    2008-04-01

    Using a live-cell imaging approach to study individual micro-tubules, we have compared microtubule behavior between net-like and aligned cortical arrays. In contrast to previous studies, a steep angled collision between the growing end of a microtubule and a preexisting microtubule was found to favor crossover. Frequencies of microtubule crossovers, bundling and catastrophes are similar regardless of whether the cell exhibited a net-like or aligned microtubule array. In the predominantly aligned array of petiole cells, severing occurs at the sites of microtubule crossovers and serves to remove unaligned microtubules and to increase microtubule density. Severing was observed to be rare in net-like arrays. Microtubule severing is carried out by the katanin enzyme. In this addendum, we present new insights into the possible mechanism of crossing over and preliminary data looking at organization of the array in a katanin mutant.

  7. Consequences of electricity deregulation on nuclear safety

    International Nuclear Information System (INIS)

    Podjavorsek, M.

    2007-01-01

    The evolution of deregulation of electricity market started a couple of years ago and has not been finished yet. Deregulation causes increased pressure to reduce the costs of electricity generation. This presents a new challenge to regulatory bodies. They have to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the deregulation. Today's trend is that the number of electricity generating power companies will be reduced in Europe and also in Slovenia due to tough competition in the electricity market. The electricity price has decreased after the introduction of the deregulated market in most countries. This has been also the main reason for less investment to new generating capacities since the price has been lower than the generation costs. Investment problems are also present for the existing units, because of danger of inappropriate maintenance and reduction of the number of staff and their qualifications below the desired level that leads to loss of institutional memory. It is expected that only the biggest companies can stand the consequences of competition in electricity prices and consequential pressure to reduce the cost. In order to review the impact of deregulation of the electricity market some relevant points are discussed in this paper such as the need to cut costs of companies by reducing the number of their activities and increasing the efficiency in the remaining activities and /or outsourcing of activities, power station operating regime, safety culture, grid reliability, reliability and safety of operation, increased number of transients, ageing of components, outage duration, extended cycle and response of nuclear regulators. From a regulatory point of view the impact of deregulation on nuclear safety is an important issue. This paper also discusses analyses and evaluations of this impact and proposes some measures how to

  8. Microtubule array reorientation in response to hormones does not involve changes in microtubule nucleation modes at the periclinal cell surface

    Science.gov (United States)

    Atkinson, Samantha; Kirik, Angela; Kirik, Viktor

    2014-01-01

    Aligned microtubule arrays spatially organize cell division, trafficking, and determine the direction of cell expansion in plant cells. In response to changes in environmental and developmental signals, cells reorganize their microtubule arrays into new configurations. Here, we tested the role of microtubule nucleation during hormone-induced microtubule array reorientation. We have found that in the process of microtubule array reorientation the ratios between branching, parallel, and de-novo nucleations remained constant, suggesting that the microtubule reorientation mechanism does not involve changes in nucleation modes. In the ton2/fass mutant, which has reduced microtubule branching nucleation frequency and decreased nucleation activity of the γ-tubulin complexes, microtubule arrays were able to reorient. Presented data suggest that reorientation of microtubules into transverse arrays in response to hormones does not involve changes in microtubule nucleation at the periclinal cell surface PMID:25135522

  9. Deregulated power prices: comparison of diurnal patterns

    International Nuclear Information System (INIS)

    Ying Li; Flynn, P.C.

    2004-01-01

    We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms. (Author)

  10. Deregulated power prices: comparison of diurnal patterns

    International Nuclear Information System (INIS)

    Li Ying; Flynn, Peter C.

    2004-01-01

    We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms

  11. Identification and characterization of SSE15206, a microtubule depolymerizing agent that overcomes multidrug resistance

    KAUST Repository

    Manzoor, Safia

    2018-02-13

    Microtubules are highly dynamic structures that form spindle fibres during mitosis and are one of the most validated cancer targets. The success of drugs targeting microtubules, however, is often limited by the development of multidrug resistance. Here we describe the discovery and characterization of SSE15206, a pyrazolinethioamide derivative [3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide] that has potent antiproliferative activities in cancer cell lines of different origins and overcomes resistance to microtubule-targeting agents. Treatment of cells with SSE15206 causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation, a phenotype often associated with drugs that interfere with microtubule dynamics. SSE15206 inhibits microtubule polymerization both in biochemical and cellular assays by binding to colchicine site in tubulin as shown by docking and competition studies. Prolonged treatment of cells with the compound results in apoptotic cell death [increased Poly (ADP-ribose) polymerase cleavage and Annexin V/PI staining] accompanied by p53 induction. More importantly, we demonstrate that SSE15206 is able to overcome resistance to chemotherapeutic drugs in different cancer cell lines including multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1, making it a promising hit for the lead optimization studies to target multidrug resistance.

  12. Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J.; Anderson, Charles T.

    2015-11-02

    Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis.

  13. TIPsy tour guides: How microtubule plus-end tracking proteins (+TIPs facilitate axon guidance

    Directory of Open Access Journals (Sweden)

    Elizabeth A Bearce

    2015-06-01

    Full Text Available The growth cone is a dynamic cytoskeletal vehicle, which drives the end of a developing axon. It serves to interpret and navigate through the complex landscape and guidance cues of the early nervous system. The growth cone’s distinctive cytoskeletal organization offers a fascinating platform to study how extracellular cues can be translated into mechanical outgrowth and turning behaviors. While many studies of cell motility highlight the importance of actin networks in signaling, adhesion, and propulsion, both seminal and emerging works in the field have highlighted a unique and necessary role for microtubules in growth cone navigation. Here, we focus on the role of singular pioneer microtubules, which extend into the growth cone periphery and are regulated by a diverse family of microtubule plus-end tracking proteins (+TIPs. These +TIPs accumulate at the dynamic ends of microtubules, where they are well-positioned to encounter and respond to key signaling events downstream of guidance receptors, catalyzing immediate changes in microtubule stability and actin cross-talk, that facilitate both axonal outgrowth and turning events.

  14. Transmission planning in a deregulated environment

    DEFF Research Database (Denmark)

    Xu, Zhao

    2006-01-01

    The worldwide trend for the deregulation of the electricity generation and transmission industries has led to dramatic changes in system operation and planning procedures. The optimum approach to transmission-expansion planning in a deregulated environment is an open problem especially when the r...... electricity market grid are performed. In addition, the proposed method is compared with a traditional planning method to further verify its effectiveness....... the responsibilities of the organisations carrying out the planning work need to be addressed. To date there is a consensus that the system operator and network manager perform the expansion planning work in a centralised way. However, with an increasing input from the electricity market, the objectives, constraints...... and approaches toward transmission planning should be carefully designed to ensure system reliability as well as meeting the market requirements. A market-oriented approach for transmission planning in a deregulated environment is proposed. Case studies using the IEEE 14-bus system and the Australian national...

  15. Interaction of the Tobacco mosaic virus movement protein with microtubules during the cell cycle in tobacco BY-2 cells.

    Science.gov (United States)

    Boutant, Emmanuel; Fitterer, Chantal; Ritzenthaler, Christophe; Heinlein, Manfred

    2009-10-01

    Cell-to-cell movement of Tobacco mosaic virus (TMV) involves the interaction of virus-encoded 30-kDa movement protein (MP) with microtubules. In cells behind the infection front that accumulate high levels of MP, this activity is reflected by the formation of stabilized MP/microtubule complexes. The ability of MP to bind along and stabilize microtubules is conserved upon expression in mammalian cells. In mammalian cells, the protein also leads to inhibition of mitosis and cell division through a microtubule-independent process correlated with the loss of centrosomal gamma-tubulin and of centrosomal microtubule-nucleation activity. Since MP has the capacity to interact with plant factors involved in microtubule nucleation and dynamics, we used inducible expression in BY-2 cells to test whether MP expression inhibits mitosis and cell division also in plants. We demonstrate that MP:GFP associates with all plant microtubule arrays and, unlike in mammalian cells, does not interfere with mitosis. Thus, MP function and the interaction of MP with factors of the cytoskeleton do not entail an inhibition of mitosis in plants. We also report that the protein targets primary plasmodesmata in BY-2 cells immediately upon or during cytokinesis and that the accumulation of MP in plasmodesmata occurs in the presence of inhibitors of the cytoskeleton and the secretory pathway.

  16. Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

    Science.gov (United States)

    Zhu, Jie; Burakov, Anton; Rodionov, Vladimir

    2010-01-01

    The centrosome position in many types of interphase cells is actively maintained in the cell center. Our previous work indicated that the centrosome is kept at the center by pulling force generated by dynein and actin flow produced by myosin contraction and that an unidentified factor that depends on microtubule dynamics destabilizes position of the centrosome. Here, we use modeling to simulate the centrosome positioning based on the idea that the balance of three forces—dyneins pulling along microtubule length, myosin-powered centripetal drag, and microtubules pushing on organelles—is responsible for the centrosome displacement. By comparing numerical predictions with centrosome behavior in wild-type and perturbed interphase cells, we rule out several plausible hypotheses about the nature of the microtubule-based force. We conclude that strong dynein- and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center. The model also predicts that kinesin action could be another outward-pushing force. Simulations demonstrate that the force-balance centering mechanism is robust yet versatile. We use the experimental observations to reverse engineer the characteristic forces and centrosome mobility. PMID:20980619

  17. Electricity deregulation roundup : Ontario prepares for electricity deregulation and anxiously watches impact elsewhere

    International Nuclear Information System (INIS)

    Hurst, R.

    2000-01-01

    As the time for deregulation of Ontario's electric power industry approaches, consumers are watching other Canadian and American jurisdictions to see what deregulation will mean in terms of energy costs. Albertans have expressed serious concerns about the impact of deregulating their electric power industry. They found that in the four years since deregulation in their province, electricity prices increased when markets opened to competition. The proposed start date for deregulation in Ontario is November 1, 2000. This paper suggests that if investors don't put out significant resources, problems such as power shortages and brownouts could occur, as was the case in Alberta. Potential investors in the Ontario electricity market are already sceptical because the Ontario government, in an effort to protect consumers from unreasonable price increases, has tabled legislation that restricts the efforts of municipal utility companies to raise distribution rates. One step that will inspire some confidence is the recently finalized deal between Ontario Power Generation and British Energy to operate the Bruce Nuclear Power Station. Independent consultants have warned that electricity prices will continue to increase with deregulation for a least the next few years. Industrial customers will be the hardest hit. In California, America's first deregulated electricity market, the power grid is strained and prices have doubled or tripled in one year

  18. Deregulation of Interferon Signaling in Malignant Cells

    Directory of Open Access Journals (Sweden)

    Leonidas C. Platanias

    2010-02-01

    Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

  19. A law enforcement perspective of electricity deregulation

    International Nuclear Information System (INIS)

    Horowitz, Ira

    2006-01-01

    In April 2004, the California Attorney General's (AG) office issued a white paper that provided a 'law enforcement perspective of the California energy crisis.' To complete this special issue's coverage, I summarize three aspects of that paper: notably, the deficiencies in market oversight and enforcement that left the deregulated market prone to potential abuse, the principal modus operandi that some market agents used to exploit those deficiencies without fear of retribution, and the AG's 'recommendations for improving enforcement and protecting consumers in deregulated energy markets.'. (author)

  20. A law enforcement perspective of electricity deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Horowitz, Ira [Warrington College of Business, University of Florida, Gainesville, FL 32611-7169 (United States)

    2006-05-15

    In April 2004, the California Attorney General's (AG) office issued a white paper that provided a 'law enforcement perspective of the California energy crisis.' To complete this special issue's coverage, I summarize three aspects of that paper: notably, the deficiencies in market oversight and enforcement that left the deregulated market prone to potential abuse, the principal modus operandi that some market agents used to exploit those deficiencies without fear of retribution, and the AG's 'recommendations for improving enforcement and protecting consumers in deregulated energy markets.'. (author)

  1. Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

    Science.gov (United States)

    Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

    2011-01-01

    Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

  2. Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

    Directory of Open Access Journals (Sweden)

    Ashley A. Kowalewski

    2011-01-01

    Full Text Available Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22(q24;q12. This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

  3. YB-1 promotes microtubule assembly in vitro through interaction with tubulin and microtubules

    Directory of Open Access Journals (Sweden)

    Baconnais Sonia

    2008-09-01

    Full Text Available Abstract Background YB-1 is a major regulator of gene expression in eukaryotic cells. In addition to its role in transcription, YB-1 plays a key role in translation and stabilization of mRNAs. Results We show here that YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly in vitro. High resolution imaging via electron and atomic force microscopy revealed that microtubules assembled in the presence of YB-1 exhibited a normal single wall ultrastructure and indicated that YB-1 most probably coats the outer microtubule wall. Furthermore, we found that YB-1 also promotes the assembly of MAPs-tubulin and subtilisin-treated tubulin. Finally, we demonstrated that tubulin interferes with RNA:YB-1 complexes. Conclusion These results suggest that YB-1 may regulate microtubule assembly in vivo and that its interaction with tubulin may contribute to the control of mRNA translation.

  4. Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization

    Directory of Open Access Journals (Sweden)

    Jia Shen

    2017-07-01

    Full Text Available Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.

  5. Ferritin associates with marginal band microtubules

    International Nuclear Information System (INIS)

    Infante, Anthony A.; Infante, Dzintra; Chan, M.-C.; How, P.-C.; Kutschera, Waltraud; Linhartova, Irena; Muellner, Ernst W.; Wiche, Gerhard; Propst, Friedrich

    2007-01-01

    We characterized chicken erythrocyte and human platelet ferritin by biochemical studies and immunofluorescence. Erythrocyte ferritin was found to be a homopolymer of H-ferritin subunits, resistant to proteinase K digestion, heat stable, and contained iron. In mature chicken erythrocytes and human platelets, ferritin was localized at the marginal band, a ring-shaped peripheral microtubule bundle, and displayed properties of bona fide microtubule-associated proteins such as tau. Red blood cell ferritin association with the marginal band was confirmed by temperature-induced disassembly-reassembly of microtubules. During erythrocyte differentiation, ferritin co-localized with coalescing microtubules during marginal band formation. In addition, ferritin was found in the nuclei of mature erythrocytes, but was not detectable in those of bone marrow erythrocyte precursors. These results suggest that ferritin has a function in marginal band formation and possibly in protection of the marginal band from damaging effects of reactive oxygen species by sequestering iron in the mature erythrocyte. Moreover, our data suggest that ferritin and syncolin, a previously identified erythrocyte microtubule-associated protein, are identical. Nuclear ferritin might contribute to transcriptional silencing or, alternatively, constitute a ferritin reservoir

  6. Electricity utility deregulation in Great Britain: economic and industrial consequences

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    In this paper we analyze in the first part how was made the deregulation of the public electric utilities in Great Britain and in the second the logic and the contradictions of this deregulation in an industrial point of view

  7. Lateral motion and bending of microtubules studied with a new single-filament tracking routine in living cells.

    Science.gov (United States)

    Pallavicini, Carla; Levi, Valeria; Wetzler, Diana E; Angiolini, Juan F; Benseñor, Lorena; Despósito, Marcelo A; Bruno, Luciana

    2014-06-17

    The cytoskeleton is involved in numerous cellular processes such as migration, division, and contraction and provides the tracks for transport driven by molecular motors. Therefore, it is very important to quantify the mechanical behavior of the cytoskeletal filaments to get a better insight into cell mechanics and organization. It has been demonstrated that relevant mechanical properties of microtubules can be extracted from the analysis of their motion and shape fluctuations. However, tracking individual filaments in living cells is extremely complex due, for example, to the high and heterogeneous background. We introduce a believed new tracking algorithm that allows recovering the coordinates of fluorescent microtubules with ∼9 nm precision in in vitro conditions. To illustrate potential applications of this algorithm, we studied the curvature distributions of fluorescent microtubules in living cells. By performing a Fourier analysis of the microtubule shapes, we found that the curvatures followed a thermal-like distribution as previously reported with an effective persistence length of ∼20 μm, a value significantly smaller than that measured in vitro. We also verified that the microtubule-associated protein XTP or the depolymerization of the actin network do not affect this value; however, the disruption of intermediate filaments decreased the persistence length. Also, we recovered trajectories of microtubule segments in actin or intermediate filament-depleted cells, and observed a significant increase of their motion with respect to untreated cells showing that these filaments contribute to the overall organization of the microtubule network. Moreover, the analysis of trajectories of microtubule segments in untreated cells showed that these filaments presented a slower but more directional motion in the cortex with respect to the perinuclear region, and suggests that the tracking routine would allow mapping the microtubule dynamical organization in cells

  8. Stabilization of microtubules by inorganic phosphate and its structural analogues, the fluoride complexes of aluminum and beryllium

    International Nuclear Information System (INIS)

    Carlier, M.F.; Didry, D.; Melki, R.; Chabre, M.; Pantaloni, D.

    1988-01-01

    In order to elucidate how the elementary reactions of GTP cleavage and subsequent inorganic phosphate (P/sub i/) release, which accompany microtubule assembly, regulate microtubule dynamics, the effect of P/sub i/ and of its structural analogues AlF 4 - and BeF 3 - on the stability of GDP-microtubules has been investigated. Inorganic phosphate binds to microtubules with a low affinity (K/sub D/ = 25 mM) and slows down the rate of GDP-subunit dissociation by about 2 orders of magnitude. AlF 4 - and BeF 3 - exhibit phosphate-like effects with 1000-fold higher affinity. Evidence has been obtained for direct binding of BeF 3 - to microtubules with a stoichiometry of 1 mol of BeF 3 - per mole of GDP-subunit and an equilibrium dissociation constant of 12-15 μM. AlF 4 - and P/sub i/ compete for this site. Phosphate analogues abolish oscillatory polymerization kinetics and slow down microtubule turnover at steady state. In view of these results, the authors propose that P/sub i/ and its structural analogues bind to the site of the γ-phosphate of GTP in the E site and reconstitute a GDP-P/sub i/-microtubule, from which tubulin subunits dissociate very slowly. They therefore understand that, following GTP cleavage on microtubules, P/sub i/ release in the medium is accompanied by a structural change resulting in a large destabilization of the polymer. A cap of slowly dissociating GDP-P/sub i/-subunits prevents depolymerization of the microtubule GDP-core at steady state. The similarity with the actin system is studied

  9. Industrial consumers and electricity sector deregulation

    International Nuclear Information System (INIS)

    Jukic, A.

    1999-01-01

    The paper presents the electricity sector deregulation from the point of view of major industrial consumers (MIC). Possibilities and limitations of MIC's impact on the introduction and development of an open power market in some European countries, the USA and Croatia are discussed. (author)

  10. IMPACT OF DEREGULATION ON FINANCIAL SECTOR ...

    African Journals Online (AJOL)

    and the efficiency in the allocation of the society's resources, which were not ... financial system so as to make the system operate on the basis of the market ..... cases, the null hypothesis that financial sector deregulation does not granger .... Financial Sector Development and Growth: Evidence from Malaysia, Brookings.

  11. Deregulation of natural gas in Georgia

    International Nuclear Information System (INIS)

    Wise, S.

    2002-01-01

    The Natural Gas Competition and Deregulation Act of 1997 in Georgia is discussed. New legislation passed the Natural Gas Consumer Relief Act in 2002 legislative session to provide additional protection and increase competition. This Act and its impacts are discussed in detail. Additional commission responsibilities are summarized. (R.P.)

  12. Regulatory concern about economic deregulation in Finland

    International Nuclear Information System (INIS)

    Virolainen, R.; Koutaniemi, P.

    2002-01-01

    The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

  13. Regulatory concern about economic deregulation in Finland

    International Nuclear Information System (INIS)

    Virolainen, R.; Koutaniemi, P.

    2001-01-01

    The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper, such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

  14. Wind power in a deregulated market

    International Nuclear Information System (INIS)

    Ravn, Hans F.

    2000-01-01

    The paper describes organisational and economic elements related to wind power in a deregulated market, it describes physical and technical characteristics of wind power and it describes how wind power is handled in daily operation as well as on the market. (author)

  15. Energy and the deregulated marketplace 1998 survey

    International Nuclear Information System (INIS)

    Fowler, R.B.

    1999-01-01

    In this comprehensive survey of the energy and deregulated marketplace, 911 respondents indicate how deregulation will impact their business. Well organized for easy reference this published survey report provides answers on how companies will procure electricity and natural gas, and what criteria will be used in their decision process. The results presented also illustrate effect of real time pricing on the procurement of energy equipment. Readers will be able to see whether companies are delaying the purchase of energy efficiency equipment as a result of deregulation, as well as what current trends are developing in the use of energy services and performance contracting. The performance and overall cost effectiveness of various types of energy efficient equipment is also rated by respondents, and the results of existing installations is reported. Responses are broken down and can be assessed by respondent categories, including utility, energy supplier, energy user, power marketer, ESCO, equipment supplier, and consultant. This survey report offers a valuable tool for all companies whose business and marketing strategies are impacted by deregulation

  16. SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

    Science.gov (United States)

    Lysko, Daniel E.; Putt, Mary

    2014-01-01

    Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process. PMID:24695713

  17. Stabilization, not polymerization, of microtubules inhibits the nuclear translocation of STATs in adipocytes

    International Nuclear Information System (INIS)

    Gleason, Evanna L.; Hogan, Jessica C.; Stephens, Jacqueline M.

    2004-01-01

    Signal transducers and activators of transcriptions (STATs) are a family of latent transcription factors which are activated by a variety of growth factors and cytokines in many cell types. However, the mechanism by which these transcription factors translocate to the nucleus is poorly understood. The goal of this study was to determine the requirement of microfilaments and microtubules for cytokine induced STAT activation in cultured adipocytes. We used seven different actin-specific and microtubule-specific agents that are well-established effectors of these cytoskeletal networks. Our results clearly demonstrate that inhibition of microfilaments or the prevention of microtubule polymerization has no effect on the ability of STATs to be tyrosine phosphorylated or to translocate to the nucleus. However, we observed that paclitaxel, a microtubule stabilizer, resulted in a significant decrease in the nuclear translocation of STATs without affecting the cytosolic tyrosine phosphorylation of these transcription factors. In summary, our results demonstrate that the dynamic instability, but not the polymerization, of microtubules contributes to nuclear translocation of STAT proteins in adipocytes

  18. SDF1 reduces interneuron leading process branching through dual regulation of actin and microtubules.

    Science.gov (United States)

    Lysko, Daniel E; Putt, Mary; Golden, Jeffrey A

    2014-04-02

    Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process.

  19. Microtubules move the nucleus to quiescence.

    Science.gov (United States)

    Laporte, Damien; Sagot, Isabelle

    2014-01-01

    The nucleus is a cellular compartment that hosts several macro-molecular machines displaying a highly complex spatial organization. This tight architectural orchestration determines not only DNA replication and repair but also regulates gene expression. In budding yeast microtubules play a key role in structuring the nucleus since they condition the Rabl arrangement in G1 and chromosome partitioning during mitosis through their attachment to centromeres via the kinetochore proteins. Recently, we have shown that upon quiescence entry, intranuclear microtubules emanating from the spindle pole body elongate to form a highly stable bundle that spans the entire nucleus. Here, we examine some molecular mechanisms that may underlie the formation of this structure. As the intranuclear microtubule bundle causes a profound re-organization of the yeast nucleus and is required for cell survival during quiescence, we discuss the possibility that the assembly of such a structure participates in quiescence establishment.

  20. Learning without experience: Understanding the strategic implications of deregulation and competition in the electricity industry

    Energy Technology Data Exchange (ETDEWEB)

    Lomi, A. [School of Economics, University of Bologna, Bologna (Italy); Larsen, E.R. [Dept. of Managements Systems and Information, City University Business School, London (United Kingdom)

    1998-11-01

    As deregulation of the electricity industry continues to gain momentum around the world, electricity companies face unprecedented challenges. Competitive complexity and intensity will increase substantially as deregulated companies find themselves competing in new industries, with new rules, against unfamiliar competitors - and without any history to learn from. We describe the different kinds of strategic issues that newly deregulated utility companies are facing, and the risks that strategic issues implicate. We identify a number of problems induced by experiential learning under conditions of competence-destroying change, and we illustrate ways in which companies can activate history-independent learning processes. We suggest that Micro worlds - a new generation of computer-based learning environments made possible by conceptual and technological progress in the fields of system dynamics and systems thinking - are particularly appropriate tools to accelerate and enhance organizational and managerial learning under conditions of increased competitive complexity. (au)

  1. Design of reactive power procurement in deregulated electricity market

    African Journals Online (AJOL)

    Reactive power management is different in the deregulated electricity market of various countries. In this paper, a novel reactive power procurement model is proposed, which ensure secure and reliable operation of deregulated electricity market. Various issues of reactive power management in the deregulated electricity ...

  2. Deregulation and competition in the electric utility marketplace

    International Nuclear Information System (INIS)

    Allen, J.E.

    1995-01-01

    This paper addresses the impact of deregulation and competition in the electric utility marketplace as an extension of the deregulation of the airlines, and natural gas, telephone and trucking industries. The topics of the paper include the events and circumstances leading to deregulation, those involved in the competition, and a scenario for how the industry will develop over the next 20 years

  3. Potential mechanisms of resistance to microtubule inhibitors.

    Science.gov (United States)

    Kavallaris, Maria; Annereau, Jean-Philippe; Barret, Jean-Marc

    2008-06-01

    Antimitotic drugs targeting the microtubules, such as the taxanes and vinca alkaloids, are widely used in the treatment of neoplastic diseases. Development of drug resistance over time, however, limits the efficacy of these agents and poses a clinical challenge to long-term improvement of patient outcomes. Understanding the mechanism(s) of drug resistance becomes paramount to allowing for alternative, if not improved, therapeutic options that might circumvent this challenge. Vinflunine, a novel microtubule inhibitor, has shown superior preclinical antitumor activity, and displays a different pattern of resistance, compared with other agents in the vinca alkaloid class.

  4. Game-theoretic equilibrium analysis applications to deregulated electricity markets

    Science.gov (United States)

    Joung, Manho

    This dissertation examines game-theoretic equilibrium analysis applications to deregulated electricity markets. In particular, three specific applications are discussed: analyzing the competitive effects of ownership of financial transmission rights, developing a dynamic game model considering the ramp rate constraints of generators, and analyzing strategic behavior in electricity capacity markets. In the financial transmission right application, an investigation is made of how generators' ownership of financial transmission rights may influence the effects of the transmission lines on competition. In the second application, the ramp rate constraints of generators are explicitly modeled using a dynamic game framework, and the equilibrium is characterized as the Markov perfect equilibrium. Finally, the strategic behavior of market participants in electricity capacity markets is analyzed and it is shown that the market participants may exaggerate their available capacity in a Nash equilibrium. It is also shown that the more conservative the independent system operator's capacity procurement, the higher the risk of exaggerated capacity offers.

  5. Deregulation of Electricity Supply Industry in Oman

    Directory of Open Access Journals (Sweden)

    Hamed S. Al-Maghderi

    2002-06-01

    Full Text Available This paper examines the opportunities available and the conditions needed for the deregulation of the Electricity Supply Industry (ESI, with particular reference to the Sultanate of Oman. The paper highlights the general issues of regulation required to encourage competition in the ESI.  After that, the discussion focuses on regulation methods in the privatized ESI by describing the regulators control through price caps setting for regulatees, the conduct regulation process, the rate of return regulation setting, and the spot market (the pool contract. Finally, the prospects of restructuring and privatizing the ESI in the Sultanate of Oman are examined by reviewing the current structure of the industry and government objectives in deregulation of the electricity sector as well as the regulation framework.

  6. Utilities' ''obligation to serve'' under deregulation

    International Nuclear Information System (INIS)

    Alexander, C.B.

    1997-01-01

    The utility no longer has protected status, and the traditional franchise concept is under attack. Exclusive rights once conveyed to the utilities are being denied and not just in the area of gas sales. Exclusive rights once conveyed to utilities will be denied in more areas. State by state, the utilities' franchise is being examined to see which, if any, of its provisions are necessary in a deregulated environment. Can the free market provide everything that's been provided for many years under monopolistic arrangements? Some of the most critical and difficult of these provisions concern the obligation to serve, which utilities, in most states, have assumed as part of their franchise agreement. Regulators, courts, utilities, marketers and others are busy sorting through these issues, but resolution could take years. The paper discusses deregulation, universal service fee, representation without taxation, suppliers and marketer restrictions

  7. Gas directive. Which deregulation for France

    International Nuclear Information System (INIS)

    1999-09-01

    This study deals with the following aspects of natural gas market: deregulation of the French market; status and perspectives of the gas market: overview of the gas supplies in Europe at the 2010/2015 vista; situation of regulations: status of the gas directive at the European level and impact on member states market, transposition of the gas directive in France: present day legislation, main stakes and situation of the dialogue with the actors; consequences and actors' strategy: testimony of suppliers, past and future situation, development of new activities in the gas/power industry, possible contractual evolutions, position of the supplier; testimony of clients: new suppliers, new contracts, new risks; legal stakes for the clients: impact of deregulation on contracts, future contractual organization of the market, evolution of 'take or pay' contracts, impairment of contracts obligations, negotiation of supply contracts. (J.S.)

  8. Network industries deregulation and energy industries reorganization

    International Nuclear Information System (INIS)

    Delaporte, P.; Chevalier, J.M.; Bourdaire, J.M.

    1999-01-01

    The electric power distribution systems deregulation is going to change the economical and institutional scenery. The empowerment term can be anything but a happy change for the customer by giving him the free choice. But this evolution calls the public power in question again. Meanwhile the government has to remain vigilant and watch over the safety in terms of cartel and environment risk. (A.L.B.)

  9. Energy subsidies in California's electricity market deregulation

    International Nuclear Information System (INIS)

    Ritschel, Alexander; Smestad, G.P.

    2003-01-01

    Deregulation and re-regulation of California's electricity market not only failed in terms of anticipated cost reductions, improved customer service and higher competition, it also led to the introduction of various additional energy subsidies. This paper analyzes California's electricity market deregulation process from a subsidy viewpoint. Under deregulation in California, investor-owned utilities were not allowed to pass their energy procurement costs fully on to their customers, and therefore subsequently, and inevitably, ran into severe financial problems. Such retail price regulation is an energy subsidy that is both economically and environmentally unfavorable, because it veils true price signals to electricity consumers and, in this way, discourages energy conservation. Other policies implemented in California that represent perverse energy subsidies are the purchase of power by the state of California, the suspension of retail competition, and the potential misuse of money from the recovery of stranded costs. Many interventions implemented by the state to smooth out the impacts of the energy crisis insulated electricity consumers from market realities, supported the existing structure of California's electricity market, which is predominantly based on fossil fuels, and suppressed market incentives to improve energy conservation

  10. Deregulated power prices: comparison of volatility

    International Nuclear Information System (INIS)

    Li Ying; Flynn, P.C.

    2004-01-01

    We examine electrical power price variability for 14 deregulated markets. Power price volatility is measured by price velocity, the daily average of the absolute value of price change per hour. Deregulated markets show a wide variability in price velocity. Some price velocity is expected and arises from the daily diurnal price pattern, which differs significantly between markets. Even when the expected daily variability in price is removed, the residual unexpected variability differs between markets. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent and have low values of unexpected price velocity. These markets create a climate conducive to consumers facing the market through real time pricing and shaping consumption behaviors in response to price changes. Other markets, for example, South Australia and Alberta, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to avoid demand side management and escape risk through hedging mechanisms

  11. Gas and electricity 2000: energy deregulation

    International Nuclear Information System (INIS)

    Hulot, J.C.; Charbit, N.; Tuot, Th.

    2000-11-01

    This document brings together 17 testimonies of experts about the deregulation of the gas and electricity markets. Content: 1 - the new rules controlling the market: schedule and regulatory evolutions, the new legal framework, the new regulation, the missions and competences of the Commission of Electricity Regulation; 2 - the new commercial practices: the question of electricity transport and of the network independence, the development of trading, the stock exchanges and the forecasting of Paris market, the correlations with the environment (eco-taxes and climate change); 3 - the proposals of new actors: the contribution of a deregulated market like Spain, the comparison with a fully open market like Germany, an internal out-sourcing example to create an energy entity as a whole, the role of a bank in the risk management and the derived markets, the contribution of new technologies from service suppliers; 4 - the consumers attitude with respect to new offers: the historical gas and electricity utilities at the service of French and European clients, the new opportunities offered by the deregulation, the contribution of an independent supplier to consumers, the expectations of big companies and eligible consumers. (J.S.)

  12. TCS1, a Microtubule-Binding Protein, Interacts with KCBP/ZWICHEL to Regulate Trichome Cell Shape in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Liangliang Chen

    2016-10-01

    Full Text Available How cell shape is controlled is a fundamental question in developmental biology, but the genetic and molecular mechanisms that determine cell shape are largely unknown. Arabidopsis trichomes have been used as a good model system to investigate cell shape at the single-cell level. Here we describe the trichome cell shape 1 (tcs1 mutants with the reduced trichome branch number in Arabidopsis. TCS1 encodes a coiled-coil domain-containing protein. Pharmacological analyses and observations of microtubule dynamics show that TCS1 influences the stability of microtubules. Biochemical analyses and live-cell imaging indicate that TCS1 binds to microtubules and promotes the assembly of microtubules. Further results reveal that TCS1 physically associates with KCBP/ZWICHEL, a microtubule motor involved in the regulation of trichome branch number. Genetic analyses indicate that kcbp/zwi is epistatic to tcs1 with respect to trichome branch number. Thus, our findings define a novel genetic and molecular mechanism by which TCS1 interacts with KCBP to regulate trichome cell shape by influencing the stability of microtubules.

  13. Explaining the Microtubule Energy Balance: Contributions Due to Dipole Moments, Charges, van der Waals and Solvation Energy

    Directory of Open Access Journals (Sweden)

    Ahmed Taha Ayoub

    2017-09-01

    Full Text Available Microtubules are the main components of mitotic spindles, and are the pillars of the cellular cytoskeleton. They perform most of their cellular functions by virtue of their unique dynamic instability processes which alternate between polymerization and depolymerization phases. This in turn is driven by a precise balance between attraction and repulsion forces between the constituents of microtubules (MTs—tubulin dimers. Therefore, it is critically important to know what contributions result in a balance of the interaction energy among tubulin dimers that make up microtubules and what interactions may tip this balance toward or away from a stable polymerized state of tubulin. In this paper, we calculate the dipole–dipole interaction energy between tubulin dimers in a microtubule as part of the various contributions to the energy balance. We also compare the remaining contributions to the interaction energies between tubulin dimers and establish a balance between stabilizing and destabilizing components, including the van der Waals, electrostatic, and solvent-accessible surface area energies. The energy balance shows that the GTP-capped tip of the seam at the plus end of microtubules is stabilized only by − 9 kcal/mol, which can be completely reversed by the hydrolysis of a single GTP molecule, which releases + 14 kcal/mol and destabilizes the seam by an excess of + 5 kcal/mol. This triggers the breakdown of microtubules and initiates a disassembly phase which is aptly called a catastrophe.

  14. Dinitroaniline herbicide resistance and the microtubule cytoskeleton.

    Science.gov (United States)

    Anthony; Hussey

    1999-03-01

    Dinitroaniline herbicides have been used for pre-emergence weed control for the past 25 years in cotton, soybean, wheat and oilseed crops. Considering their long persistence and extensive use, resistance to dinitroanilines is fairly rare. However, the most widespread dinitroaniline-resistant weeds, the highly resistant (R) and the intermediate (I) biotypes of the invasive goosegrass Eleusine indica, are now infesting more than 1000 cotton fields in the southern states of the USA. The molecular basis of this resistance has been identified, and found to be a point mutation in a major microtubule cytoskeletal protein, alpha-tubulin. These studies have served both to explain the establishment of resistance and to reveal fundamental properties of tubulin gene expression and microtubule structure.

  15. Dynamics and regulation at the tip : a high resolution view on microtubele assembly

    NARCIS (Netherlands)

    Munteanu, Laura

    2008-01-01

    Microtubules are highly dynamic protein polymers that and are essential for intracellular organization and fundamental processes like transport and cell division. In cells, a wide family of microtubule-associated proteins (MAPs) tightly regulates microtubule dynamics. The work presented in this

  16. Deregulated gas in 1985 seen costly

    Energy Technology Data Exchange (ETDEWEB)

    Schaffer, P.

    1980-05-05

    Deregulation of natural gas wellhead prices will mean higher prices for nonboiler industrial users, according to an Energy and Environmental Analysis Inc. (EEA) study. The price increases of high-sulfur residual fuel oil will exceed inflation rates, but low-sulfur residual oil and distillate oil will have smaller increases because of upgraded refineries. Te economc imact analysis is broken down by region and includes estimates of gas, high-sulfur coal, and low-sulfur coal prices thrugh 1995. Free copies of the report are available from the Federal Energy Regulatory Commission's Office of Public Information. (DCK)

  17. Immunological Deregulation in Classic Hodgkin Lymphoma

    Science.gov (United States)

    Romano, Alessandra; Vetro, Calogero; Caocci, Giovanni; Greco, Marianna; Parrinello, Nunziatina Laura; Di Raimondo, Francesco; La Nasa, Giorgio

    2014-01-01

    Classic Hodgkin Lymphoma (cHL) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in regulatory T cells signaling, expansion of myeloid derived suppressor cells, HLA-G signaling and natural killer cells dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in cHL with translational implications. PMID:24959336

  18. Controversies about gas industry deregulation in Europe

    International Nuclear Information System (INIS)

    Percebois, J.

    1992-01-01

    The E.E.C. Commission wishes to introduce more competition into the European gas industry; abolish import public monopolies, resort to competitive bidding for distribution concessions, and to the common carrier system in the transport field. This deregulation policy may induce adverse effects in the long run. This may compromise supply security, and delay the development of new gas fields. This may particularly induce subsidies among users and lead to a reinforcement of regulation if we want the Third Party Access system to respect equality conditions for all users. This paper analyzes arguments for and against this common carrier system. 15 refs., 2 figs

  19. Electric deregulation in Texas : the next steps

    International Nuclear Information System (INIS)

    Giuliani, R.

    2004-01-01

    This presentation provided a look at the deregulated market in Texas and provided some statistics and facts about the Electric Reliability Council of Texas (ERCOT) which monitors the reliability of 37,000 miles of power transmission lines and 77,000 MW of generation. The governance adopted by ERCOT was described along with market design and wholesale operation in terms of open access to transmission and distribution systems, reliability, timely conveyance of information needed to support customer choice, and accurate accountability for electricity production and delivery. Transmission has been one the greatest challenges facing ERCOT, but retail operations are progressing well despite initial start-up problems. tabs., figs

  20. Novel mitochondrial extensions provide evidence for a link between microtubule-directed movement and mitochondrial fission

    International Nuclear Information System (INIS)

    Bowes, Timothy; Gupta, Radhey S.

    2008-01-01

    Mitochondrial dynamics play an important role in a large number of cellular processes. Previously, we reported that treatment of mammalian cells with the cysteine-alkylators, N-ethylmaleimide and ethacrynic acid, induced rapid mitochondrial fusion forming a large reticulum approximately 30 min after treatment. Here, we further investigated this phenomenon using a number of techniques including live-cell confocal microscopy. In live cells, drug-induced fusion coincided with a cessation of fast mitochondrial movement which was dependent on microtubules. During this loss of movement, thin mitochondrial tubules extending from mitochondria were also observed, which we refer to as 'mitochondrial extensions'. The formation of these mitochondrial extensions, which were not observed in untreated cells, depended on microtubules and was abolished by pretreatment with nocodazole. In this study, we provide evidence that these extensions result from of a block in mitochondrial fission combined with continued application of motile force by microtubule-dependent motor complexes. Our observations strongly suggest the existence of a link between microtubule-based mitochondrial trafficking and mitochondrial fission

  1. Vault mobility depends in part on microtubules and vaults can be recruited to the nuclear envelope

    International Nuclear Information System (INIS)

    Zon, Arend van; Mossink, Marieke H.; Houtsmuller, Adriaan B.; Schoester, Martijn; Scheffer, George L.; Scheper, Rik J.; Sonneveld, Pieter; Wiemer, Erik A.C.

    2006-01-01

    Vaults are ribonucleoproteins that may function in intracellular transport processes. We investigated the intracellular distribution and dynamics of vaults in non-small cell lung cancer cells in which vaults are labeled with the green fluorescent protein. Immunofluorescence experiments showed that vaults are dispersed throughout the cytoplasm; a small fraction is found in close proximity to microtubules. Immunoprecipitation experiments corroborated these results showing co-precipitation of MVP and β-tubulin. Using quantitative fluorescence-recovery after photobleaching (FRAP), we demonstrated that vault mobility over longer distances in part depends on intact microtubules; vaults moving slower when microtubules are depolymerized by nocodazole. Biochemical fractionation indicated a small fraction of MVP associated with the nucleus, however, no GFP-tagged vaults could be observed inside the nucleus. We observed an accumulation of vaults at the nuclear envelope upon treatment of cells with the protein synthesis inhibitor cycloheximide. Analysis of nucleo-cytoplasmic transport using a fluorescent substrate containing a classical NLS and NES expressed in MVP +/+ and MVP -/- mouse embryonic fibroblasts indicated no differences in nuclear import/export kinetics, suggesting no role for vaults in these processes. We hypothesize that a subset of vaults moves directionally via microtubules, possibly towards the nucleus

  2. Transient phosphorylation of tumor associated microtubule associated protein (TMAP)/cytoskeleton associated protein 2 (CKAP2) at Thr-596 during early phases of mitosis

    OpenAIRE

    Hong, Kyung Uk; Choi, Yong-Bock; Lee, Jung-Hwa; Kim, Hyun-Jun; Kwon, Hye-Rim; Seong, Yeon-Sun; Kim, Heung Tae; Park, Joobae; Bae, Chang-Dae; Hong, Kyeong-Man

    2008-01-01

    Tumor associated microtubule associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2) is a mitotic spindle-associated protein whose expression is cell cycle-regulated and also frequently deregulated in cancer cells. Two monoclonal antibodies (mAbs) against TMAP/CKAP2 were produced: B-1-13 and D-12-3. Interestingly, the reactivity of mAb D-12-3 to TMAP/CKAP2 was markedly decreased specifically in mitotic cell lysate. The epitope mapping study showed that mAb D-12-3 re...

  3. Deregulation, privatization and the Ontario power failure

    International Nuclear Information System (INIS)

    2003-09-01

    The Canadian Union of Public Employees (CUPE) has examined the history of deregulation of the electricity industry in the United States and presents lessons that could be learned from the California electricity crisis, the collapse of Enron, and the massive blackout that occurred in August 2003 across Ontario and northeastern United States. Unlike the United States, Canada's electricity system is mostly publicly owned and operated. This report emphasized that the need for public investment in the electricity system is greater than ever, and offers suggestions on how to strengthen the Canadian electricity system. It examines the attempts made to deregulate and privatize the electricity system in Ontario, Alberta, New Brunswick and British Columbia and exposes the reality of price caps and the debt of public utilities. It demonstrates that privatization has failed to provide a safe, reliable, affordable and adequate supply of electricity. The report claims that profit-seeking power producers want to keep supply and demand in their favour to sell electricity at the highest possible price. In addition to emphasizing the need for public investment in the electricity system, this report emphasizes the need for Canadian electricity cooperation, with particular mention of the large energy supplies in Manitoba and Quebec. 37 refs

  4. Zap... Alberta is jolted by electric deregulation

    International Nuclear Information System (INIS)

    Howe, M.E.

    2001-01-01

    Of all Canadian provinces, Alberta has travelled the furthest along the electric deregulation road. On January 1, 2001, full retail competition came into effect. Wholesale electricity prices are set by the province through an auction process. The bids from purchasers are made through the Power Pool of Alberta against supply offers. Power prices increased from being amongst the lowest in the world to being amongst the highest in North America as a result of deregulation. Changes to the Electric Utilities Act were made recently by the Alberta government to try to mitigate the factors affecting power price increases. RBC Dominion Securities is of the opinion that the changes will not significantly impact the Alberta Pool Price. It is expected that the trend for power price increases to continue, despite some relief from relatively low-cost electricity being felt by other Canadian provinces as a result of the energy crisis in North America. Based on the Electric Competition Unfolds in Alberta report dated June 2, 2001 prepared by RBC Dominion Securities, this document examines the factors at play in electric price increases, assess the sustainability of current power prices in Alberta, and identify Canadian companies believed to be best positioned in the pipeline and gas and electric sectors to benefit from the high power prices in Alberta. Those companies were ATCO, Canadian Utilities, Westcoast Energy and TransCanada PipeLines, and TransAlta. 5 tabs., 5 figs

  5. Selling power : marketing energy under deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Drummond, J.; Hanna, F.

    2001-07-01

    This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs.

  6. Competing in a fully deregulated market

    International Nuclear Information System (INIS)

    Bengtsson, A.; Schoen, G.; Johansson, B.

    1999-01-01

    Vattenfall, Sweden's largest utility, has provided competitively priced nuclear electricity to a price-conscious market for several decades. As Sweden is an exporting country, the cost of products must be kept as low as possible to meet tough European competition. Since Sweden relies almost exclusively on electricity for energy, electric prices must be low to keep Swedish products competitive. Because of the available hydropower in Sweden and Norway, nuclear power plants have been forced to operate with high availability and low cost. From the first years after nuclear plants began operation, there has been a continuous development of organization, management, and work practices to sustain low-cost production. Now, the European electricity market is undergoing deregulation and open competition. This is taking place in a situation where the increase in demand is relatively weak and where the availability of generation capacity is good. Sweden is at the forefront of the competition. According to the well-known law of supply and demand, this entails the risk of squeezed prices, but the situation also offers many opportunities for those making the right decisions. The availability of electricity at competitive prices has great significance for the competitiveness of the industry in general and for the electricity-intensive industry in particular. If the customer then, in a deregulated market is free to choose the supplier, the focus definitely is on the customer

  7. Deregulation : unlocking value : the Australian experience

    International Nuclear Information System (INIS)

    Kwok, F.

    2002-01-01

    Macquarie is a global investment bank based in Australia whose international focus is on niche markets such as infrastructure and utilities. A corporate review of Macquarie is presented along with a review of the evolution of the utility industry from the stages of an integrated utility to fully unbundled entities. In the first stage, the utility is vertically integrated and owned by government, or it is highly regulated. The second stage of evolution involves the unbundling of the utility into separate generation, transmission and distribution companies, each preparing for competition. The third stage involves the introduction of competition to power generation and retail sectors. Transmission and distribution remains regulated in the third stage. The fourth stage involves down-sizing in response to competition and benchmarking. It is also a period of convergence between electricity and gas. The fifth and final stage is for deriving value. Deregulation results in major structural changes and utility managers have to decide how the utility can best deliver value to the shareholders in the new environment. The author discusses how these lessons can be applied to the case of electric power industry deregulation in Alberta

  8. Energy service unbundling: where deregulation is heading

    International Nuclear Information System (INIS)

    Croft, M.

    2002-01-01

    The workings of the natural gas market is provided by the speaker at the beginning of the presentation, and covers pre-regulation, early regulation and deregulation. The pre-regulation era provided no customer choice, and the early regulation period saw industrial customers with some degree of choice (mid-1980s). The advent of deregulation created core market customer choice (around 1996). At Coral Energy, there is choice of energy supplier, choice of price structure, and choice of transportation and distribution. A forecast of North American gas demand is provided, along with the natural gas supply and the North American gas supply basins. For the period January 1996 to May 2000, a comparison of annualized volatility is discussed. The author discusses the strategies for purchasing gas: 1) to know yourself and your risk tolerance, flexibility, and load profile; 2) switching gas supply provider. It is important to choose a three year term, combination pricing, and storage position. The risk management options are reviewed: limit exposure to price volatility, mitigate price/volume volatility, and enhance bottom line by capturing market opportunities. figs

  9. Selling power : marketing energy under deregulation

    International Nuclear Information System (INIS)

    Drummond, J.; Hanna, F.

    2001-01-01

    This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs

  10. Transmission management in the deregulated environment

    International Nuclear Information System (INIS)

    Christie, R.D.; Wollenberg, B.F.; Wangensteen, I.

    2000-01-01

    Three very different methods of accomplishing the same task--managing the operation of the transmission system in the deregulated power system operating environment--have been implemented as deregulated market structures have been created around the world. They are first, the optimal power flow (OPF) model found in various implementations in the United Kingdom, parts of the United States, and in Australia and New Zealand. Second, the point tariff, price area congestion control model used in the Nordpool market area in Norway and Sweden. Third, the US transaction-based model. All are pragmatic solutions implemented in advance of complete theoretical understanding. Each has strengths and flaws, and there are some surprising inter-relationships. Each maintains power system security but differs in its impact on the economics of the energy market. No clearly superior method has so far emerged. In the future, methods of combining decentralized market solutions with operational use of optimal power flow may provide better solutions to existing and emerging problems

  11. Microtubules are organized independently of the centrosome in Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Nguyen Michelle M

    2011-12-01

    Full Text Available Abstract Background The best-studied arrangement of microtubules is that organized by the centrosome, a cloud of microtubule nucleating and anchoring proteins is clustered around centrioles. However, noncentrosomal microtubule arrays are common in many differentiated cells, including neurons. Although microtubules are not anchored at neuronal centrosomes, it remains unclear whether the centrosome plays a role in organizing neuronal microtubules. We use Drosophila as a model system to determine whether centrosomal microtubule nucleation is important in mature neurons. Results In developing and mature neurons, centrioles were not surrounded by the core nucleation protein γ-tubulin. This suggests that the centrioles do not organize functional centrosomes in Drosophila neurons in vivo. Consistent with this idea, centriole position was not correlated with a specific region of the cell body in neurons, and growing microtubules did not cluster around the centriole, even after axon severing when the number of growing plus ends is dramatically increased. To determine whether the centrosome was required for microtubule organization in mature neurons, we used two approaches. First, we used DSas-4 centriole duplication mutants. In these mutants, centrioles were present in many larval sensory neurons, but they were not fully functional. Despite reduced centriole function, microtubule orientation was normal in axons and dendrites. Second, we used laser ablation to eliminate the centriole, and again found that microtubule polarity in axons and dendrites was normal, even 3 days after treatment. Conclusion We conclude that the centrosome is not a major site of microtubule nucleation in Drosophila neurons, and is not required for maintenance of neuronal microtubule organization in these cells.

  12. Detection of deregulated modules using deregulatory linked path.

    Directory of Open Access Journals (Sweden)

    Yuxuan Hu

    Full Text Available The identification of deregulated modules (such as induced by oncogenes is a crucial step for exploring the pathogenic process of complex diseases. Most of the existing methods focus on deregulation of genes rather than the links of the path among them. In this study, we emphasize on the detection of deregulated links, and develop a novel and effective regulatory path-based approach in finding deregulated modules. Observing that a regulatory pathway between two genes might involve in multiple rather than a single path, we identify condition-specific core regulatory path (CCRP to detect the significant deregulation of regulatory links. Using time-series gene expression, we define the regulatory strength within each gene pair based on statistical dependence analysis. The CCRPs in regulatory networks can then be identified using the shortest path algorithm. Finally, we derive the deregulated modules by integrating the differential edges (as deregulated links of the CCRPs between the case and the control group. To demonstrate the effectiveness of our approach, we apply the method to expression data associated with different states of Human Epidermal Growth Factor Receptor 2 (HER2. The experimental results show that the genes as well as the links in the deregulated modules are significantly enriched in multiple KEGG pathways and GO biological processes, most of which can be validated to suffer from impact of this oncogene based on previous studies. Additionally, we find the regulatory mechanism associated with the crucial gene SNAI1 significantly deregulated resulting from the activation of HER2. Hence, our method provides not only a strategy for detecting the deregulated links in regulatory networks, but also a way to identify concerning deregulated modules, thus contributing to the target selection of edgetic drugs.

  13. Producing Conditional Mutants for Studying Plant Microtubule Function

    Energy Technology Data Exchange (ETDEWEB)

    Richard Cyr

    2009-09-29

    The cytoskeleton, and in particular its microtubule component, participates in several processes that directly affect growth and development in higher plants. Normal cytoskeletal function requires the precise and orderly arrangement of microtubules into several cell cycle and developmentally specific arrays. One of these, the cortical array, is notable for its role in directing the deposition of cellulose (the most prominent polymer in the biosphere). An understanding of how these arrays form, and the molecular interactions that contribute to their function, is incomplete. To gain a better understanding of how microtubules work, we have been working to characterize mutants in critical cytoskeletal genes. This characterization is being carried out at the subcellular level using vital microtubule gene constructs. In the last year of funding colleagues have discovered that gamma-tubulin complexes form along the lengths of cortical microtubules where they act to spawn new microtubules at a characteristic 40 deg angle. This finding complements nicely the finding from our lab (which was funded by the DOE) showing that microtubule encounters are angle dependent; high angles encounters results in catastrophic collisions while low angle encounters result in favorable zippering. The finding of a 40 deg spawn of new microtubules from extant microtubule, together with aforementioned rules of encounters, insures favorable co-alignment in the array. I was invited to write a New and Views essay on this topic and a PDF is attached (News and Views policy does not permit funding acknowledgments and so I was not allowed to acknowledge support from the DOE).

  14. How biological microtubules may avoid decoherence

    International Nuclear Information System (INIS)

    Hameroff, S.

    2005-01-01

    Full text: Entangled superpositions persisting for hundreds of milliseconds in protein assemblies such as microtubules (MTs) are proposed in biological functions, e.g. quantum computation relevant to consciousness in the Penrose-Hameroff 'Orch OR' model. Cylindrical polymers of the protein tubulin, MTs organize cell activities. The obvious question is how biological quantum states could avoid decoherence, e.g. in the brain at 37.6 degrees centigrade. Screening/sheelding: tubulin protein states/functions are governed by van der Waals London forces, quantum interactions among clouds of delocalizable electrons in nonpolar 'hydrophobic' intra-protein pockets screened from external van der Waals thermal interactions. Such pockets include amino acid resonance structures benzene and indole rings. (Anesthetic gases erase consciousness solely by interfering with London forces in hydrophobic pockets in various brain proteins). Hence tubulin states may act as superpositioned qubits also shielded at the MT level by counter-ion Debye plasma layers (due to charged C-termini tails on tubulin) and by water-ordering actin gels which embed MTs in a quasi-solid. Biological systems may also exploit thermodynamic gradients to give extremely low effective temperatures. Decoherence free subspaces: paradoxically, a system coupled strongly to its environment through certain degrees of freedom can effectively 'freeze' other degrees of freedom (quantum Zeno effect), enabling coherent superpositions and entanglement to persist. Metabolic energy supplied to MT collective dynamics (e.g. Froehlich coherence) can cause Bose-Einstein condenzation and counter decoherence as lasers avoid decoherence at room temperature. Topological quantum error correction: MT lattice structure reveals various helical winding paths through adjacent tubulins which follow the Fibonacci series. Propagation/interactions of quasi-particles along these paths may process information. As proposed by Kitaev (1997), various

  15. Duplication in the microtubule-actin cross-linking factor 1 gene causes a novel neuromuscular condition

    DEFF Research Database (Denmark)

    Jørgensen, Louise H; Mosbech, Mai-Britt; Færgeman, Nils J

    2014-01-01

    Spectrins and plakins are important communicators linking cytoskeletal components to each other and to cellular junctions. Microtubule-actin cross-linking factor 1 (MACF1) belongs to the spectraplakin family and is involved in control of microtubule dynamics. Complete knock out of MACF1 in mice...... muscles and diminished motor skills, with heterogeneous presentation among the affected family members. To corroborate these findings we used RNA interference to knock down the VAB-10 locus containing the MACF1 homologue in C. elegans, and we could show that this also causes movement disturbances...

  16. Deregulation in environmental policy. Aufsaetze zur Wirtschaftspolitik

    Energy Technology Data Exchange (ETDEWEB)

    Orth, J

    1983-01-01

    In the USA the attempt is being made for the first time to leave the solution of the apparent conflict between economy and ecology to a considerable extent to the powers of the market. The framework conditions and rules for that market are characterized by the new approaches of 'deregulation': 'They create a market in which business can make a profit by producing clean air and water.' The aim of the volume is to present that new strategy, with regard to the sector of air pollution, in its individual components, explain their mode of function and briefly indicate associated problems. However, before dealing with the new approaches based on free enterprise, the publication provides some basic information current legislation in the USA regarding air pollution.

  17. Regulatory trends : deregulation, where in the world is it working?

    International Nuclear Information System (INIS)

    Sofield, J.

    2001-01-01

    The issue of electricity deregulation was the focus of this Power-Point presentation, which discussed what deregulation entails, what it is meant to achieve and whether there is only one right answer. Different approaches and performance results were presented with reference to international experiences in the United Kingdom, Australia, New Zealand, and California. The main objective of deregulation is introduce competition to give customers a choice between suppliers and products, to allow market forces to set prices with the hope that they will be lower, and to encourage industry efficiency, reduce costs, improve productivity, and ensure that the right investments are made. The underlying agenda is to raise billions of dollars to reduce government debt and to transfer the risks and investment requirements to the investors and away from the government/taxpayers and ratepayers. Deregulation entails restructuring, privatization and unbundling of monopolies. It also entails a set of market rules and new systems processes to enable retail competition. The author emphasized that there are different characteristics to deregulation in each jurisdiction and that the state of the pre-deregulation industry plays a significant role in the eventual success of deregulation. The lessons learned from international experience is that open, non-discriminatory access is essential for both transmission and distribution and that political will for restructuring is essential. It was also determined that partial deregulation will not work, since wholesale and retail markets are connected. It was concluded that deregulation can work to different degrees under different designs. Progress so far has been slow and customers have yet to see the full benefits of deregulation. tabs

  18. Optomechanical proposal for monitoring microtubule mechanical vibrations

    Czech Academy of Sciences Publication Activity Database

    Barzanjeh, Sh.; Salari, V.; Tuszynski, J. A.; Cifra, Michal; Simon, C.

    2017-01-01

    Roč. 96, č. 1 (2017), č. článku 012404. ISSN 2470-0045 R&D Projects: GA ČR(CZ) GA15-17102S Grant - others:AV ČR(CZ) SAV-15-22 Program:Bilaterální spolupráce Institutional support: RVO:67985882 Keywords : Vibrational modes * Microtubule * Resonance frequencies Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 2.366, year: 2016

  19. Emerging microtubule targets in glioma therapy

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Reginato, M.J.; Baas, P.W.; D'Agostino, L.; Legido, A.; Tuszynski, J. A.; Dráberová, Eduarda; Dráber, Pavel

    2015-01-01

    Roč. 22, č. 1 (2015), s. 49-72 ISSN 1071-9091 R&D Projects: GA MŠk LH12050; GA MZd NT14467 Grant - others:GA AV ČR M200521203PIPP; NIH(US) R01 NS028785; Philadelphia Health Education Corporation (PHEC)–St. Christopher’s Hospital for Children Reunified Endowment (C.D.K.)(US) 323256 Institutional support: RVO:68378050 Keywords : glioma tumorigenesis * glioblastoma * tubulin * microtubules Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.303, year: 2015

  20. Deregulation experiences in Alberta and Ontario

    International Nuclear Information System (INIS)

    Axford, D.

    2003-01-01

    A brief introduction of Nexen Chemicals, one of the largest producers of sodium chlorate in the world, was offered, and a map displaying its locations throughout the world was displayed. Nexen is one of Canada's largest independent oil and gas producers, while Nexen Marketing is involved in the marketing of natural gas in North America. In January 2001, the deregulated market opened in Alberta. High natural gas prices, generation shortages, high prices in California and an upcoming provincial election all combined to complicate the situation. A high degree of volatility characterized the market. A chart displaying weekly average Alberta power and gas prices from Jan 2002 to 13 Oct 2002 was shown. In Ontario, the market opened in May 2002, and the demand growth rate was in the 1 to 2 per cent range. The author indicated that approximately 20 per cent of homeowners in Ontario have signed deals with retailers, contrary to Alberta where very few have done so. A similar chart displaying weekly average Ontario power prices was presented. The issues in Ontario are: consistency in policy, increase market transparency, transmission / distribution price flexibility, overall transmission / distribution to industrial consumers high, and increasing costs of the system operator. In Alberta, the issues are: government intent, congestion management issues, and billing settlement errors that continue. The opportunities offered by a deregulated market include process responsiveness which is rewarded, the ability to look in forward prices when prices fit margin requirement, and gives companies the opportunity to participate in the development of the market. Various charts were also displayed to further illustrate the market in both Alberta and Ontario. figs

  1. In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase.

    Directory of Open Access Journals (Sweden)

    Yoke-Peng Lee

    Full Text Available Under the fluctuating circumstances provided by the innate dynamics of microtubules and opposing tensions resulted from microtubule-associated motors, it is vital to ensure stable kinetochore-microtubule attachments for accurate segregation. However, a comprehensive understanding of how this regulation is mechanistically achieved remains elusive. Using our newly designed live cell FRET time-lapse imaging, we found that post-metaphase RanGTP is crucial in the maintenance of stable kinetochore-microtubule attachments by regulating Aurora B kinase via the NES-bearing Mst1. More importantly, our study demonstrates that by ensuring stable alignment of metaphase chromosomes prior to segregation, RanGTP is indispensible in governing the genomic integrity and the fidelity of cell cycle progression. Our findings suggest an additional role of RanGTP beyond its known function in mitotic spindle assembly during the prometaphase-metaphase transition.

  2. Quantitative analysis of microtubule orientation in interdigitated leaf pavement cells.

    Science.gov (United States)

    Akita, Kae; Higaki, Takumi; Kutsuna, Natsumaro; Hasezawa, Seiichiro

    2015-01-01

    Leaf pavement cells are shaped like a jigsaw puzzle in most dicotyledon species. Molecular genetic studies have identified several genes required for pavement cells morphogenesis and proposed that microtubules play crucial roles in the interdigitation of pavement cells. In this study, we performed quantitative analysis of cortical microtubule orientation in leaf pavement cells in Arabidopsis thaliana. We captured confocal images of cortical microtubules in cotyledon leaf epidermis expressing GFP-tubulinβ and quantitatively evaluated the microtubule orientations relative to the pavement cell growth axis using original image processing techniques. Our results showed that microtubules kept parallel orientations to the growth axis during pavement cell growth. In addition, we showed that immersion treatment of seed cotyledons in solutions containing tubulin polymerization and depolymerization inhibitors decreased pavement cell complexity. Treatment with oryzalin and colchicine inhibited the symmetric division of guard mother cells.

  3. Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

    Science.gov (United States)

    Fuentes, Federico

    2009-01-01

    PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity. PMID:19158394

  4. Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2

    Science.gov (United States)

    Petry, Sabine; Groen, Aaron C.; Ishihara, Keisuke; Mitchison, Timothy J.; Vale, Ronald D.

    2013-01-01

    Summary The microtubules that comprise mitotic spindles in animal cells are nucleated at centrosomes and by spindle assembly factors that are activated in the vicinity of chromatin. Indirect evidence also has suggested that microtubules might be nucleated from pre-existing microtubules throughout the spindle, but this process has not been observed directly. Here, we demonstrate microtubule nucleation from the sides of existing microtubules in meiotic Xenopus egg extracts. Daughter microtubules grow at a low branch angle and with the same polarity as mother filaments. Branching microtubule nucleation requires gamma-tubulin and augmin and is stimulated by GTP-bound Ran and its effector TPX2, factors previously implicated in chromatin-stimulated nucleation. Because of the rapid amplification of microtubule numbers and the preservation of microtubule polarity, microtubule-dependent microtubule nucleation is well suited for spindle assembly and maintenance. PMID:23415226

  5. KIF7 Controls the Proliferation of Cells of the Respiratory Airway through Distinct Microtubule Dependent Mechanisms.

    Directory of Open Access Journals (Sweden)

    Garry L Coles

    2015-10-01

    Full Text Available The cell cycle must be tightly coordinated for proper control of embryonic development and for the long-term maintenance of organs such as the lung. There is emerging evidence that Kinesin family member 7 (Kif7 promotes Hedgehog (Hh signaling during embryonic development, and its misregulation contributes to diseases such as ciliopathies and cancer. Kif7 encodes a microtubule interacting protein that controls Hh signaling through regulation of microtubule dynamics within the primary cilium. However, whether Kif7 has a function in nonciliated cells remains largely unknown. The role Kif7 plays in basic cell biological processes like cell proliferation or cell cycle progression also remains to be elucidated. Here, we show that Kif7 is required for coordination of the cell cycle, and inactivation of this gene leads to increased cell proliferation in vivo and in vitro. Immunostaining and transmission electron microscopy experiments show that Kif7dda/dda mutant lungs are hyperproliferative and exhibit reduced alveolar epithelial cell differentiation. KIF7 depleted C3H10T1/2 fibroblasts and Kif7dda/dda mutant mouse embryonic fibroblasts have increased growth rates at high cellular densities, suggesting that Kif7 may function as a general regulator of cellular proliferation. We ascertained that in G1, Kif7 and microtubule dynamics regulate the expression and activity of several components of the cell cycle machinery known to control entry into S phase. Our data suggest that Kif7 may function to regulate the maintenance of the respiratory airway architecture by controlling cellular density, cell proliferation, and cycle exit through its role as a microtubule associated protein.

  6. Electric utility deregulation - A nuclear opportunity

    International Nuclear Information System (INIS)

    DeMella, J.R.

    2002-01-01

    The implications of electric deregulation are and will continue to be pervasive and significant. Not only will the fundamental monopoly regulatory concepts of managing electric utilities change but deregulation will have a profound and dramatic impact on the way electric generating plants are managed and operated. In the past, under the various approaches to financial regulation, the economic benefits normally attributed to competition or that would have otherwise been derived from competitive or open market forces, were assumed to be embodied in and inherent to the various processes, methods and principles of financial oversight of utility companies by regional, state and municipal regulatory authorities. Traditionally, under the various forms of regulated monopolies, a utility company, in exchange for an exclusive franchise to produce and sell electricity in a particular region, was obligated to provide an adequate supply to all consumers wanting it, at a price that was 'just and reasonable'. The determination of adequate supply and reasonable price was a matter of interpretation by utility companies and their regulators. In essence, the ultimate economic benefits, normally attributed to price equilibrium, in balance with supply, demand and other market forces, were expected to be achieved through a complex, political process of financial regulatory oversight, in which utility companies were usually reimbursed for all annual expenses or their 'cost of service' and additionally allowed to earn a 'reasonable' rate of return on plant investments. The result was often escalating electric prices, over supplies of electric capacity, by justifying unnecessarily high reserve margins based on long planning horizons (typically 20 years or greater) with extrapolated demand requirements that were generally in excess of what actually occurred over time. Although the regulatory process varied from country or country and region-to-region, the fundamental principles, which

  7. Nuclear communications and deregulated energy market

    International Nuclear Information System (INIS)

    Ruuskanen, Antti

    1998-01-01

    The electricity market a over the world is facing the most profound change ever. The market is to be deregulated, competition will be increased and companies privatised. The boom started from the UK but today the Nordic market is the most liberalised in the world. Nordic market consists of annual power sales around 350 TWh and only a modest growth potential of 12 percent per year. All fuels and all technologies meet in the marketplace. Nuclear has its good one fourth share of the production there. Nuclear is clearly for base-load with low marginal costs next to hydro electric power. There are four major players in the Nordic market. Swedish Vattenfall, IVO Group and Swedish Sydkraft are the three biggest in that order, and all of them have nuclear assets. The market is characterised by lowest power prices in Europe, two electricity exchanges and continuous power trade across the borders. The described market change from national and less open utility driven sector has clear impacts to companies strategies and consequently also to communications. All these circumstances demand, New target groups from corporate communications' point of view; new communications language to change to more business-like; new insider rules and new information practices; new business orientated journalists against a new reference group. This all opens new challenges and possibilities to re-build nuclear image. Market economy in electricity will also ease governmental nationally oriented energy policies and let market forces to decide whether investments are viable or not. This is positive for nuclear - again if and only if the power plants are managed in an economically viable way. Deregulation may open the market from political deadlock to new nuclear investments in case the above mentioned requirements are correct. All in all, market change comes sooner or later to regions not yet liberalised. It will challenge nuclear companies and their communications. The change always creates

  8. Deregulation in the electricity sector: Understanding strategic and regulatory risk

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, E.R. [City Univ. Business School, Dept. Management Systems and Information, London (United Kingdom); Bunn, D.W. [London Business School, London (United Kingdom)

    1999-08-01

    This paper is motivated by our experiences since 1990 with developing system simulation models to help UK companies in the restructured electricity industry understand the radically different market within which they must become competitive. When public utilities such as electricity have been restructured, deregulated and/or privatised, the process has often been associated with a major change in the competitive environment. As a consequence, the strategic and regulatory uncertainties ahead for these companies are unprecedented. In such a market there has been no historical evolution and all the participants including the regulatory institutions have very little understanding of how it will operate in the short term and evolve in the future. In this situation, the use of systems dynamic models appears to offer an attractive way of gaining insights into how aspects of the competitive market might evolve. In the absence of real experience and relevant analogies, learning from models assumes a key role. Such models cannot be validated empirically, but can be developed to represent how the system is designed to operate. From such a prototypical basis, sensitivity analysis can generate insights on the strategic opportunities created failings in the market design, or its potential instability to shocks and market imperfections. (au)

  9. Self-interest, deregulation and trust

    Directory of Open Access Journals (Sweden)

    Salvör Nordal

    2009-11-01

    Full Text Available In this paper I will discuss Milton Friedman’s thesis that the social responsibilityof business is to maximize the shareholders’ profit. I examine the underlyingassumption of self-interest and argue, contrary to the neoliberal thesis ofderegulation, that the profit motive must be constrained by strong state regulations.Furthermore it facilitates keeping the division between business andgovernment intact. The financial crisis shows that the emphasis on a profitmotive without the external constraints of tight regulations has serious implicationsfor the trustworthiness of business. In the latter part of the paper I willdiscuss trust in relation to self-interest. The overemphasis on self-interest isparticularly unfortunate in connection with business, and not least the financialsector, as this institution is grounded in trust, without which it cannot survive.Seen from this angle, it can be claimed that a business model, celebratingprimarily self-interest, profit-motive and deregulation, is not going to be sustainablein the long run.http://dx.doi.org/10.5324/eip.v3i2.1719

  10. The deregulation of Taiwan electricity supply industry

    International Nuclear Information System (INIS)

    Wang, K.M.

    2006-01-01

    Taiwan is on the brink of embarking on an ambitious reform in the electricity sector. The future electricity market of Taiwan will be operated under the framework set out in the Electricity Act Amendment. Independent system operator (ISO) will be the core body of the future market operations and its establishment will therefore be the key to the liberalization. This paper presents the proposed implementation plan based on diverse factors considered by the officials. A three steps phased introduction of Taiwan ISO is discussed. During the proposed Phase I interim market arrangements, Taipower's System Operation Department will assume the role of System Operator for the market. The dispatch rules are largely based on the existing Taipower internal procedure. As competition increases, the need for increased transparency will necessitate the establishment of a fully independent ISO in Phase II to provide the real time dispatch services. This will be completed within 2 years after the passage of the Electricity Act Amendment Bill. In the last phase of the deregulation process a multilateral market arrangement for managing energy imbalance and transmission constraints will result in better outcomes in relation to the policy objectives of security and economic efficiency. The 2-year timeframe stipulated in the Electricity Act Amendment Bill is a challenge for the Government and the industry. However, a smoothly functioning Taiwan ISO will bring benefits to the industry and the country in general

  11. Deregulation and Nuclear Training: Cost Effective Alternatives

    International Nuclear Information System (INIS)

    Richard P. Coe; Patricia A. Lake

    2000-01-01

    Training is crucial to the success of any organization. It is also expensive, with some estimates exceeding $50 billion annually spent on training by U.S. corporations. Nuclear training, like that of many other highly technical organizations, is both crucial and costly. It is unlikely that the amount of training can be significantly reduced. If anything, current trends indicate that training needs will probably increase as the industry and workforce ages and changes. With the advent of energy deregulation in the United States, greater pressures will surface to make the costs of energy more cost-competitive. This in turn will drive businesses to more closely examine existing costs and find ways to do things in a more cost-effective way. The commercial nuclear industry will be no exception, and nuclear training will be equally affected. It is time for nuclear training and indeed the entire nuclear industry to begin using more aggressive techniques to reduce costs. This includes the need for nuclear training to find alternatives to traditional methods for the delivery of cost-effective high-quality training that meets regulatory requirements and produces well-qualified personnel capable of working in an efficient and safe manner. Computer-based and/or Web-based training are leading emerging technologies

  12. Coal marketability: Effects of deregulation and regulation

    International Nuclear Information System (INIS)

    Attanasi, E.

    2000-01-01

    Electrical utility deregulation will force power plants to compete for sales because they will not longer have captive markets. Market uncertainty and uncertainty about future environmental regulations have encouraged power plants to shift to low sulfur coal and/or to use emissions allowances to comply with Phase 2 of the 1990 Clean Air Act Amendments. Mines in Northern and Central Appalachia and the Illinois Basin shipped 240 million tons of non-compliance coal to power plants without scrubbers in 1997. Under Phase 2, this coal will be replaced by low sulfur coal and/or be used with emission permits. It is possible that Powder River Basin coal production will have to increase by over 200 million tons/year to meet new demand. The prices of emissions permits will impose penalties on non-compliance coal that will probably drive out marginal coal producers. For example, if the cost of an emission permit is $200, coal from the Pittsburgh bed could bear a sulfur penalty of $6.55 per ton and similarly, coal from the Herrinbed could bear a penalty of $8.64 per ton

  13. Microtubule self-organisation by reaction-diffusion processes causes collective transport and organisation of cellular particles

    Directory of Open Access Journals (Sweden)

    Demongeot Jacques

    2004-06-01

    Full Text Available Abstract Background The transport of intra-cellular particles by microtubules is a major biological function. Under appropriate in vitro conditions, microtubule preparations behave as a 'complex' system and show 'emergent' phenomena. In particular, they form dissipative structures that self-organise over macroscopic distances by a combination of reaction and diffusion. Results Here, we show that self-organisation also gives rise to a collective transport of colloidal particles along a specific direction. Particles, such as polystyrene beads, chromosomes, nuclei, and vesicles are carried at speeds of several microns per minute. The process also results in the macroscopic self-organisation of these particles. After self-organisation is completed, they show the same pattern of organisation as the microtubules. Numerical simulations of a population of growing and shrinking microtubules, incorporating experimentally realistic reaction dynamics, predict self-organisation. They forecast that during self-organisation, macroscopic parallel arrays of oriented microtubules form which cross the reaction space in successive waves. Such travelling waves are capable of transporting colloidal particles. The fact that in the simulations, the aligned arrays move along the same direction and at the same speed as the particles move, suggest that this process forms the underlying mechanism for the observed transport properties. Conclusions This process constitutes a novel physical chemical mechanism by which chemical energy is converted into collective transport of colloidal particles along a given direction. Self-organisation of this type provides a new mechanism by which intra cellular particles such as chromosomes and vesicles can be displaced and simultaneously organised by microtubules. It is plausible that processes of this type occur in vivo.

  14. Microtubule self-organisation by reaction-diffusion processes causes collective transport and organisation of cellular particles

    Science.gov (United States)

    Glade, Nicolas; Demongeot, Jacques; Tabony, James

    2004-01-01

    Background The transport of intra-cellular particles by microtubules is a major biological function. Under appropriate in vitro conditions, microtubule preparations behave as a 'complex' system and show 'emergent' phenomena. In particular, they form dissipative structures that self-organise over macroscopic distances by a combination of reaction and diffusion. Results Here, we show that self-organisation also gives rise to a collective transport of colloidal particles along a specific direction. Particles, such as polystyrene beads, chromosomes, nuclei, and vesicles are carried at speeds of several microns per minute. The process also results in the macroscopic self-organisation of these particles. After self-organisation is completed, they show the same pattern of organisation as the microtubules. Numerical simulations of a population of growing and shrinking microtubules, incorporating experimentally realistic reaction dynamics, predict self-organisation. They forecast that during self-organisation, macroscopic parallel arrays of oriented microtubules form which cross the reaction space in successive waves. Such travelling waves are capable of transporting colloidal particles. The fact that in the simulations, the aligned arrays move along the same direction and at the same speed as the particles move, suggest that this process forms the underlying mechanism for the observed transport properties. Conclusions This process constitutes a novel physical chemical mechanism by which chemical energy is converted into collective transport of colloidal particles along a given direction. Self-organisation of this type provides a new mechanism by which intra cellular particles such as chromosomes and vesicles can be displaced and simultaneously organised by microtubules. It is plausible that processes of this type occur in vivo. PMID:15176973

  15. Structural insights into microtubule doublet interactions inaxonemes

    Energy Technology Data Exchange (ETDEWEB)

    Downing, Kenneth H.; Sui, Haixin

    2007-06-06

    Coordinated sliding of microtubule doublets, driven by dynein motors, produces periodic beating of the axoneme. Recent structural studies of the axoneme have used cryo-electron tomography to reveal new details of the interactions among some of the multitude of proteins that form the axoneme and regulate its movement. Connections among the several sets of dyneins, in particular, suggest ways in which their actions may be coordinated. Study of the molecular architecture of isolated doublets has provided a structural basis for understanding the doublet's mechanical properties that are related to the bending of the axoneme, and has also offered insight into its potential role in the mechanism of dynein activity regulation.

  16. Electricity deregulation - impact on gas users and markets

    International Nuclear Information System (INIS)

    Koeppel, H.

    1995-01-01

    Various scenarios for the natural gas market as a function a electricity deregulation were predicted. One scenario was the formation of an integrated market where sellers would offer a broad spectrum of energy products. This diversification would expand into the retail sector across North America. The second effect of electricity deregulation was energy cost reduction. The consumers have already been experiencing this benefit of deregulation. Cost reduction has also stimulated competition among energy suppliers, and improved suppliers' response to consumers'demands. The eventual shake-out of energy suppliers was predicted. Smaller companies that could not survive the competition would give up the market to larger companies that understood and met the customers' needs. It was concluded that deregulation of the electricity industry would have an enormous impact on the natural gas industry and that there would be opportunities for gain among buyers and sellers

  17. Efficiency and deregulation of the electricity market in Singapore

    International Nuclear Information System (INIS)

    Youngho Chang; Tuan Hin Tay

    2006-01-01

    This study examines production efficiency of electricity generation in the New Electricity Market of Singapore (NEMS), where deregulation is currently proceeding. Singapore is reliant on foreign direct investments and exports so competition from countries with lower costs such as China and India is exerting pressure on the government to reduce the costs of doing business here. Electricity cost is one of these. Deregulation is believed to be able to bring about lower electricity costs due to the various efficiency gains possible. This study concerns itself mainly with production efficiency and attempts to calculate possible production efficiency gains by using linear programming model. Production-efficiency gains are quantified by the base case scenario of continued regulation versus four counterfactual deregulation scenarios. The results indicate that cost gains could be about eight per cent of current production cost, and this is possibly a lower-bound estimate. However, whether the purported efficiency gains are realized is to be seen as the deregulation proceeds. (author)

  18. Efficiency and deregulation of the electricity market in Singapore

    International Nuclear Information System (INIS)

    Chang, Youngho; Hin Tay, Tuan

    2006-01-01

    This study examines production efficiency of electricity generation in the New Electricity Market of Singapore (NEMS), where deregulation is currently proceeding. Singapore is reliant on foreign direct investments and exports so competition from countries with lower costs such as China and India is exerting pressure on the government to reduce the costs of doing business here. Electricity cost is one of these. Deregulation is believed to be able to bring about lower electricity costs due to the various efficiency gains possible. This study concerns itself mainly with production efficiency and attempts to calculate possible production efficiency gains by using linear programming model. Production-efficiency gains are quantified by the base case scenario of continued regulation versus four counterfactual deregulation scenarios. The results indicate that cost gains could be about eight per cent of current production cost, and this is possibly a lower-bound estimate. However, whether the purported efficiency gains are realized is to be seen as the deregulation proceeds

  19. European energy markets deregulation observatory. Winter 2002/2003 period

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    Launched in 2002, the European energy markets deregulation observatory (EEMDO/OELME) aims at actualizing the main energy market indicators and at observing the advance of deregulation within the European countries. While for most of these markets, the deregulation of electricity has preceded the deregulation of gas, the natural gas market is at the evidence a key-market in Europe. For this reason, the 4. edition of the observatory (October 2003) takes into consideration for the first time the specific elements of gas markets, in addition to those of electricity markets. This article presents some excerpts of this last edition, published by Cap Gemini Ernst and Young, and synthesizes the present day situation of gas supplies and the conditions of network access by third parties. The informations reported in the EEMDO come from organizations like UCTE, Nordel, Eurelectric or from energy stock exchanges. (J.S.)

  20. Centrosome and microtubule instability in aging Drosophila cells

    Science.gov (United States)

    Schatten, H.; Chakrabarti, A.; Hedrick, J.

    1999-01-01

    Several cytoskeletal changes are associated with aging which includes alterations in muscle structure leading to muscular atrophy, and weakening of the microtubule network which affects cellular secretion and maintenance of cell shape. Weakening of the microtubule network during meiosis in aging oocytes can result in aneuploidy or trisomic zygotes with increasing maternal age. Imbalances of cytoskeletal organization can lead to disease such as Alzheimer's, muscular disorders, and cancer. Because many cytoskeletal diseases are related to age we investigated the effects of aging on microtubule organization in cell cultures of the Drosophila cell model system (Schneider S-1 and Kc23 cell lines). This cell model is increasingly being used as an alternative system to mammalian cell cultures. Drosophila cells are amenable to genetic manipulations and can be used to identify and manipulate genes which are involved in the aging processes. Immunofluorescence, scanning, and transmission electron microscopy were employed for the analysis of microtubule organizing centers (centrosomes) and microtubules at various times after subculturing cells in fresh medium. Our results reveal that centrosomes and the microtubule network becomes significantly affected in aging cells after 5 days of subculture. At 5-14 days of subculture, 1% abnormal out of 3% mitoses were noted which were clearly distinguishable from freshly subcultured control cells in which 3% of cells undergo normal mitosis with bipolar configurations. Microtubules are also affected in the midbody during cell division. The midbody in aging cells becomes up to 10 times longer when compared with midbodies in freshly subcultured cells. During interphase, microtubules are often disrupted and disorganized, which may indicate improper function related to transport of cell organelles along microtubules. These results are likely to help explain some cytoskeletal disorders and diseases related to aging.

  1. Birefringence of single and bundled microtubules.

    Science.gov (United States)

    Oldenbourg, R; Salmon, E D; Tran, P T

    1998-01-01

    We have measured the birefringence of microtubules (MTs) and of MT-based macromolecular assemblies in vitro and in living cells by using the new Pol-Scope. A single microtubule in aqueous suspension and imaged with a numerical aperture of 1.4 had a peak retardance of 0.07 nm. The peak retardance of a small bundle increased linearly with the number of MTs in the bundle. Axonemes (prepared from sea urchin sperm) had a peak retardance 20 times higher than that of single MTs, in accordance with the nine doublets and two singlets arrangement of parallel MTs in the axoneme. Measured filament retardance decreased when the filament was defocused or the numerical aperture of the imaging system was decreased. However, the retardance "area," which we defined as the image retardance integrated along a line perpendicular to the filament axis, proved to be independent of focus and of numerical aperture. These results are in good agreement with a theory that we developed for measuring retardances with imaging optics. Our theoretical concept is based on Wiener's theory of mixed dielectrics, which is well established for nonimaging applications. We extend its use to imaging systems by considering the coherence region defined by the optical set-up. Light scattered from within that region interferes coherently in the image point. The presence of a filament in the coherence region leads to a polarization dependent scattering cross section and to a finite retardance measured in the image point. Similar to resolution measurements, the linear dimension of the coherence region for retardance measurements is on the order lambda/(2 NA), where lambda is the wavelength of light and NA is the numerical aperture of the illumination and imaging lenses.

  2. Spatiotemporal relationships between growth and microtubule orientation as revealed in living root cells of Arabidopsis thaliana transformed with green-fluorescent-protein gene construct GFP-MBD

    Science.gov (United States)

    Granger, C. L.; Cyr, R. J.

    2001-01-01

    Arabidopsis thaliana plants were transformed with GFP-MBD (J. Marc et al., Plant Cell 10: 1927-1939, 1998) under the control of a constitutive (35S) or copper-inducible promoter. GFP-specific fluorescence distributions, levels, and persistence were determined and found to vary with age, tissue type, transgenic line, and individual plant. With the exception of an increased frequency of abnormal roots of 35S GFP-MBD plants grown on kanamycin-containing media, expression of GFP-MBD does not appear to affect plant phenotype. The number of leaves, branches, bolts, and siliques as well as overall height, leaf size, and seed set are similar between wild-type and transgenic plants as is the rate of root growth. Thus, we conclude that the transgenic plants can serve as a living model system in which the dynamic behavior of microtubules can be visualized. Confocal microscopy was used to simultaneously monitor growth and microtubule behavior within individual cells as they passed through the elongation zone of the Arabidopsis root. Generally, microtubules reoriented from transverse to oblique or longitudinal orientations as growth declined. Microtubule reorientation initiated at the ends of the cell did not necessarily occur simultaneously in adjacent neighboring cells and did not involve complete disintegration and repolymerization of microtubule arrays. Although growth rates correlated with microtubule reorientation, the two processes were not tightly coupled in terms of their temporal relationships, suggesting that other factor(s) may be involved in regulating both events. Additionally, microtubule orientation was more defined in cells whose growth was accelerating and less stringent in cells whose growth was decelerating, indicating that microtubule-orienting factor(s) may be sensitive to growth acceleration, rather than growth per se.

  3. Deregulation of the electric utility industry - implications for nuclear power

    International Nuclear Information System (INIS)

    Fern, A.Rose

    2000-01-01

    The deregulation movement sweeping the international electric utility community represents a dramatic shift om the traditional business model of utilities. This paper will focus on deregulation in thc United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

  4. Deregulation of the electric utility industry - implications for nuclear power

    International Nuclear Information System (INIS)

    Fern, A.R.

    2001-01-01

    The deregulation movement sweeping the international electric utility community represents a dramatic shift from the traditional utility business model. This paper will focus on deregulation in the United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

  5. Deregulating the Norwegian railway: a survey of empirical experiences abroad

    OpenAIRE

    Røstadli, Caroline

    2015-01-01

    Portraying implications of deregulation, this thesis presents an extensive review of deregulation in the European railway. It targets various decision variables concerning the introduction of competitive tendering in the rail industry. This thesis attempts to take a pragmatic stand offering an improved understanding vis-à-vis on decisions that have yet to be made, concentrating on possible competition forms, auction designs and contract designs. It offers learning points and tr...

  6. Developing products and services for a deregulated market while regulated

    International Nuclear Information System (INIS)

    Haites, E.F.

    1997-01-01

    Products and services developed for a deregulated electric power industry were discussed. The wide-ranging discussion covered products created by unbundling existing services, new products and services related to energy use, products created by expansion into communications services, and the pricing of products and services. In addition to products and services, the discussion also covered strategies for a deregulated market and the challenges of raising equity capital in a regulated environment

  7. Electricity market deregulation and its impact on the nuclear industry

    International Nuclear Information System (INIS)

    Jung, Y.E.; Alfors, G.

    2000-01-01

    Electricity has traditionally been supplied in OECD countries by state-owned facilities, or state-protected monopolies with regulated pricing. More recently, however, several countries have deregulated their electricity markets, thus opening the door to competitive supply and pricing. Deregulation of electricity markets is a trend that is expected to be followed by many countries, and can have a significant impact on the future of nuclear power programmes. (authors)

  8. Deregulation of the European Banking Industry (1980-1991)

    OpenAIRE

    Gual, Jordi; Neven, Damien J

    1992-01-01

    In this paper the experience of deregulation in the banking sector of seven EC countries (Belgium, France, Germany, Italy, the Netherlands, Spain and the UK) is analysed. Lessons are drawn for assessment of how the EC directives affecting this sector could further affect the industry. Our findings broadly confirm intuition: there is some evidence that firms in protected markets earn large rents, which are partly dissipated in excessive costs and captured by workers. Conduct deregulation seems...

  9. Curcumin alters the cytoskeleton and microtubule organization on trophozoites of Giardia lamblia.

    Science.gov (United States)

    Gutiérrez-Gutiérrez, Filiberto; Palomo-Ligas, Lissethe; Hernández-Hernández, José Manuel; Pérez-Rangel, Armando; Aguayo-Ortiz, Rodrigo; Hernández-Campos, Alicia; Castillo, Rafael; González-Pozos, Sirenia; Cortés-Zárate, Rafael; Ramírez-Herrera, Mario Alberto; Mendoza-Magaña, María Luisa; Castillo-Romero, Araceli

    2017-08-01

    Giardia lamblia is a worldwide protozoan responsible for a significant number of intestinal infections. There are several drugs for the treatment of giardiasis, but they often cause side effects. Curcumin, a component of turmeric, has antigiardial activity; however, the molecular target and mechanism of antiproliferative activity are not clear. The effects of curcumin on cellular microtubules have been widely investigated. Since tubulin is the most abundant protein in the cytoskeleton of Giardia, to elucidate whether curcumin has activity against the microtubules of this parasite, we treated trophozoites with curcumin and the cells were analyzed by scanning electron microscopy and confocal microscopy. Curcumin inhibited Giardia proliferation and adhesion in a time-concentration-dependent mode. The higher inhibitory concentrations of curcumin (3 and 15μM) disrupted the cytoskeletal structures of trophozoites; the damage was evident on the ventral disk, flagella and in the caudal region, also the membrane was affected. The immunofluorescence images showed altered distribution of tubulin staining on ventral disk and flagella. Additionally, we found that curcumin caused a clear reduction of tubulin expression. By docking analysis and molecular dynamics we showed that curcumin has a high probability to bind at the interface of the tubulin dimer close to the vinblastine binding site. All the data presented indicate that curcumin may inhibit Giardia proliferation by perturbing microtubules. Copyright © 2017. Published by Elsevier B.V.

  10. Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization.

    Science.gov (United States)

    Tanabe, Kenji

    2016-04-27

    Small-molecule compounds are widely used as biological research tools and therapeutic drugs. Therefore, uncovering novel targets of these compounds should provide insights that are valuable in both basic and clinical studies. I developed a method for image-based compound profiling by quantitating the effects of compounds on signal transduction and vesicle trafficking of epidermal growth factor receptor (EGFR). Using six signal transduction molecules and two markers of vesicle trafficking, 570 image features were obtained and subjected to multivariate analysis. Fourteen compounds that affected EGFR or its pathways were classified into four clusters, based on their phenotypic features. Surprisingly, one EGFR inhibitor (CAS 879127-07-8) was classified into the same cluster as nocodazole, a microtubule depolymerizer. In fact, this compound directly depolymerized microtubules. These results indicate that CAS 879127-07-8 could be used as a chemical probe to investigate both the EGFR pathway and microtubule dynamics. The image-based multivariate analysis developed herein has potential as a powerful tool for discovering unexpected drug properties.

  11. Effects of the KIF2C neck peptide on microtubules: lateral disintegration of microtubules and β-structure formation.

    Science.gov (United States)

    Shimizu, Youské; Shimizu, Takashi; Nara, Masayuki; Kikumoto, Mahito; Kojima, Hiroaki; Morii, Hisayuki

    2013-04-01

    Members of the kinesin-13 sub-family, including KIF2C, depolymerize microtubules. The positive charge-rich 'neck' region extending from the N-terminus of the catalytic head is considered to be important in the depolymerization activity. Chemically synthesized peptides, covering the basic region (A182-E200), induced a sigmoidal increase in the turbidity of a microtubule suspension. The increase was suppressed by salt addition or by reduction of basicity by amino acid substitutions. Electron microscopic observations revealed ring structures surrounding the microtubules at high peptide concentrations. Using the peptide A182-D218, we also detected free thin straight filaments, probably protofilaments disintegrated from microtubules. Therefore, the neck region, even without the catalytic head domain, may induce lateral disintegration of microtubules. With microtubules lacking anion-rich C-termini as a result of subtilisin treatment, addition of the peptide induced only a moderate increase in turbidity, and rings and protofilaments were rarely detected, while aggregations, also thought to be caused by lateral disintegration, were often observed in electron micrographs. Thus, the C-termini are not crucial for the action of the peptides in lateral disintegration but contribute to structural stabilization of the protofilaments. Previous structural studies indicated that the neck region of KIF2C is flexible, but our IR analysis suggests that the cation-rich region (K190-A204) forms β-structure in the presence of microtubules, which may be of significance with regard to the action of the neck region. Therefore, the neck region of KIF2C is sufficient to cause disintegration of microtubules into protofilaments, and this may contribute to the ability of KIF2C to cause depolymerization of microtubules. © 2013 The Authors Journal compilation © 2013 FEBS.

  12. Identification of interphase functions for the NIMA kinase involving microtubules and the ESCRT pathway.

    Directory of Open Access Journals (Sweden)

    Meera Govindaraghavan

    2014-03-01

    Full Text Available The Never in Mitosis A (NIMA kinase (the founding member of the Nek family of kinases has been considered a mitotic specific kinase with nuclear restricted roles in the model fungus Aspergillus nidulans. By extending to A. nidulans the results of a synthetic lethal screen performed in Saccharomyces cerevisiae using the NIMA ortholog KIN3, we identified a conserved genetic interaction between nimA and genes encoding proteins of the Endosomal Sorting Complex Required for Transport (ESCRT pathway. Absence of ESCRT pathway functions in combination with partial NIMA function causes enhanced cell growth defects, including an inability to maintain a single polarized dominant cell tip. These genetic insights suggest NIMA potentially has interphase functions in addition to its established mitotic functions at nuclei. We therefore generated endogenously GFP-tagged NIMA (NIMA-GFP which was fully functional to follow its interphase locations using live cell spinning disc 4D confocal microscopy. During interphase some NIMA-GFP locates to the tips of rapidly growing cells and, when expressed ectopically, also locates to the tips of cytoplasmic microtubules, suggestive of non-nuclear interphase functions. In support of this, perturbation of NIMA function either by ectopic overexpression or through partial inactivation results in marked cell tip growth defects with excess NIMA-GFP promoting multiple growing cell tips. Ectopic NIMA-GFP was found to locate to the plus ends of microtubules in an EB1 dependent manner, while impairing NIMA function altered the dynamic localization of EB1 and the cytoplasmic microtubule network. Together, our genetic and cell biological analyses reveal novel non-nuclear interphase functions for NIMA involving microtubules and the ESCRT pathway for normal polarized fungal cell tip growth. These insights extend the roles of NIMA both spatially and temporally and indicate that this conserved protein kinase could help integrate cell

  13. What Drives Deregulation? Economics and Politics of the Relaxation of Bank Branching Restrictions

    OpenAIRE

    Randall S. Kroszner; Philip E. Strahan

    1998-01-01

    This paper examines the key forces behind deregulation in order to assess the relative importance of alternative theories of regulatory entry and exit. We focus on bank branching deregulation across the states which began a quarter century ago and cumulated in federal deregulation in 1994. The cross-sectional and time-series variation of branching deregulation allows us to develop a hazard model to explain the timing of deregulation across the states using proxies motivated by private-interes...

  14. Lysosomes are associated with microtubules and not with intermediate filaments in cultured fibroblasts.

    OpenAIRE

    Collot, M; Louvard, D; Singer, S J

    1984-01-01

    Double immunofluorescent labeling experiments for lysosomes and either microtubules or vimentin intermediate filaments in cultured well-spread fibroblasts show a remarkable degree of superposition of the lysosomes and the microtubules. Under two different sets of conditions where the microtubules and intermediate filaments are well segregated from one another, the lysosomes remain codistributed with the microtubules. It is suggested that this specific association of lysosomes with microtubule...

  15. and its allicin on microtubule and cancer cell lines

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... microtubule protein polymer that treated by A. hirtifolium. (A), and allicin (B) in .... with a chromogenic thiol: reaction of 4-mercaptopyridine with ... transformed tumor growth in vivo by diallyl disulfide is associated with inhibition ...

  16. Effects of microtubule mechanics on hydrolysis and catastrophes

    International Nuclear Information System (INIS)

    Müller, N; Kierfeld, J

    2014-01-01

    We introduce a model for microtubule (MT) mechanics containing lateral bonds between dimers in neighboring protofilaments, bending rigidity of dimers, and repulsive interactions between protofilaments modeling steric constraints to investigate the influence of mechanical forces on hydrolysis and catastrophes. We use the allosteric dimer model, where tubulin dimers are characterized by an equilibrium bending angle, which changes from 0 ∘ to 22 ∘ by hydrolysis of a dimer. This also affects the lateral interaction and bending energies and, thus, the mechanical equilibrium state of the MT. As hydrolysis gives rise to conformational changes in dimers, mechanical forces also influence the hydrolysis rates by mechanical energy changes modulating the hydrolysis rate. The interaction via the MT mechanics then gives rise to correlation effects in the hydrolysis dynamics, which have not been taken into account before. Assuming a dominant influence of mechanical energies on hydrolysis rates, we investigate the most probable hydrolysis pathways both for vectorial and random hydrolysis. Investigating the stability with respect to lateral bond rupture, we identify initiation configurations for catastrophes along the hydrolysis pathways and values for a lateral bond rupture force. If we allow for rupturing of lateral bonds between dimers in neighboring protofilaments above this threshold force, our model exhibits avalanche-like catastrophe events. (papers)

  17. Optical properties of template synthesized nanowalled ZnS microtubules

    Science.gov (United States)

    Kumar, Rajesh; Chakarvarti, S. K.

    2007-12-01

    Electrodeposition is a versatile technique combining low processing cost with ambient conditions that can be used to prepare metallic, polymeric and semiconducting nano/micro structures. In the present work, track-etch membranes (TEMs) of makrofol (KG) have been used as templates for synthesis of ZnS nanowalled microtubules using electrodeposition technique. The morphology of the microtubules was characterized by scanning electron microscopy. Size effects on the band gap of tubules have also been studied by UV-visible spectrophotometer.

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

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    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

  19. Aggregation of SND1 in Stress Granules is Associated with the Microtubule Cytoskeleton During Heat Shock Stimulus.

    Science.gov (United States)

    Shao, Jie; Gao, Fei; Zhang, Bingbing; Zhao, Meng; Zhou, Yunli; He, Jinyan; Ren, Li; Yao, Zhi; Yang, Jie; Su, Chao; Gao, Xingjie

    2017-12-01

    Stress granules (SGs) are dynamic dense structures in the cytoplasm that form in response to a variety of environmental stress stimuli. Staphylococcal nuclease and Tudor domain containing 1 (SND1) is a type of RNA-binding protein and has been identified as a transcriptional co-activator. Our previous studies have shown that SND1 is a component of the stress granule, which forms under stress conditions. Here, we observed that SND1 granules were often surrounded by ɑ-tubulin-microtubules in 45°C-treated HeLa cells at 15 min or colocalized with microtubules at 30 or 45 min. Furthermore, Nocodazole-mediated microtubule depolymerization could significantly affect the efficient recruitment of SND1 proteins to the SGs during heat shock stress. In addition, the 45°C heat shock mediated the enhancement of eIF2α phosphorylation, which was not affected by treatment with Nocodazole, an agent that disrupts the cytoskeleton. The intact microtubule cytoskeletal tracks are important for the efficient assembly of SND1 granules under heat shock stress and may facilitate SND1 shuttling between cytoplasmic RNA foci. Anat Rec, 300:2192-2199, 2017. © 2017 The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Copyright © 2017 The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

  20. German energy policy in deregulated Europe

    International Nuclear Information System (INIS)

    Kuhnt, D.

    2000-01-01

    The author argues in favor of a more fact-oriented German energy policy: Firstly, German energy policy must accept the new European framework of a market economy. This means that German utilities must no longer be burdened with the implementation of political objectives. The German power industry needs a level playing field for competition on a European scale. Consequently, also the European partner countries should not limit themselves to the minimum conditions of the Single Market Directive in opening their markets. Secondly, German energy policy must develop new forms of cooperation with the power industry so as to maintain domestic employment and the addition of value despite considerably stronger competitive pressure. Also the conflicting targets of sustainability, continuity of supply, and economic viability must not only be discussed, but must be turned into productive approaches. Thirdly, this means that there must be no inadmissible solution in matters nuclear. If the German power industry is to remain strong, in the interest of domestic jobs and opportunities for the future, it must not lose any more domestic market share to other European companies. Fourthly, we need a new energy policy which takes cognizance of the results of market development in a more rational, less emotional way. In this respect, it should be limited henceforth to supporting renewable energies and technologies so as to enhance energy efficiency in line with market requirements. Fifthly, German energy policy must not commit the mistake of enforcing deregulation and, at the same time, exempting large segments of the market from competition. Thus, the planned expansion of renewable energies, and the increase in cogeneration to more than thirty percent of the German electricty generation, by way of quotas and revenues for electricity from these sources fed into the public grid, are incompatible with competition in Europe. The electricity tax within the framework of the eco tax, the

  1. Association of TCTP with Centrosome and Microtubules

    Directory of Open Access Journals (Sweden)

    Mariusz K. Jaglarz

    2012-01-01

    Full Text Available Translationally Controlled Tumour Protein (TCTP associates with microtubules (MT, however, the details of this association are unknown. Here we analyze the relationship of TCTP with MTs and centrosomes in Xenopus laevis and mammalian cells using immunofluorescence, tagged TCTP expression and immunoelectron microscopy. We show that TCTP associates both with MTs and centrosomes at spindle poles when detected by species-specific antibodies and by Myc-XlTCTP expression in Xenopus and mammalian cells. However, when the antibodies against XlTCTP were used in mammalian cells, TCTP was detected exclusively in the centrosomes. These results suggest that a distinct pool of TCTP may be specific for, and associate with, the centrosomes. Double labelling for TCTP and γ-tubulin with immuno-gold electron microscopy in Xenopus laevis oogonia shows localization of TCTP at the periphery of the γ-tubulin-containing pericentriolar material (PCM enveloping the centriole. TCTP localizes in the close vicinity of, but not directly on the MTs in Xenopus ovary suggesting that this association requires unidentified linker proteins. Thus, we show for the first time: (1 the association of TCTP with centrosomes, (2 peripheral localization of TCTP in relation to the centriole and the γ-tubulin-containing PCM within the centrosome, and (3 the indirect association of TCTP with MTs.

  2. Oscillatory fluid flow influences primary cilia and microtubule mechanics.

    Science.gov (United States)

    Espinha, Lina C; Hoey, David A; Fernandes, Paulo R; Rodrigues, Hélder C; Jacobs, Christopher R

    2014-07-01

    Many tissues are sensitive to mechanical stimuli; however, the mechanotransduction mechanism used by cells remains unknown in many cases. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell which extends from the basal body. The cilium is a mechanosensitive organelle and has been shown to transduce fluid flow-induced shear stress in tissues, such as the kidney and bone. The majority of microtubules assemble from the mother centriole (basal body), contributing significantly to the anchoring of the primary cilium. Several studies have attempted to quantify the number of microtubules emanating from the basal body and the results vary depending on the cell type. It has also been shown that cellular response to shear stress depends on microtubular integrity. This study hypothesizes that changing the microtubule attachment of primary cilia in response to a mechanical stimulus could change primary cilia mechanics and, possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different cell types and the microtubule attachment to the ciliary base was quantified. For the first time, an increase in microtubules around primary cilia both with time and shear rate in response to oscillatory fluid flow stimulation was demonstrated. Moreover, it is presented that the primary cilium is required for this loading-induced cellular response. This study has demonstrated a new role for the cilium in regulating alterations in the cytoplasmic microtubule network in response to mechanical stimulation, and therefore provides a new insight into how cilia may regulate its mechanics and thus the cells mechanosensitivity. Copyright © 2014 Wiley Periodicals, Inc.

  3. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    Science.gov (United States)

    Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich

    2017-01-01

    Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers. PMID:28471386

  4. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    Directory of Open Access Journals (Sweden)

    Sumadi Lukman Anwar

    2017-05-01

    Full Text Available Transposable elements (TEs comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.

  5. A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

    Science.gov (United States)

    Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

    2017-08-21

    Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Deregulation of an imprinted gene network in prostate cancer.

    Science.gov (United States)

    Ribarska, Teodora; Goering, Wolfgang; Droop, Johanna; Bastian, Klaus-Marius; Ingenwerth, Marc; Schulz, Wolfgang A

    2014-05-01

    Multiple epigenetic alterations contribute to prostate cancer progression by deregulating gene expression. Epigenetic mechanisms, especially differential DNA methylation at imprinting control regions (termed DMRs), normally ensure the exclusive expression of imprinted genes from one specific parental allele. We therefore wondered to which extent imprinted genes become deregulated in prostate cancer and, if so, whether deregulation is due to altered DNA methylation at DMRs. Therefore, we selected presumptive deregulated imprinted genes from a previously conducted in silico analysis and from the literature and analyzed their expression in prostate cancer tissues by qRT-PCR. We found significantly diminished expression of PLAGL1/ZAC1, MEG3, NDN, CDKN1C, IGF2, and H19, while LIT1 was significantly overexpressed. The PPP1R9A gene, which is imprinted in selected tissues only, was strongly overexpressed, but was expressed biallelically in benign and cancerous prostatic tissues. Expression of many of these genes was strongly correlated, suggesting co-regulation, as in an imprinted gene network (IGN) reported in mice. Deregulation of the network genes also correlated with EZH2 and HOXC6 overexpression. Pyrosequencing analysis of all relevant DMRs revealed generally stable DNA methylation between benign and cancerous prostatic tissues, but frequent hypo- and hyper-methylation was observed at the H19 DMR in both benign and cancerous tissues. Re-expression of the ZAC1 transcription factor induced H19, CDKN1C and IGF2, supporting its function as a nodal regulator of the IGN. Our results indicate that a group of imprinted genes are coordinately deregulated in prostate cancers, independently of DNA methylation changes.

  7. Direct Cytoplasmic Delivery and Nuclear Targeting Delivery of HPMA-MT Conjugates in a Microtubules Dependent Fashion.

    Science.gov (United States)

    Zhong, Jiaju; Zhu, Xi; Luo, Kui; Li, Lian; Tang, Manlin; Liu, Yanxi; Zhou, Zhou; Huang, Yuan

    2016-09-06

    As the hearts of tumor cells, the nucleus is the ultimate target of many chemotherapeutic agents and genes. However, nuclear drug delivery is always hampered by multiple intracellular obstacles, such as low efficiency of lysosome escape and insufficient nuclear trafficking. Herein, an N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-based drug delivery system was designed, which could achieve direct cytoplasmic delivery by a nonendocytic pathway and transport into the nucleus in a microtubules dependent fashion. A special targeting peptide (MT), derived from an endogenic parathyroid hormone-related protein, was conjugated to the polymer backbone, which could accumulate into the nucleus a by microtubule-mediated pathway. The in vitro studies found that low temperature and NaN3 could not influence the cell internalization of the conjugates. Besides, no obvious overlay of the conjugates with lysosome demonstrated that the polymer conjugates could enter the tumor cell cytoplasm by a nonendocytic pathway, thus avoiding the drug degradation in the lysosome. Furthermore, after suppression of the microtubule dynamics with microtubule stabilizing docetaxel (DTX) and destabilizing nocodazole (Noc), the nuclear accumulation of polymeric conjugates was significantly inhibited. Living cells fluorescence recovery after photobleaching study found that the nuclear import rate of conjugates was 2-fold faster compared with the DTX and Noc treated groups. These results demonstrated that the conjugates transported into the nucleus in a microtubules dependent way. Therefore, in addition to direct cytoplasmic delivery, our peptide conjugated polymeric platform could simultaneously mediate nuclear drug accumulation, which may open a new path for further intracellular genes/peptides delivery.

  8. Deregulation, privatisation and marketisation of Nordic comprehensive education

    DEFF Research Database (Denmark)

    Dovemark, Marianne; Kosunen, Sonja; Kauko, Jaakko

    2018-01-01

    economy. The aim of this article is to examine education in the five Nordic countries utilising three dimensions of political change: deregulation, marketisation and privatisation. We also analyse the parallel changes in relation to segregation and differentiation in education. The analysis shows...... that the themes related to deregulation seem to show fairly similar patterns and structures in all contexts. The emerging differences were discovered mainly in the themes of marketisation and privatisation. Institutional segregation emerges in all Nordic countries to different extents along the lines...

  9. Buying and selling green: deregulation and green power marketing

    International Nuclear Information System (INIS)

    Evans, Andrew

    2000-01-01

    This article discusses the increasing trend towards deregulation of electricity markets, and the driving forces for liberalisation in the EU and North America. The use of green tariffs offered by utilities to differentiate themselves from competitors and to gain and keep customers is reported, and the situation with regard to green energy within the deregulated electricity markets in Australia, the EU, Denmark, Finland, Germany, the Netherlands, Portugal, Sweden, the UK, Canada and the USA is outlined. Customers switching as a result of green tariffs, the growing role of renewables, and opportunities for the promotion of green tariffs are discussed. (UK)

  10. Quantitative Analysis of Tau-Microtubule Interaction Using FRET

    Directory of Open Access Journals (Sweden)

    Isabelle L. Di Maïo

    2014-08-01

    Full Text Available The interaction between the microtubule associated protein, tau and the microtubules is investigated. A fluorescence resonance energy transfer (FRET assay was used to determine the distance separating tau to the microtubule wall, as well as the binding parameters of the interaction. By using microtubules stabilized with Flutax-2 as donor and tau labeled with rhodamine as acceptor, a donor-to-acceptor distance of 54 ± 1 Å was found. A molecular model is proposed in which Flutax-2 is directly accessible to tau-rhodamine molecules for energy transfer. By titration, we calculated the stoichiometric dissociation constant to be equal to 1.0 ± 0.5 µM. The influence of the C-terminal tails of αβ-tubulin on the tau-microtubule interaction is presented once a procedure to form homogeneous solution of cleaved tubulin has been determined. The results indicate that the C-terminal tails of α- and β-tubulin by electrostatic effects and of recruitment seem to be involved in the binding mechanism of tau.

  11. Kinesin expands and stabilizes the GDP-microtubule lattice

    Science.gov (United States)

    Peet, Daniel R.; Burroughs, Nigel J.; Cross, Robert A.

    2018-05-01

    Kinesin-1 is a nanoscale molecular motor that walks towards the fast-growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organization of eukaryotic cells and shows great promise as a tool for nano-engineering1. Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo4, but the results are conflicting5-7 and the mechanisms are unclear. Here, we report a new dimension to the kinesin-microtubule interaction, whereby strong-binding state (adenosine triphosphate (ATP)-bound and apo) kinesin-1 motor domains inhibit the shrinkage of guanosine diphosphate (GDP) microtubules by up to two orders of magnitude and expand their lattice spacing by 1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, and so allow motile kinesins to influence the structure, stability and mechanics of their microtubule track.

  12. Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

    Science.gov (United States)

    Lu, Wen; Winding, Michael; Lakonishok, Margot; Wildonger, Jill

    2016-01-01

    Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants. PMID:27512034

  13. 75 FR 68321 - Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready...

    Science.gov (United States)

    2010-11-05

    ...] Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready Alfalfa... Inspection Service has received a supplemental request for ``partial deregulation'' from Forage Genetics... affected persons of the availability of the documents submitted to the Agency from Forage Genetics...

  14. CENTROSOMES AND MICROTUBULES DURING MEIOSIS IN THE MUSHROOM BOLETUS RUBINELLUS

    Science.gov (United States)

    McLaughlin, David J.

    1971-01-01

    The double centrosome in the basidium of Boletus rubinellus has been observed in three planes with the electron microscope at interphase preceding nuclear fusion, at prophase I, and at interphase I. It is composed of two components connected by a band-shaped middle part. At anaphase I a single, enlarged centrosome is found at the spindle pole, which is attached to the cell membrane. Microtubules mainly oriented parallel to the longitudinal axis of the basidium are present at prefusion, prophase I and interphase I. Cytoplasmic microtubules are absent when the spindle is present. The relationship of the centrosome in B. rubinellus to that in other organisms and the role of the cytoplasmic microtubules are discussed. PMID:4329156

  15. Plant cortical microtubule dynamics and cell division plane orientation

    NARCIS (Netherlands)

    Chakrabortty, Bandan

    2017-01-01

    This thesis work aimed at a better understanding of the molecular basis of oriented cell division in plant cell. As, the efficiency of plant morphogenesis depends on oriented cell division, this work should contribute towards a fundamental understanding of the molecular basis of efficient plant

  16. An Agent-based Application to Enable Deregulated Energy Markets

    NARCIS (Netherlands)

    Capodieci, Nicola; Cabri, Giacomo; Pagani, Giuliano Andrea; Aiello, Marco

    2012-01-01

    Private houses are more and more enabled with devices that can produce renewable energy, and the not so remote chance of selling the surplus energy makes them new players in the energy market. This market is likely to become deregulated since each energy home-producer can negotiate the energy price

  17. Gas prices deregulation: how to play the game well?

    International Nuclear Information System (INIS)

    Petitot, Pauline

    2014-01-01

    At the instigation of the European Union and in a context of increasing deregulation, the end of regulated gas prices in France is coming soon. Suppliers and consumers concerned are actively preparing themselves to take the turn of gas market liberalization. This short paper reveals their strategies

  18. Structural Reforms and Growth : Product and Labor Market Deregulations

    NARCIS (Netherlands)

    Eijffinger, S.C.W.; Rossi, A.

    2006-01-01

    The paper focuses on labor and product market deregulations, as fundamental elements in the passage from an investment to an innovation-based economy.The approach undertaken is prominently empirical.After a very brief description of the regulatory levels on the two sides of the Atlantic, we take two

  19. Nuclear regulation on the electrical sector's deregulation horizon

    International Nuclear Information System (INIS)

    Kindelan, J.M.

    1997-01-01

    The electrical sector is generally tending towards a deregulated system which will exert greater pressure on production costs. The author uses this article to reflect on the consequences this new conception will bring for nuclear energy and, particularly, for the activity of regulatory agencies and safety requirements. (Author)

  20. The European gaseous market deregulation and its consequences for Russia

    International Nuclear Information System (INIS)

    Finon, D.; Locatelli, C.

    2002-07-01

    Russia, the first world producer of gas in 2001 is also the main producer in the european gas market. In this framework the evolution of its gas exportations market is a major stake for the russian gas industry and for the country economy. The consequences of this gas market deregulation are analyzed in this document. (A.L.B.)

  1. Deregulation of the Nigerian economy: The theoretical milieu

    Directory of Open Access Journals (Sweden)

    Nureni Opeyemi Akintoye

    2014-01-01

    Full Text Available The deregulation of Nigerian economy was the main thrust of the Structural Adjustment Programme (SAP introduced in the country in 1986 under the leadership of General Ibrahim Babandiga (1958-1993. Prior to that period the Nigerian economy was almost a command one with wide range of government control. Indeed, the introduction of SAP was said to be a final solution to the economic crisis faced by the Country. Unfortunately, SAP was introduced yet, the economy became more crunched. During the General Abach's regime (1993­1998, SAP was suspended out rightly. When General Abdulsalami Abubakar (1998-1999 took over, he continued pursuing the privatization programme which is a synonym of deregulation of the economy with the promulgation of another privatization decree. The civilian government led by President Obasanjo which took over from 1999 made deregulation the core with vigour. It is basked on this development that this paper intends to unravel the theoretical paradigm under which the deregulation of Nigerian economy could be explained. This includes capitalism, imperialism, colonialism particularly the incorporation of Nigerian into international capitalist system.

  2. Deregulation and the Alberta experience : the implications for Ontario

    Energy Technology Data Exchange (ETDEWEB)

    Spearman, C. [Industrial Association of Southern Alberta, Lethbridge, AB (Canada)

    2002-07-01

    The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig.

  3. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Spearman, C.

    2002-01-01

    The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig

  4. Electricity pricing model in thermal generating stations under deregulation

    International Nuclear Information System (INIS)

    Reji, P.; Ashok, S.; Moideenkutty, K.M.

    2007-01-01

    In regulated public utilities with competitive power markets, deregulation has replaced the monopoly. Under the deregulated power market, the electricity price primarily depends on market mechanism and power demand. In this market, generators generally follow marginal pricing. Each generator fixes the electricity price based on their pricing strategy and it leads to more price volatility. This paper proposed a model to determine the electricity price considering all operational constraints of the plant and economic variables that influenced the price, for a thermal generating station under deregulation. The purpose of the model was to assist existing stations, investors in the power sector, regulatory authorities, transmission utilities, and new power generators in decision-making. The model could accommodate price volatility in the market and was based on performance incentive/penalty considering plant load factor, availability of the plant and peak/ off peak demand. The model was applied as a case study to a typical thermal utility in India to determine the electricity price. It was concluded that the case study of a thermal generating station in a deregulated environment showed that the electricity price mainly depended on the gross calorific value (GCV) of fuel, mode of operation, price of the fuel, and operating charges. 11 refs., 2 tabs., 1 fig

  5. Deregulation and restructuring of the electricity sector in Spain

    International Nuclear Information System (INIS)

    Francia, L.

    2000-01-01

    This economic analysis of the Electric Power industry and market in Spain shows how the electricity deregulation and liberalization in Spain have given rise to an electricity industry which not only complies in spirit and letter with the E.U. Directive on the internal energy market, but which in fact goes much further. (A.L.B.)

  6. Vulnerable Consumers in the Deregulated Dutch Health System

    NARCIS (Netherlands)

    Booltink, L.; Genugten, M.L. van; Lako, C.J.

    2015-01-01

    Public service deregulation is favoured for motivating providers to offer consumers better price-quality services. Consequently, consumers are enabled to make informed choices and choose for the best service provider. However, recent publications reveal that consumers are not capable of exercising

  7. Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles.

    Science.gov (United States)

    Decker, Franziska; Oriola, David; Dalton, Benjamin; Brugués, Jan

    2018-01-11

    Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting. © 2018, Decker et al.

  8. Regulation of microtubule nucleation mediated by gamma-tubulin complexes

    Czech Academy of Sciences Publication Activity Database

    Sulimenko, Vadym; Hájková, Zuzana; Klebanovych, Anastasiya; Dráber, Pavel

    2017-01-01

    Roč. 254, č. 3 (2017), s. 1187-1199 ISSN 0033-183X R&D Projects: GA MŠk(CZ) LD13015 Institutional support: RVO:68378050 Keywords : mitotic spindle formation * ring complex * fission yeast * organizing centers * protein complex * golgi-complex * cell-cycle * pole body * augmin * centrosome * Centrosomes * Microtubule nucleation * Microtubule-organizing centers * Non-centrosomal nucleation sites * Spindle pole bodies * gamma-Tubulin complexes Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 2.870, year: 2016

  9. Competitive positioning of power generation plants in a deregulated market

    International Nuclear Information System (INIS)

    Stephens, J.

    1998-01-01

    As industrialized countries deregulate their electric power industries, there is a fundamental shift from guaranteed cost recovery to open market competition on a deregulated grid. Utilities generally competitively bid into a power exchange where the lowest cost power providers are dispatched first. Therefore, the competitiveness of utilities determines their profitability. This commercial structure compels power generators to seek out ways of improving their equipment and plant performance. The inevitability of this trend is demonstrated by a look at the installed base in the US where the move toward deregulation is gaining momentum. More than half of the generating plants in the US are over 20 years old. The average thermal efficiency nation-wide is 33%. In contrast, contemporary coal-and gas-fired plants can operate at efficiency levels up to 45 percent and 55 to 60%, respectfully. With new facilities coming on-line, existing plants will need to make improvements to be dispatched. When deregulation fully envelopes the US market, utilities will not all fit into one pattern; their strategies and actions will depend on a multiple set of factors. Their success will be based on their ability to change landscapes from guaranteed cost recovery to competitive bidding. This paper discussers technical and commercial options available to power producers to improve their competitive positions in a deregulated market as well as software for determining the competitiveness of specific power plants and the location-based market prices of electricity. Examples of the application of alternatives will be cited along with expected payback and impact on cents per kilowatt-hour production costs

  10. Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

    NARCIS (Netherlands)

    Kosfeld, M.

    1999-01-01

    This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners

  11. The free energy profile of tubulin straight-bent conformational changes, with implications for microtubule assembly and drug discovery.

    Directory of Open Access Journals (Sweden)

    Lili X Peng

    2014-02-01

    Full Text Available αβ-tubulin dimers need to convert between a 'bent' conformation observed for free dimers in solution and a 'straight' conformation required for incorporation into the microtubule lattice. Here, we investigate the free energy landscape of αβ-tubulin using molecular dynamics simulations, emphasizing implications for models of assembly, and modulation of the conformational landscape by colchicine, a tubulin-binding drug that inhibits microtubule polymerization. Specifically, we performed molecular dynamics, potential-of-mean force simulations to obtain the free energy profile for unpolymerized GDP-bound tubulin as a function of the ∼12° intradimer rotation differentiating the straight and bent conformers. Our results predict that the unassembled GDP-tubulin heterodimer exists in a continuum of conformations ranging between straight and bent, but, in agreement with existing structural data, suggests that an intermediate bent state has a lower free energy (by ∼1 kcal/mol and thus dominates in solution. In agreement with predictions of the lattice model of microtubule assembly, lateral binding of two αβ-tubulins strongly shifts the conformational equilibrium towards the straight state, which is then ∼1 kcal/mol lower in free energy than the bent state. Finally, calculations of colchicine binding to a single αβ-tubulin dimer strongly shifts the equilibrium toward the bent states, and disfavors the straight state to the extent that it is no longer thermodynamically populated.

  12. Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization

    Energy Technology Data Exchange (ETDEWEB)

    Scaife, R.M. (Fred Hutchinson Cancer Research Center, Seattle, WA (United States)); Wilson, L. (Univ. of California, Santa Barbara (United States)); Purich, D.L. (Univ. of Florida, Gainesville (United States))

    1992-01-14

    Bovine brain microtubule protein, containing both tubulin and microtubule-associated proteins, undergoes ADP-ribosylation in the presence of ({sup 14}C)NAD{sup +} and a turkey erythrocyte mono-ADP-ribosyltransferase in vitro. The modification reaction could be demonstrated in crude brain tissue extracts where selective ADP-ribosylation of both the {alpha} and {beta} chains of tubulin and of the high molecular weight microtubule-associated protein MAP-2 occurred. In experiments with purified microtubule protein, tubulin dimer, the high molecular weight microtubule-associated protein MAP-2, and another high molecular weight microtubule-associated protein which may be a MAP-1 species were heavily labeled. Tubulin and MAP-2 incorporated ({sup 14}C)ADP-ribose to an average extent of approximately 2.4 and 30 mol of ADP-ribose/mol of protein, respectively. Assembly of microtubule protein into microtubules in vitro was inhibited by ADP-ribosylation, and incubation of assembled steady-state microtubules with ADP-ribosyltransferase and NAD{sup +} resulted in rapid depolymerization of the microtubules. Thus, the eukaryotic enzyme can ADP-ribosylate tubulin and microtubule-associated proteins to much greater extents than previously observed with cholera and pertussis toxins, and the modification can significantly modulate microtubule assembly and disassembly.

  13. Short Linear Sequence Motif LxxPTPh Targets Diverse Proteins to Growing Microtubule Ends

    NARCIS (Netherlands)

    Kumar, Anil; Manatschal, Cristina; Rai, Ankit; Grigoriev, Ilya; Degen, Miriam Steiner; Jaussi, Rolf; Kretzschmar, Ines; Prota, Andrea E; Volkmer, Rudolf; Kammerer, Richard A.; Akhmanova, Anna; Steinmetz, Michel O.

    2017-01-01

    Microtubule plus-end tracking proteins (+TIPs) are involved in virtually all microtubule-based processes. End-binding (EB) proteins are considered master regulators of +TIP interaction networks, since they autonomously track growing microtubule ends and recruit a plethora of proteins to this

  14. Prion protein inhibits microtubule assembly by inducing tubulin oligomerization

    International Nuclear Information System (INIS)

    Nieznanski, Krzysztof; Podlubnaya, Zoya A.; Nieznanska, Hanna

    2006-01-01

    A growing body of evidence points to an association of prion protein (PrP) with microtubular cytoskeleton. Recently, direct binding of PrP to tubulin has also been found. In this work, using standard light scattering measurements, sedimentation experiments, and electron microscopy, we show for First time the effect of a direct interaction between these proteins on tubulin polymerization. We demonstrate that full-length recombinant PrP induces a rapid increase in the turbidity of tubulin diluted below the critical concentration for microtubule assembly. This effect requires magnesium ions and is weakened by NaCl. Moreover, the PrP-induced light scattering structures of tubulin are cold-stable. In preparations of diluted tubulin incubated with PrP, electron microscopy revealed the presence of ∼50 nm disc-shaped structures not reported so far. These unique tubulin oligomers may form large aggregates. The effect of PrP is more pronounced under the conditions promoting microtubule formation. In these tubulin samples, PrP induces formation of the above oligomers associated with short protofilaments and sheets of protofilaments into aggregates. Noticeably, this is accompanied by a significant reduction of the number and length of microtubules. Hence, we postulate that prion protein may act as an inhibitor of microtubule assembly by inducing formation of stable tubulin oligomers

  15. Neuronal microtubule organization: from minus end to plus end

    NARCIS (Netherlands)

    Yau, K.W.

    2016-01-01

    Neurons are highly polarized cells consisting of a dendritic part and axonal part. Dendrites receive signals from other cells while axons transmit signals to other cells. In this thesis, mostly hippocampal neurons from rat embryos are used to study fundamental aspects of the microtubule organization

  16. Microtubules in cell migration, morphogenesis and metabolism: Making the connections

    NARCIS (Netherlands)

    Noordstra, I.

    2017-01-01

    Cell polarity refers to a fundamental property of eukaryotic cells, in which cellular components and structures are organized in an asymmetric fashion. In order to control their polarity, cells make use of microtubules, hollow polymers that extend throughout the cytoplasm. Due to the asymmetry of

  17. Multi-stage fuzzy PID power system automatic generation controller in deregulated environments

    International Nuclear Information System (INIS)

    Shayeghi, H.; Shayanfar, H.A.; Jalili, A.

    2006-01-01

    In this paper, a multi-stage fuzzy proportional integral derivative (PID) type controller is proposed to solve the automatic generation control (AGC) problem in a deregulated power system that operates under deregulation based on the bilateral policy scheme. In each control area, the effects of the possible contracts are treated as a set of new input signals in a modified traditional dynamical model. The multi-stage controller uses the fuzzy switch to blend a proportional derivative (PD) fuzzy logic controller with an integral fuzzy logic input. The proposed controller operates on fuzzy values passing the consequence of a prior stage on to the next stage as fact. The salient advantage of this strategy is its high insensitivity to large load changes and disturbances in the presence of plant parameter variations and system nonlinearities. This newly developed strategy leads to a flexible controller with simple structure that is easy to implement, and therefore, it can be useful for the real world power systems. The proposed method is tested on a three area power system with different contracted scenarios under various operating conditions. The results of the proposed controller are compared with those of the classical fuzzy PID type controller and classical PID controller through some performance indices to illustrate its robust performance

  18. The C-terminal region of A-kinase anchor protein 350 (AKAP350A) enables formation of microtubule-nucleation centers and interacts with pericentriolar proteins.

    Science.gov (United States)

    Kolobova, Elena; Roland, Joseph T; Lapierre, Lynne A; Williams, Janice A; Mason, Twila A; Goldenring, James R

    2017-12-15

    Microtubules in animal cells assemble (nucleate) from both the centrosome and the cis-Golgi cisternae. A-kinase anchor protein 350 kDa (AKAP350A, also called AKAP450/CG-NAP/AKAP9) is a large scaffolding protein located at both the centrosome and Golgi apparatus. Previous findings have suggested that AKAP350 is important for microtubule dynamics at both locations, but how this scaffolding protein assembles microtubule nucleation machinery is unclear. Here, we found that overexpression of the C-terminal third of AKAP350A, enhanced GFP-AKAP350A(2691-3907), induces the formation of multiple microtubule-nucleation centers (MTNCs). Nevertheless, these induced MTNCs lacked "true" centriole proteins, such as Cep135. Mapping analysis with AKAP350A truncations demonstrated that AKAP350A contains discrete regions responsible for promoting or inhibiting the formation of multiple MTNCs. Moreover, GFP-AKAP350A(2691-3907) recruited several pericentriolar proteins to MTNCs, including γ-tubulin, pericentrin, Cep68, Cep170, and Cdk5RAP2. Proteomic analysis indicated that Cdk5RAP2 and Cep170 both interact with the microtubule nucleation-promoting region of AKAP350A, whereas Cep68 interacts with the distal C-terminal AKAP350A region. Yeast two-hybrid assays established a direct interaction of Cep170 with AKAP350A. Super-resolution and deconvolution microscopy analyses were performed to define the association of AKAP350A with centrosomes, and these studies disclosed that AKAP350A spans the bridge between centrioles, co-localizing with rootletin and Cep68 in the linker region. siRNA-mediated depletion of AKAP350A caused displacement of both Cep68 and Cep170 from the centrosome. These results suggest that AKAP350A acts as a scaffold for factors involved in microtubule nucleation at the centrosome and coordinates the assembly of protein complexes associating with the intercentriolar bridge.

  19. Statistical mechanics provides novel insights into microtubule stability and mechanism of shrinkage.

    Directory of Open Access Journals (Sweden)

    Ishutesh Jain

    2015-02-01

    Full Text Available Microtubules are nano-machines that grow and shrink stochastically, making use of the coupling between chemical kinetics and mechanics of its constituent protofilaments (PFs. We investigate the stability and shrinkage of microtubules taking into account inter-protofilament interactions and bending interactions of intrinsically curved PFs. Computing the free energy as a function of PF tip position, we show that the competition between curvature energy, inter-PF interaction energy and entropy leads to a rich landscape with a series of minima that repeat over a length-scale determined by the intrinsic curvature. Computing Langevin dynamics of the tip through the landscape and accounting for depolymerization, we calculate the average unzippering and shrinkage velocities of GDP protofilaments and compare them with the experimentally known results. Our analysis predicts that the strength of the inter-PF interaction (E(s(m has to be comparable to the strength of the curvature energy (E(b(m such that E(s(m - E(b(m ≈ 1kBT, and questions the prevalent notion that unzippering results from the domination of bending energy of curved GDP PFs. Our work demonstrates how the shape of the free energy landscape is crucial in explaining the mechanism of MT shrinkage where the unzippered PFs will fluctuate in a set of partially peeled off states and subunit dissociation will reduce the length.

  20. The effect of airline deregulation on automobile fatalities.

    Science.gov (United States)

    Bylow, L F; Savage, I

    1991-10-01

    This paper attempts to quantify the effects of airline deregulation in the United States on intercity automobile travel and consequently on the number of highway fatalities. A demand model is constructed for auto travel, which includes variables representing the price and availability of air service. A reduced form model of the airline market is then estimated. Finding that deregulation has decreased airfares and increased flights, it is estimated that auto travel has been reduced by 2.2% per year on average. Given assumptions on the characteristics of drivers switching modes and the types of roads they drove on, the number of automobile fatalities averted since 1978 is estimated to be in the range 200-300 per year.

  1. Deregulation of brain insulin signaling in Alzheimer's disease.

    Science.gov (United States)

    Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

    2014-04-01

    Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

  2. Economic theory and the failure of electricity deregulation in Sweden

    International Nuclear Information System (INIS)

    Banks, F.E.

    2004-01-01

    The deregulation of electricity has failed in Sweden. Since the beginning of the deregulation 'experiment', the trend price of electricity has increased much faster than the consumer price index, especially during recent years. More importantly, because of (1) the lack of investment in domestic generating (and perhaps transmission) facilities by Swedish power companies, (2) the questionable strategy employed by these firms to mange hydroelectric reserves, (3) increased and to some extent irrational energy taxes, and (4) the beginning of nuclear 'disengagement', households and businesses are vulnerable to a prolonged 'spike' in electricity prices. Everything considered, the recent history of the Swedish electricity sector - and particularly that of the overpraised Nordic Electric Exchange (i.e. Nord Pool) - should be considered a wake-up call instead of an example. (author)

  3. Customer choice: Purchasing energy in a deregulated market

    International Nuclear Information System (INIS)

    Thumann, A.

    1999-01-01

    This book presents the detailed guidance on how to effectively purchase deregulated energy, based on first-hand reports from many of the nation's most knowledgeable experts. It is designed to provide the kind of practical advice needed by professionals who are responsible for making energy purchasing decisions. The book gives a ten-step program to guide building owners in purchasing decision making, a state-by-state retail competition update, and guidelines for buying electricity and natural gas over the worldwide web. Other topics include contract renegotiation strategies, an assessment of power pools, the role of aggregators in the energy market, real time pricing issues, where cogeneration fits within today's marketplace, and lessons learned from deregulation experiences in Scandinavia and England

  4. Revenue opportunities for gas plants arising from electricity deregulation

    International Nuclear Information System (INIS)

    Bachmann, G.C.

    1999-01-01

    A brief overview of deregulation in the electric power industry and an explanation of how these changes can be used to increase revenues of gas processing plants is provided. Deregulation in the electric power industry provides the potential to significantly reduce energy costs for the gas plant and allows technology to be applied to make a better use of a valuable commodity. Owners and operators of gas processing plants increase their operating income by taking advantage of co-generation systems which provide heat and electrical energy to the gas plant. Such an application has three revenue streams, the main one being the power sales to the gas plant, the second one heat sales, and the third increased revenues from the gas plant through a reduction of overall costs, not to mention significantly reduced downtime. Further savings are possible through diversion of excess energy produced to other facilities owned by the gas plant owner

  5. Current issues in Canadian electricity deregulation and competition

    Energy Technology Data Exchange (ETDEWEB)

    Roman, A.J. [Calgary Univ., Calgary, AB (Canada). Canadian Inst. of Resources Law

    1998-03-30

    The deregulation of the electricity industry in Canada was the main focus of this paper. In most developed countries, industries formerly dominated by a monopoly service provider have already been significantly restructured through the introduction of competition. In Canada, such restructuring has taken place only in the airline, railway, natural gas and telephone industry. In most Canadian provinces, except Alberta, electricity generation, transmission and distribution is still owned and operated by provincial and municipal governments. This report examines the present situation in electricity deregulation in Alberta, provides a summary of analysis of London Economics Inc.`s proposals and Bill 27, and presents the author`s own conclusions. A broader perspective and context is provided by references to other regulations of other industries throughout the report.

  6. Price-elastic demand in deregulated electricity markets

    OpenAIRE

    Siddiqui, Afzal S.

    2003-01-01

    The degree to which any deregulated market functions efficiently often depends on the ability of market agents to respond quickly to fluctuating conditions. Many restructured electricity markets, however, experience high prices caused by supply shortages and little demand-side response. We examine the implications for market operations when a risk-averse retailer's end-use consumers are allowed to perceive real-time variations in the electricity spot price. Using a market-equilibrium mo...

  7. Power system restructuring and deregulation: trading, performance and information technology

    International Nuclear Information System (INIS)

    Loi Lei Lai

    2001-09-01

    Representatives from several countries have contributed to a book addressing the deregulation and restructuring of the electric power industry. Articles covered include guidance on asset management, transmission balancing and meter management systems, tools for studying competitive power markets, environmental impacts, costs and benefits, and the new strategies and technology available for power generation, transmission and distribution. The book should be of interest to power systems engineers, system operators, managers, planners and policy makers in the electric power business

  8. Managing an evolution: Deregulation of the electric utility industry

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, S.K.

    1994-12-31

    The author discusses the emerging competitive situation in the electric power industry as deregulation of electric utilities looms on the horizon. The paper supports this change, and the competition it will bring, but urges caution as changes are instituted, and the regulatory bodies decide how and how much to free, and at what rates. The reason for his urge for caution comes from historical experience of other industries, which were smaller and had less direct impact on every American.

  9. Labor market deregulation and globalization: empirical evidence from OECD countries

    OpenAIRE

    Potrafke , Niklas

    2010-01-01

    Abstract This paper empirically investigates the influence of globalization on various aspects of labor market deregulation. I employ the data set by Bassanini and Duval (2006) on labor market institutions in OECD countries and the KOF index of globalization. The data set covers 20 OECD countries in the 1982?2003 period. The results suggest that globalization did neither influence the unemployment replacement rate, the unemployment benefit length, public expenditures on ALMP, the t...

  10. Competitive nuclear production on the nordic deregulated electricity market

    International Nuclear Information System (INIS)

    Bohl, T.

    2000-01-01

    The Nordic electricity market has been partly deregulated since 1994. Today only Denmark follows the timetable recommended by the European Union, while Sweden, Norway and Finland are completely deregulated. As in most countries, the production of electricity is deregulated while the distribution is still a monopoly. This deregulation of the electricity market has created a new situation for plant life management. In order to be competitive on the market it is important to cut cost down a level when the nuclear power companies earn money again. All means to cut cost have to be used while still maintaining safety and the possibilities for operation over at least 40+ years. The possibilities to invest in modernization are limited to the absolutely necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long-strategic planning. New safety requirements from the authorities have to be discussed between the industry and the authority. The requirement cost must be compared to the benefit to safety. The authority is today requested to carry out such analyses and do so in most cases. Since the electricity market is international the requirements of the authorities must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public acceptance and lobbying. Especially in Sweden a lot of effort is spent on trying to change the taxation of nuclear power. In the near future increasing electricity demand will make the prices go up to a level when nuclear power companies earn money again. The very serious worries about climate change will also strengthen the competitiveness of nuclear power. (author)

  11. Accounting for gas in a de-regulated environment

    International Nuclear Information System (INIS)

    Zawalykut, P.M.

    1992-01-01

    Since the natural gas industry was deregulated, the method of buying, selling and moving gas has changed significantly. Post-deregulation, the pipeline company moves the gas but does not acquire ownership. The full impact of deregulation is seen in opening up the market for buying and selling gas. Tracking of gas has become critical. The service customer is now buying and moving gas. The end-use customer nominates to the distribution company a quantity of gas to be transported. Responsibility is placed on the customer to estimate loads as accurately as possible to avoid possible charges. The distribution company passes the end-user nomination to the upstream transmission company, which in turn passes it along, a process that is repeated until the nomination reaches the production company. Authorizations for gas follow a similar path. The major difference between sales and service gas is the accounting and tracking. As the customer will not consume the exact amount nominated, there will be an imblance between what was nominated and metered. There will also be imbalances between what the producer places into the pipeline and what was nominated. These processes can cause administrative problems, and many customers are moving from sales to service

  12. Analysis of deregulation models; Denryoku shijo jiyuka model no bunseki

    Energy Technology Data Exchange (ETDEWEB)

    Yajima, M. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1996-04-01

    Trends toward power market deregulation were investigated in Japan and 16 other countries, and various deregulation models were examined and evaluated for their merits and demerits. There are four basic models, that is, franchise bidding model, competitive bidding in power generation model, wholesale wheeling or retail wheeling model, and mandatory pool or voluntary pool model. Power market deregulation has been a global tendency since the second half of the 1970s, with various models adopted by different countries. Out of the above-said models, it is the retail wheeling model and pool models (open access models) that allow the final customer to select power suppliers, and the number of countries adopting these models is increasing. The said models are characterized in that the disintegration of the vertical transmission-distribution integration (separation of distribution service and retail supply service) and the liberation of the retail market are simultaneously accomplished. The pool models, in particular, are enjoying favor because conditions for fair competition have already been prepared and because it is believed high in efficiency. In Japan and France, where importance is attached to atomic power generation, the competitive bidding model is adopted as a means to harmonize the introduction of competition into the source development and power generation sectors. 7 refs., 4 tabs.

  13. Inflow shortages in deregulated power markets - Reasons for concern?

    Energy Technology Data Exchange (ETDEWEB)

    Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar [Research Department, Statistics Norway, P.O. Box 8131 Dep., 0033 Oslo (Norway)

    2008-07-15

    In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply. (author)

  14. Inflow shortages in deregulated power markets - Reasons for concern?

    International Nuclear Information System (INIS)

    Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar

    2008-01-01

    In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply

  15. Retail experience in the de-regulated market

    International Nuclear Information System (INIS)

    Cummings, R.

    2003-01-01

    This paper describes the experience gained to date in the de-regulated electricity market through an examination of the commercial market. In 2001, chaos provided opportunity, while in 2002 the emphasis was on operations. In 2003, the landscape reflected hyper-competition, selling second services, and a changing landscape. A discussion followed on the residential market with a look at market structure, economics, and uncertainty concerning the future. The following components were identified as working well: wholesale market, commercial market, market model/data, and innovation in offerings and green supply. Areas requiring further improvement were also identified. It was suggested that the residential de-regulated roadmap should be clarified and retail friendly transactions should be imposed. Other improvements involve education and operations/system capabilities. The author concluded that the deregulated electricity market is still an immature market, where progress is being made in the commercial market. The residential market is in a critical period, with a market model still evolving. figs

  16. Cycles in deregulated electricity markets: Empirical evidence from two decades

    International Nuclear Information System (INIS)

    Arango, Santiago; Larsen, Erik

    2011-01-01

    In this article, we discuss the 'cycle hypothesis' in electricity generation, which states that the introduction of deregulation in an electricity system might lead to sustained fluctuations of over- and under-capacity. The occurrence of cycles is one of the major threats for electricity markets as it affects the security of supply, and creates uncertainty in both the profitability of electricity companies and in consumer prices. We discuss the background for these cycles using analogies with other capital-intensive industries, along with evidence from the analysis of behavioral simulation models as well as from experimental electricity markets. Using data from the oldest deregulated markets we find support for the hypothesis in the case of the English and Chilean markets, based on an autocorrelation analysis. Evidence from the Nordpool market is more ambiguous, although we might be observing the first half of a cycle in generation capacity. Comparing a simulation of the English market performed in 1992 with the actual performance we can observe that the qualitative behavior of the model is consistent with the actual evolution. Finally, we discuss possible mechanisms for damping cycles in electricity generation, such as mothballing, capacity payments, and reliability markets. - Research highlights: → We explore the emergence of cycles in the electricity generation capacity after deregulation. → We discuss the reason for cycles in generation capacity and compare different theories. → Analysis of England and Chile data show strong indications that cycles have emerged.

  17. Choice of electricity provider in California after deregulation

    Science.gov (United States)

    Keanini, Rasa Ilze

    Surveys often ask consumers how much they are willing to pay for certain goods and services, without requiring the consumer to actually pay for the good or service. Such surveys, termed stated preference studies, find that consumers value renewable electricity. This result is in contrast to actual experiences in recently deregulated electricity markets in several states, including California. When given the opportunity to choose in California, only one to two percent of the population opted for renewable electricity products. This dissertation used data from residential customers who chose an alternative electricity product in California's deregulated electricity market to determine the value placed on the renewable attribute of electricity products. This dissertation begins by taking a historical look at the electricity market of the nation and specifically California. From 1998 through 2001, California's electricity market was deregulated to include retail competition. This dissertation used data from electric service providers to reveal the factors influencing residential customer's choice of electricity product. Discrete choice models were used to determine the factors influencing electricity product choice. The results indicated that both price and renewable content had an effect on choice of product. Additionally, a more complicated model jointly estimating the discrete choice of electricity product with the continuous choice of electricity consumption (kWh) was specified and estimated.

  18. Tubulation of Class II MHC Compartments Is Microtubule Dependent and Involves Multiple Endolysosomal Membrane Proteins in Primary Dendritic Cells1

    Science.gov (United States)

    Vyas, Jatin M.; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J. Christopher; Van der Veen, Annemarthe G.; Ploegh, Hidde L.

    2009-01-01

    Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. PMID:17513769

  19. The neurosteroid pregnenolone reverts microtubule derangement induced by the loss of a functional CDKL5-IQGAP1 complex.

    Science.gov (United States)

    Barbiero, Isabella; Peroni, Diana; Tramarin, Marco; Chandola, Chetan; Rusconi, Laura; Landsberger, Nicoletta; Kilstrup-Nielsen, Charlotte

    2017-09-15

    CDKL5 is a protein kinase that plays a key role for neuronal functions as testified by the onset of complex neuronal dysfunctions in patients with genetic lesions in CDKL5. Here we identify a novel interactor of CDKL5, IQGAP1, a fundamental regulator of cell migration and polarity. In accordance with a functional role of this interaction, depletion of CDKL5 impairs cell migration and impedes the localization of IQGAP1 at the leading edge. Moreover, we demonstrate that CDKL5 is required for IQGAP1 to form a functional complex with its effectors, Rac1 and the microtubule plus end tracking protein CLIP170. These defects eventually impact on the microtubule association of CLIP170, thus deranging their dynamics. CLIP170 is a cellular target of the neurosteroid pregnenolone; by blocking CLIP170 in its active conformation, pregnenolone is capable of restoring the microtubule association of CLIP170 in CDKL5 deficient cells and rescuing morphological defects in neurons devoid of CDKL5. These findings provide novel insights into CDKL5 functions and pave the way for target-specific therapeutic strategies for individuals affected with CDKL5-disorder. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells.

    Science.gov (United States)

    Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J Christopher; Van der Veen, Annemarthe G; Ploegh, Hidde L

    2007-06-01

    Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.

  1. The nucleation of microtubules in Aspergillus nidulans germlings

    Directory of Open Access Journals (Sweden)

    Cristina de Andrade-Monteiro

    1999-09-01

    Full Text Available Microtubules are filaments composed of dimers of alpha- and beta-tubulins, which have a variety of functions in living cells. In fungi, the spindle pole bodies usually have been considered to be microtubule-organizing centers. We used the antimicrotubule drug Benomyl in block/release experiments to depolymerize and repolymerize microtubules in Aspergillus nidulans germlings to learn more about the microtubule nucleation process in this filamentous fungus. Twenty seconds after release from Benomyl short microtubules were formed from several bright (immunofluorescent dots distributed along the germlings, suggesting that microtubule nucleation is randomly distributed in A. nidulans germlings. Since nuclear movement is dependent on microtubules in A. nidulans we analyzed whether mutants defective in nuclear distribution along the growing hyphae (nud mutants have some obvious microtubule defect. Cytoplasmic, astral and spindle microtubules were present and appeared to be normal in all nud mutants. However, significant changes in the percentage of short versus long mitotic spindles were observed in nud mutants. This suggests that some of the nuclei of nud mutants do not reach the late stage of cell division at normal temperatures.Microtúbulos são filamentos compostos por dímeros das tubulinas a e b e têm uma variedade de funções nas células vivas. Em fungos, os corpúsculos polares dos fusos são geralmente considerados os centros organizadores dos microtúbulos. Com o objetivo de contribuir para uma melhor compreensão dos processos de nucleação dos microtúbulos no fungo filamentoso A. nidulans, nós utilizamos a droga antimicrotúbulo Benomil em experimentos de bloqueio e liberação para depolimerizar e repolimerizar os microtúbulos. Após 20 segundos de reincubação em meio sem Benomil, pequenos microtúbulos foram formados a partir de pontos distribuídos pela célula, sugerindo que os pontos de nucleação de microtúbulos s

  2. Heuristic consequences of a load of oxygen in microtubules.

    Science.gov (United States)

    Denis, Pierre A

    2014-04-01

    The current cell oxygen paradigm shows some major gaps that have not yet been resolved. Something seems to be lacking for the comprehensive statement of the oxygen distribution in the cell, especially the low cytoplasmic oxygen level. The entrapment of oxygen in microtubules (MTs) resolves the latter observation, as well as the occurrence of an extensive cytoplasmic foam formation. It leads to a novel oxygen paradigm for cells. During the steady-state treadmilling, the mobile cavity would absorb oxygenated cytoplasm forward, entrap gas nuclei and concentrate them. A fluorescence method is described to confirm the in vitro load of oxygen in MTs during their periodic growths and shrinkages. The latter operating mechanism is called the gas dynamic instability (GDI) of MTs. Several known biosystems could rest on the GDI. (1) The GTP-cap is linked with the gas meniscus encountered in a tube filled with gas. The GTP hydrolysis is linked to the conformational change of the GTPase domain according to the bubble pressure, and to the shaking of protofilaments with gas particles (soliton-like waves). (2) The GDI provides a free energy water pump because water molecules have to escape from MT pores when foam concentrates within the MT. Beside ATP hydrolysis in motor proteins, the GDI provides an additional driving force in intracellular transport of cargo. The water streams flowing from the MT through slits organize themselves as water layers between the cargo and the MT surface, and break ionic bridges. It makes the cargo glide over a water rail. (3) The GDI provides a universal motor for chromosome segregation because the depolymerization of kinetochorial MTs is expected to generate a strong cytoplasmic foam. Chromosomes are sucked up according to the pressure difference (or density difference) applied to opposite sides of the kinetochore, which is in agreement with Archimedes' principle of buoyancy. Non-kinetochorial MTs reabsorb foam during GDI. Last, the mitotic spindle

  3. TCTEX1D4, a novel protein phosphatase 1 interactor: connecting the phosphatase to the microtubule network

    Science.gov (United States)

    Korrodi-Gregório, Luís; Vieira, Sandra I.; Esteves, Sara L. C.; Silva, Joana V.; Freitas, Maria João; Brauns, Ann-Kristin; Luers, Georg; Abrantes, Joana; Esteves, Pedro J.; da Cruz e Silva, Odete A. B.; Fardilha, Margarida; da Cruz e Silva, Edgar F.

    2013-01-01

    Summary Reversible phosphorylation plays an important role as a mechanism of intracellular control in eukaryotes. PPP1, a major eukaryotic Ser/Thr-protein phosphatase, acquires its specificity by interacting with different protein regulators, also known as PPP1 interacting proteins (PIPs). In the present work we characterized a physiologically relevant PIP in testis. Using a yeast two-hybrid screen with a human testis cDNA library, we identified a novel PIP of PPP1CC2 isoform, the T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) that has recently been described as a Tctex1 dynein light chain family member. The overlay assays confirm that TCTEX1D4 interacts with the different spliced isoforms of PPP1CC. Also, the binding domain occurs in the N-terminus, where a consensus PPP1 binding motif (PPP1BM) RVSF is present. The distribution of TCTEX1D4 in testis suggests its involvement in distinct functions, such as TGFβ signaling at the blood–testis barrier and acrosome cap formation. Immunofluorescence in human ejaculated sperm shows that TCTEX1D4 is present in the flagellum and in the acrosome region of the head. Moreover, TCTEX1D4 and PPP1 co-localize in the microtubule organizing center (MTOC) and microtubules in cell cultures. Importantly, the TCTEX1D4 PPP1BM seems to be relevant for complex formation, for PPP1 retention in the MTOC and movement along microtubules. These novel results open new avenues to possible roles of this dynein, together with PPP1. In essence TCTEX1D4/PPP1C complex appears to be involved in microtubule dynamics, sperm motility, acrosome reaction and in the regulation of the blood–testis barrier. PMID:23789093

  4. Modulation of microtubule assembly by the HIV-1 Tat protein is strongly dependent on zinc binding to Tat

    Directory of Open Access Journals (Sweden)

    Muller Sylviane

    2008-07-01

    Full Text Available Abstract Background During HIV-1 infection, the Tat protein plays a key role by transactivating the transcription of the HIV-1 proviral DNA. In addition, Tat induces apoptosis of non-infected T lymphocytes, leading to a massive loss of immune competence. This apoptosis is notably mediated by the interaction of Tat with microtubules, which are dynamic components essential for cell structure and division. Tat binds two Zn2+ ions through its conserved cysteine-rich region in vitro, but the role of zinc in the structure and properties of Tat is still controversial. Results To investigate the role of zinc, we first characterized Tat apo- and holo-forms by fluorescence correlation spectroscopy and time-resolved fluorescence spectroscopy. Both of the Tat forms are monomeric and poorly folded but differ by local conformational changes in the vicinity of the cysteine-rich region. The interaction of the two Tat forms with tubulin dimers and microtubules was monitored by analytical ultracentrifugation, turbidity measurements and electron microscopy. At 20°C, both of the Tat forms bind tubulin dimers, but only the holo-Tat was found to form discrete complexes. At 37°C, both forms promoted the nucleation and increased the elongation rates of tubulin assembly. However, only the holo-Tat increased the amount of microtubules, decreased the tubulin critical concentration, and stabilized the microtubules. In contrast, apo-Tat induced a large amount of tubulin aggregates. Conclusion Our data suggest that holo-Tat corresponds to the active form, responsible for the Tat-mediated apoptosis.

  5. Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

    International Nuclear Information System (INIS)

    Tseng, P.C.

    1998-01-01

    As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc

  6. Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, P.C.

    1998-07-01

    As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc.

  7. A study on the deregulation of the Finnish electricity markets

    International Nuclear Information System (INIS)

    Kopsakangas-Savolainen, M.

    2002-01-01

    Governments have regarded the electricity industry as a leading industrial sector throughout the history. Because of its strategic importance to industrial development, its impacts on the social and environmental issues and its natural monopoly characteristics, it has been seen necessary to regulate electricity industry effectively. However, in the mid 1980s it was realised that even though transmission and distribution networks are natural monopolies, the scale economies in electricity production at the generating unit level had exhausted at a unit size of about 500 MW. This meant that supply and generation had become potentially competitive activities. In Finland the new Electricity Market Act (EMA) came into force in 1.11.1995. According to it the production and supply of electricity became deregulated and competition was introduced to the industry. The main aim of the law was to improve efficiency. This dissertation analyses, both theoretically and empirically, the impacts of deregulation to the Finnish electricity markets. In chapter two we discuss on the grounds and incentives of the deregulation processes that have been carried out in different countries. We also determine the crucial factors in order succeed in the deregulation process. According to our view the success depend on the number of active players in the wholesale market, the rules of the bidding procedure, the organisation of the demand side operation, the neutrality of transmission grid, the structure of production technologies and the ownership structure of the industry. In chapter three we theoretically model the profit maximising behaviour of the Finnish electricity companies based on different stages of vertical integration and on different stage of competition. According to our results the profit maximising pricing rules of distribution units is dependent on the stage of integration and on the stage of competition. The separated distribution company maximises profits by setting the

  8. The road to electricity deregulation : open highway or crash-test dummy

    Energy Technology Data Exchange (ETDEWEB)

    Laughlin, K. [PJM Interconnection LLC, Norristown, PA (United States)

    2001-07-01

    An overview of PJM Interconnection company operations and governance was presented. The company has been a member of the power pool since 1927 and has been ISO approved by the Federal Energy Regulatory Commission (FERC) since January 1998. PJM operates 540 generating units with a total generation capacity of 57,000 MW. Its role as a marketer since deregulation of energy markets has proven to be a success due to its dynamic operation through independent efficiency. Charts depicting real time evolution of PJM's competitive markets were included. In 2000, PJM administered market transactions with a value of about $2.3 billion. The company's energy market was composed of 52 per cent bilateral transactions, 18 per cent spot market, 27 per cent self-supplied, and 3 per cent net imports. tabs., figs.

  9. TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Aoife T Heaslip

    Full Text Available The microtubule cytoskeleton provides essential structural support for all eukaryotic cells and can be assembled into various higher order structures that perform drastically different functions. Understanding how microtubule-containing assemblies are built in a spatially and temporally controlled manner is therefore fundamental to understanding cell physiology. Toxoplasma gondii, a protozoan parasite, contains at least five distinct tubulin-containing structures, the spindle pole, centrioles, cortical microtubules, the conoid, and the intra-conoid microtubules. How these five structurally and functionally distinct sets of tubulin containing structures are constructed and maintained in the same cell is an intriguing problem. Previously, we performed a proteomic analysis of the T. gondii apical complex, a cytoskeletal complex located at the apical end of the parasite that is composed of the conoid, three ring-like structures, and the two short intra-conoid microtubules. Here we report the characterization of one of the proteins identified in that analysis, TgICMAP1. We show that TgICMAP1 is a novel microtubule binding protein that can directly bind to microtubules in vitro and stabilizes microtubules when ectopically expressed in mammalian cells. Interestingly, in T. gondii, TgICMAP1 preferentially binds to the intra-conoid microtubules, providing us the first molecular tool to investigate the intra-conoid microtubule assembly process during daughter construction.

  10. Vibrations of microtubules: Physics that has not met biology yet

    Czech Academy of Sciences Publication Activity Database

    Kučera, Ondřej; Havelka, Daniel; Cifra, Michal

    2017-01-01

    Roč. 72, 1 July (2017), s. 13-22 ISSN 0165-2125 R&D Projects: GA ČR(CZ) GA15-17102S Grant - others:AV ČR(CZ) SAV-15-22 Program:Bilaterální spolupráce Institutional support: RVO:67985882 Keywords : Models * Vibrations * Microtubules Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 1.575, year: 2016

  11. TIP maker and TIP marker; EB1 as a master controller of microtubule plus ends.

    Science.gov (United States)

    Vaughan, Kevin T

    2005-10-24

    The EB1 protein is a member of the exciting and enigmatic family of microtubule (MT) tip-tracking proteins. EB1 acts as an exquisite marker of dynamic MT plus ends in some cases, whereas in others EB1 is thought to directly dictate the behavior of the plus ends. How EB1 differentiates between these two roles remains unclear; however, a growing list of interactions between EB1 and other MT binding proteins suggests there may be a single mechanism. Adding another layer of complexity to these interactions, two studies published in this issue implicate EB1 in cross-talk between mitotic MTs and between MTs and actin filaments (Goshima et al., p. 229; Wu et al., p. 201). These results raise the possibility that EB1 is a central player in MT-based transport, and that the activity of MT-binding proteins depends on their ability or inability to interact with EB1.

  12. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    Directory of Open Access Journals (Sweden)

    Yi-sheng Li

    2016-01-01

    Full Text Available GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

  13. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  14. Bank CEO Pay-Performance Relations and the Effects of Deregulation.

    OpenAIRE

    Crawford, Anthony J; Ezzell, John R; Miles, James A

    1995-01-01

    The authors test the deregulation hypothesis that posits that bank CEO compensation became more sensitive to performance as bank management became less regulated. They observe a significant increase in pay-performance sensitivities from their 1976-81 regulation subsample to their 1982-88 deregulation subsample. These increases in pay sensitivities after deregulation are observed for salary and bonus, stock options, and common stock holdings. The authors observe increases in the pay-performanc...

  15. Product Market Deregulation and Employment Outcomes: Evidence from the German Retail Sector

    OpenAIRE

    Charlotte Senftleben-König

    2014-01-01

    This paper investigates the short- and medium-term effects of the deregulation of shopopening hours legislation on retail employment in Germany. In 2006, the legislative competence was shifted from the federal to the state level, leading to a gradual deregulation of shop opening restrictions in most of Germany’s sixteen federal states. The paper exploits regional variation in the legislation in order to identify the effect product market deregulation has on retail employment. We find robust...

  16. Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

    OpenAIRE

    Kosfeld, M.

    1999-01-01

    This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners and customers, and second, the ‘solution’ to this problem depends on the specific cost structure of stores and the preferences of customers. In particular, it may happen that, even if extended shoppi...

  17. The German Political Economy Between Deregulation and Re-regulation: Party Discourses on Minimum Wage Policies

    OpenAIRE

    Dostal, Jörg Michael

    2012-01-01

    In the German political economy of the early 21st century, labor market policymaking has shifted toward deregulation and liberalization. In particular, the so-called Hartz labor market reforms of the Social Democratic Party and Green Party government, introduced in 2002 and 2003, pushed for employment growth in low-wage and deregulated employment sectors. This article focuses on one of the key debates triggered by Germany’s labor market deregulation after 2002, namely whethe...

  18. Power systems locational marginal pricing in deregulated markets

    Science.gov (United States)

    Wang, Hui-Fung Francis

    Since the beginning of the 1990s, the electricity business is transforming from a vertical integrating business to a competitive market operations. The generation, transmission, distribution subsystem of an electricity utility are operated independently as Genco (generation subsystem), Transco (transmission subsystem), and Distco (distribution subsystem). This trend promotes more economical inter- and intra regional transactions to be made by the participating companies and the users of electricity to achieve the intended objectives of deregulation. There are various types of electricity markets that are implemented in the North America in the past few years. However, transmission congestion management becomes a key issue in the electricity market design as more bilateral transactions are traded across long distances competing for scarce transmission resources. It directly alters the traditional concept of energy pricing and impacts the bottom line, revenue and cost of electricity, of both suppliers and buyers. In this research, transmission congestion problem in a deregulated market environment is elucidated by implementing by the Locational Marginal Pricing (LMP) method. With a comprehensive understanding of the LMP method, new mathematical tools will aid electric utilities in exploring new business opportunities are developed and presented in this dissertation. The dissertation focuses on the development of concept of (LMP) forecasting and its implication to the market participants in deregulated market. Specifically, we explore methods of developing fast LMP calculation techniques that are differ from existing LMPs. We also explore and document the usefulness of the proposed LMP in determining electricity pricing of a large scale power system. The developed mathematical tools use of well-known optimization techniques such as linear programming that are support by several flow charts. The fast and practical security constrained unit commitment methods are the

  19. Deregulation and pricing in a hydro electric system

    International Nuclear Information System (INIS)

    Stoea, P.; Livik, K.; Wangensteen, I.

    1992-01-01

    In line with the current development in some European countries, notably the UK and the Netherlands, deregulation and market competition has been introduced in Norwegian electricity supply in order to improve the economic efficiency of the system. The legal basis for the introduction is the new Norwegian Energy Act that was approved in the Storting (parliament) in June 1990 and came legally into effect on January 1, 1991. This paper deals with the organizational structure, the price formation in the wholesale market, and the tariffs and metering equipment that are being developed to meet the needs of the customers and the utilities in this new situation. (author)

  20. A congestion line flow control in deregulated power system

    Directory of Open Access Journals (Sweden)

    Venkatarajan Shanmuga Sundaram

    2011-01-01

    Full Text Available Under open access, market-driven transactions have become the new independent decision variables defining the behavior of the power system. The possibility of transmission lines getting over-loaded is relatively more under deregulated operation because different parts of the system are owned by separate companies and in part operated under varying service charges. This paper discusses a two-tier algorithm for correcting the lone overloads in conjunction with the conventional power-flow methods. The method uses line flow sensitivities, which are computed by the East Decoupled Power-flow algorithm and can be adapted for on-line implementation.

  1. Regulation of developmental and environmental signaling by interaction between microtubules and membranes in plant cells

    Directory of Open Access Journals (Sweden)

    Qun Zhang

    2015-12-01

    Full Text Available ABSTRACT Cell division and expansion require the ordered arrangement of microtubules, which are subject to spatial and temporal modifications by developmental and environmental factors. Understanding how signals translate to changes in cortical microtubule organization is of fundamental importance. A defining feature of the cortical microtubule array is its association with the plasma membrane; modules of the plasma membrane are thought to play important roles in the mediation of microtubule organization. In this review, we highlight advances in research on the regulation of cortical microtubule organization by membrane-associated and membrane-tethered proteins and lipids in response to phytohormones and stress. The transmembrane kinase receptor Rho-like guanosine triphosphatase, phospholipase D, phosphatidic acid, and phosphoinositides are discussed with a focus on their roles in microtubule organization.

  2. Simultaneous 3D tracking of passive tracers and microtubule bundles in an active gel

    Science.gov (United States)

    Fan, Yi; Breuer, Kenneth S.; Fluids Team

    Kinesin-driven microtubule bundles generate a spontaneous flow in unconfined geometries. They exhibit properties of active matter, including the emergence of collective motion, reduction of apparent viscosity and consumption of local energy. Here we present results from 3D tracking of passive tracers (using Airy rings and 3D scanning) synchronized with 3D measurement of the microtubule bundles motion. This technique is applied to measure viscosity variation and collective flow in a confined geometry with particular attention paid to the self-pumping system recently reported by Wu et al. (2016). Results show that the viscosity in an equilibrium microtubule network is around half that of the isotropic unbundled microtubule solution. Cross-correlations of the active microtubule network and passive tracers define a neighborhood around microtubule bundles in which passive tracers are effectively transported. MRSEC NSF.

  3. Linking cortical microtubule attachment and exocytosis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ivar Noordstra

    2017-04-01

    Full Text Available Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex. In this review, we focus on mammalian protein complexes that have been shown to participate in both cortical microtubule capture and exocytosis, thereby regulating the spatial organization of secretion. These complexes include microtubule plus-end tracking proteins, scaffolding factors, actin-binding proteins, and components of vesicle docking machinery, which together allow efficient coordination of cargo transport and release.

  4. Measuring and modeling polymer concentration profiles near spindle boundaries argues that spindle microtubules regulate their own nucleation

    Science.gov (United States)

    Kaye, Bryan; Stiehl, Olivia; Foster, Peter J.; Shelley, Michael J.; Needleman, Daniel J.; Fürthauer, Sebastian

    2018-05-01

    Spindles are self-organized microtubule-based structures that segregate chromosomes during cell division. The mass of the spindle is controlled by the balance between microtubule turnover and nucleation. The mechanisms that control the spatial regulation of microtubule nucleation remain poorly understood. While previous work found that microtubule nucleators bind to pre-existing microtubules in the spindle, it is still unclear whether this binding regulates the activity of those nucleators. Here we use a combination of experiments and mathematical modeling to investigate this issue. We measured the concentration of microtubules and soluble tubulin in and around the spindle. We found a very sharp decay in the concentration of microtubules at the spindle interface. This is inconsistent with a model in which the activity of nucleators is independent of their association with microtubules but consistent with a model in which microtubule nucleators are only active when bound to pre-existing microtubules. This argues that the activity of microtubule nucleators is greatly enhanced when bound to pre-existing microtubules. Thus, microtubule nucleators are both localized and activated by the microtubules they generate.

  5. The Nightmare of the Leader: The Impact of Deregulation on an Oligopoly Insurance Market

    OpenAIRE

    Jennifer L. Wang; Larry Y. Tzeng; En-Lin Wang

    2003-01-01

    This paper explores the impact of deregulation of licensing on an oligopoly insurance market. We show that deregulation of licensing in a Stackelberg-type oligopoly market may not have any impact on the leader’s output if the number of firms increases but the market structure remains. On the other hand, if the market structure is reorganized because of the deregulation of licensing, the leader’s output could be significantly reduced after deregulation. By using the unique data of the insuranc...

  6. Ase1p Organizes Antiparallel Microtubule Arrays during Interphase and Mitosis in Fission YeastV⃞

    OpenAIRE

    Loïodice, Isabelle; Staub, Jayme; Setty, Thanuja Gangi; Nguyen, Nam-Phuong T.; Paoletti, Anne; Tran, P. T.

    2005-01-01

    Proper microtubule organization is essential for cellular processes such as organelle positioning during interphase and spindle formation during mitosis. The fission yeast Schizosaccharomyces pombe presents a good model for understanding microtubule organization. We identify fission yeast ase1p, a member of the conserved ASE1/PRC1/MAP65 family of microtubule bundling proteins, which functions in organizing the spindle midzone during mitosis. Using fluorescence live cell imaging, we show that ...

  7. A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules

    International Nuclear Information System (INIS)

    Iimori, Makoto; Ozaki, Kanako; Chikashige, Yuji; Habu, Toshiyuki; Hiraoka, Yasushi; Maki, Takahisa; Hayashi, Ikuko; Obuse, Chikashi; Matsumoto, Tomohiro

    2012-01-01

    Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+ TIP). We have generated a mutation (89R) replacing glutamine with arginine in the calponin homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed that the mutation confers a higher affinity to microtubules and enhances the intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no longer a + TIP, but binds strongly the microtubule lattice. Live cell imaging has revealed that while the wild type Mal3 proteins dissociate from the tip of the growing microtubules before the onset of shrinkage, the mutant Mal3 proteins persist on microtubules and reduces a rate of shrinkage after a longer pausing period. Consequently, the mutant Mal3 proteins cause abnormal elongation of microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster of serine/threonine residues in the linker connecting the CH and EB1-like C-terminal motif domains. The phosphorylation occurs in a microtubule-dependent manner and reduces the affinity of Mal3 to microtubules. We propose that because the 89R mutation is resistant to the effect of phosphorylation, it can associate persistently with microtubules and confers a stronger stability of microtubules likely by reinforcing the cylindrical structure. -- Highlights: ► We characterize a mutation (mal3-89R) in fission yeast homolog of EB1. ► The mutation enhances the activity to assemble microtubules. ► Mal3 is phosphorylated in a microtubule-dependent manner. ► The phosphorylation negatively regulates the Mal3 activity.

  8. A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules

    Energy Technology Data Exchange (ETDEWEB)

    Iimori, Makoto; Ozaki, Kanako [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Chikashige, Yuji [Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe, 651-2492 (Japan); Habu, Toshiyuki [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto, 606-8501 (Japan); Hiraoka, Yasushi [Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe, 651-2492 (Japan); Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871 (Japan); Maki, Takahisa; Hayashi, Ikuko [Graduate School of Nanobioscience, Yokohama City University, Tsurumi, Yokohama, 230-0045 (Japan); Obuse, Chikashi [Graduate School of Life Science, Hokkaido University, Sapporo 001-0021 (Japan); Matsumoto, Tomohiro, E-mail: tmatsumo@house.rbc.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto, 606-8501 (Japan)

    2012-02-01

    Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+ TIP). We have generated a mutation (89R) replacing glutamine with arginine in the calponin homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed that the mutation confers a higher affinity to microtubules and enhances the intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no longer a + TIP, but binds strongly the microtubule lattice. Live cell imaging has revealed that while the wild type Mal3 proteins dissociate from the tip of the growing microtubules before the onset of shrinkage, the mutant Mal3 proteins persist on microtubules and reduces a rate of shrinkage after a longer pausing period. Consequently, the mutant Mal3 proteins cause abnormal elongation of microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster of serine/threonine residues in the linker connecting the CH and EB1-like C-terminal motif domains. The phosphorylation occurs in a microtubule-dependent manner and reduces the affinity of Mal3 to microtubules. We propose that because the 89R mutation is resistant to the effect of phosphorylation, it can associate persistently with microtubules and confers a stronger stability of microtubules likely by reinforcing the cylindrical structure. -- Highlights: Black-Right-Pointing-Pointer We characterize a mutation (mal3-89R) in fission yeast homolog of EB1. Black-Right-Pointing-Pointer The mutation enhances the activity to assemble microtubules. Black-Right-Pointing-Pointer Mal3 is phosphorylated in a microtubule-dependent manner. Black-Right-Pointing-Pointer The phosphorylation negatively regulates the Mal3 activity.

  9. Combing and self-assembly phenomena in dry films of Taxol-stabilized microtubules

    Directory of Open Access Journals (Sweden)

    Rose Franck

    2007-01-01

    Full Text Available AbstractMicrotubules are filamentous proteins that act as a substrate for the translocation of motor proteins. As such, they may be envisioned as a scaffold for the self-assembly of functional materials and devices. Physisorption, self-assembly and combing are here investigated as a potential prelude to microtubule-templated self-assembly. Dense films of self-assembled microtubules were successfully produced, as well as patterns of both dendritic and non-dendritic bundles of microtubules. They are presented in the present paper and the mechanism of their formation is discussed.

  10. Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation

    OpenAIRE

    Hori, Akiko; Ikebe, Chiho; Tada, Masazumi; Toda, Takashi

    2014-01-01

    Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator ?-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity....

  11. Tracking of plus-ends reveals microtubule functional diversity in different cell types

    Science.gov (United States)

    Shaebani, M. Reza; Pasula, Aravind; Ott, Albrecht; Santen, Ludger

    2016-07-01

    Many cellular processes are tightly connected to the dynamics of microtubules (MTs). While in neuronal axons MTs mainly regulate intracellular trafficking, they participate in cytoskeleton reorganization in many other eukaryotic cells, enabling the cell to efficiently adapt to changes in the environment. We show that the functional differences of MTs in different cell types and regions is reflected in the dynamic properties of MT tips. Using plus-end tracking proteins EB1 to monitor growing MT plus-ends, we show that MT dynamics and life cycle in axons of human neurons significantly differ from that of fibroblast cells. The density of plus-ends, as well as the rescue and catastrophe frequencies increase while the growth rate decreases toward the fibroblast cell margin. This results in a rather stable filamentous network structure and maintains the connection between nucleus and membrane. In contrast, plus-ends are uniformly distributed along the axons and exhibit diverse polymerization run times and spatially homogeneous rescue and catastrophe frequencies, leading to MT segments of various lengths. The probability distributions of the excursion length of polymerization and the MT length both follow nearly exponential tails, in agreement with the analytical predictions of a two-state model of MT dynamics.

  12. Today or not today: Deregulating the Russian gas sector

    International Nuclear Information System (INIS)

    Grigoryev, Yuli

    2007-01-01

    Although Russia is the world's biggest producer of natural gas, its ability to maintain timely and reliable supply to meet the growing global demand has come under question in recent months. The gas war with Ukraine notwithstanding, concern has been raised by a number of observers that underinvestment in the gas sector will lead to a systemic failure of the state monopolist OAO Gazprom to increase or even maintain current levels of production. Yet with a quarter of European gas coming from Russia, and with increasing presence of Gazprom in European downstream operations (such as Germany, Hungary, and other CIS states) as well as seemingly closer ties with Algeria, another major supplier of gas to Europe, there has been a strong reaction from Europe's policy-makers to decrease dependence on Russian gas. Deregulating and liberalising the gas sector would see the lifting of restrictions to foreign or independent investors wishing to gain access to Russian reserves, as well as the unhindered access to the pipeline infrastructure and export markets. It would also signal the unbundling of Gazprom and an end to the artificially low price of gas to the domestic consumer. This paper discusses whether deregulation is the optimal way to raise capital, attract investment and increase supply security for Russia's Western neighbours. In doing so, the paper identifies the objectives of the EU as the importer whilst trying to align them with the objectives of the Russian Federation as the exporter, in the current political context

  13. A novel approach for modeling deregulated electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Ofir D., E-mail: rubino@agri.huji.ac.i [Department of Agricultural Economics and Management, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Babcock, Bruce A., E-mail: babcock@iastate.ed [Department of Economics, Iowa State University, 578F Heady Hall, Ames, IA 50011-1070 (United States); Center for Agricultural and Rural Development (CARD), Iowa State University, Ames, IA 50011-1070 (United States)

    2011-05-15

    The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: {yields} The state of knowledge regarding modeling electricity markets is incomplete. {yields} Electricity forward premiums are not necessarily driven by risk aversion. {yields} Efficiency in production requires a certain premium for forward contracting. {yields} It is likely that market premiums are substantially higher than their optimal level. {yields} Policy regulation should not seek to eliminate forward premium entirely.

  14. A novel approach for modeling deregulated electricity markets

    International Nuclear Information System (INIS)

    Rubin, Ofir D.; Babcock, Bruce A.

    2011-01-01

    The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: → The state of knowledge regarding modeling electricity markets is incomplete. → Electricity forward premiums are not necessarily driven by risk aversion. → Efficiency in production requires a certain premium for forward contracting. → It is likely that market premiums are substantially higher than their optimal level. → Policy regulation should not seek to eliminate forward premium entirely.

  15. Bluewater Power goes ERP route to address deregulation : case study

    Energy Technology Data Exchange (ETDEWEB)

    Broad, K. [Bluewater Power Distribution Corp., Sarnia, ON (Canada)

    2009-05-15

    Bluewater Power Distribution Corporation distributes electricity to 35,000 customers in southwestern Ontario, including residential customers, large industries and commercial establishments. Their distribution system network consists of more than 344 miles of overhead wires and 125 miles of underground wires. The company employs more than 90 full-time people and is the result of a merger of six local utilities in year 2000. Ontario's energy market was preparing to deregulate at the time of the merger. Under the deregulation rules, utilities in the province were required to provide unbundled bills and exchange customer electronic business transactions with energy retailers. New rules opened up the cost of power on the wholesale side, requiring utilities to conduct wholesale settlements with the Independent Electricity System Operator (IESO). The IESO manages Ontario's bulk electricity power system and operates the wholesale market. This article described the solution that Bluewater Power's information technology (IT) team found to support Ontario's local market, meet regulatory demands and adapt to future regulatory changes.

  16. Productivity growth and deregulation of Japanese electricity distribution

    International Nuclear Information System (INIS)

    Goto, Mika; Sueyoshi, Toshiyuki

    2009-01-01

    Deregulation of Japanese electric power industry began in 1995. After the amendment of Electricity Utility Industry Law in 1995, competition was partially introduced in a generation sector and retail competition started from 2000. Eligibility to choose suppliers was gradually extended from larger to smaller customers. As of 2008, almost all customers except households can choose their electricity suppliers. Based upon both previous implementation result of competition policy and review on their achievement, Japanese government will begin new policy debate in 2013 to assess further retail competition which includes household customers. To prepare for policy suggestion on the future electric power industry, this study examines the cost structure of Japanese electricity distribution. For the purpose, we estimate a multi-product translog cost function of Japanese electricity distribution from 1983 to 2003. Using the estimated cost function, we calculate several economic measures such as productivity growth, technical change and economies of scale and scope. The empirical results of this study indicate the improvement in productivity growth after deregulation.

  17. Effect of demand management on regulated and deregulated electricity sectors

    International Nuclear Information System (INIS)

    Fahrioglu, Murat

    2016-01-01

    Our society derives a quantifiable benefit from electric power. In particular, forced outages or blackouts have enormous consequences on society, one of which is loss of economic surplus. The society relies on having a continuous supply of electrical energy. Some customers may willingly risk this continuous supply and participate in demand management programs for electrical power. If the power system grid is in trouble, electric utilities need to have demand relief. Customers willing to reduce their demand to help the system can receive an incentive fee for helping the utilities. Demand relief can be system wide or location specific. Sometimes it can be more effective to fix the electrical demand vs. supply imbalance from the demand side. The value of demand management contracts is greatly affected by customer location. Inclusion of locational attributes into the contract design procedure increases the effectiveness of the contracts by helping a utility get more value from its demand management programs. Independent System Operators and regulators, among others, can also benefit from effective demand management. This paper will investigate how this type of demand management contracts can help the electricity sector both in regulated and deregulated environments. - Highlights: • Demand management can help prevent forced electricity outages. • Both electric utilities and ISOs can use demand management. • Regulated and deregulated electricity sectors can benefit from demand management. • Demand management contracts can be effectively used in power system grids.

  18. Competition and deregulation in electricity : the national and continental dimension

    International Nuclear Information System (INIS)

    Garant, D.

    2000-01-01

    Some of the recent developments with Hydro-Quebec in terms of moving towards a deregulated competitive market were presented. In June 2000, the Quebec National Assembly passed legislation allowing for power generation and wholesale supply of electricity within Quebec will to be a deregulated business based on the gradual introduction of a competitive, contested market at the wholesale level. This legislation mitigates Hydro-Quebec's market power by legislating a long term fixed price supply contract between Hydro-Quebec's generation and distribution groups, operating as a functionally separate division within corporate Hydro-Quebec. Hydro-Quebec's market power in generation is 36,000 MW, the bulk of which will be committed to the Quebec distribution market at a fixed price of about 2.8 cents per kWh. Hydro-Quebec will maintain the rights to develop large scale hydro in Quebec if the development meets conditions of economic viability, environmental soundness and is locally acceptable. Hydro-Quebec is also expanding into new areas of generation such as wind power. The electric utility also believes it can play a role in Atlantic Canada by trading and moving off-peak and on-peak energy by using the storage capacity of their large hydro reservoirs

  19. The impact of deregulation on the US nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Baratta, A.J. [Pennsylvania State Univ., Nuclear Safety Center, University Park, PA (United States)

    2001-07-01

    In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

  20. Generation capacity adequacy in deregulated markets : options for Alberta

    International Nuclear Information System (INIS)

    Ayres, M.

    2004-01-01

    The Canadian Energy Research Institute (CERI) is a Calgary-based non-profit organization that conducts studies on energy and related environmental issues to help Canadian business and government organizations. This paper summarized the information in a two volume CERI study report which assessed generation capacity issues in deregulated electricity markets in Canada. The study observed the restructuring experience in several jurisdictions and described how, or if, energy-only markets are succeeding in ensuring capacity additions. Supply-side and demand-side mechanisms have been proposed as solutions to address these problems. Theoretical and practical issues of adequacy that are most relevant from a Canadian perspective were presented. In fully developed energy markets, the price of energy reflects scarcity. When generating resources are abundant prices are low. Since investment decisions are based on price expectations, it is unlikely that deregulated markets in their current state can offer adequate generation for the long term. It was concluded that long-term investment will occur with competitive markets and by adding a capacity mechanism to the market design. tabs., figs

  1. Deregulation and internationalisation - impact on the Swedish nuclear industry

    International Nuclear Information System (INIS)

    Haukeland, Sverre R.

    2010-01-01

    The deregulation of the Swedish electricity market in 1996 was well known in advance, and the nuclear power plants in Sweden, as well as their main suppliers, made early preparations for a this new situation. In a study - performed by the author at Malardalen University in Sweden - it is concluded that the electricity industry, including the nuclear power plants, was fundamentally transformed in conjunction with market liberalisation. Two large foreign companies, E-on and Fortum, entered the Swedish market and became part-owners of the nuclear plants. After deregulation, the electricity market in Sweden is dominated by these two companies and the large national company Vattenfall. Similarly, Vattenfall has recently grown into an international energy company, acquiring generation capacity in Northern Europe outside of Sweden, including nuclear power plants in Germany. Restructuring of the nuclear industry on the supplier side started in the 1980's, when the Swedish company ASEA and BBC of Switzerland merged to become ABB. Several years later the Swedish nuclear plant supplier ABB-Atom became part of Westinghouse Electric Company, today owned by Toshiba. The Swedish experience thus confirms an international trend of mergers and consolidation in the nuclear industry. (authors)

  2. Electricity deregulation, spot price patterns and demand-side management

    International Nuclear Information System (INIS)

    Li, Y.; Flynn, P.C.

    2006-01-01

    This paper examines extensive hourly or half-hourly power price data from 14 deregulated power markets. It analyzes average diurnal patterns, relationship to system load, volatility, and consistency over time. Diurnal patterns indicate the average price spread between off-peak and on-peak and weekend vs. weekday power consumption. Volatility is measured by price velocity: the average normalized hourly change in power price, calculated daily. The calculated price velocity is broken down into an expected component that arises from the diurnal pattern and an unexpected component that arises from unknown factors. The analysis reveals significant differences among markets, suggesting that demand-side management (DSM) of power consumption is far more difficult in some markets than in others. At one extreme, Spain, Britain and Scandinavia show consistent diurnal price patterns, a stable relationship between price and system load, and a low unexplained component of price volatility. A power consumer in these markets could form a reasonable expectation of a reward for DSM of elective power consumption. At the other extreme, two markets in Australia show erratic diurnal price patterns from year to year, low correlation between price and system load, and a high amount of unexpected price velocity. A power consumer in these markets would have far greater difficulty in realizing a benefit from DSM. Markets that experienced one period of very high prices without a clear external cause, such as California and Alberta, appear to have a significant longer-term erosion of public support for deregulation. (author)

  3. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Desrochers, J.P.

    2002-01-01

    An overview of the first year of electric power industry deregulation in Alberta was presented. The way in which electricity is bought and sold in Ontario and throughout North America is changing. Costs are no longer fixed and regulated. Electricity is becoming a commodity with high levels of price volatility. The paper presented hedging options for Alberta consumers, contracting lessons, market issues and lessons for Ontario. A comparison of Alberta's deregulation schedule with that of Ontario's was included. One year after market opening in Alberta, power prices have dropped significantly. There is a greater than expected demand side response, increased development in power generation, and a decrease in natural gas prices. Issues that still need to be addressed in Alberta include billing and load settlement issues, invoicing/billing standards, the lack of competition at the retail level, and future balancing of pool charges. Energy Advantage Inc. (EA) does not foresee the same drastic increase in price as seen in Alberta market opening, but suggests that uncertainty and volatility will exist in Ontario. In Alberta, customers who did nothing and stayed on default were the ones who benefited, but took a great risk. EA suggests that customers must understand how and when they use electricity, how much is used during on- and off-peak hours, and in the summer versus the winter. When electricity is priced hourly, it is important to know consumption patterns. 7 figs

  4. The impact of deregulation on the US nuclear industry

    International Nuclear Information System (INIS)

    Baratta, A.J.

    2001-01-01

    In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

  5. Maintenance cost models in deregulated power systems under opportunity costs

    International Nuclear Information System (INIS)

    Al-Arfaj, K.; Dahal, K.; Azaiez, M.N.

    2007-01-01

    In a centralized power system, the operator is responsible for scheduling maintenance. There are different types of maintenance, including corrective maintenance; predictive maintenance; preventive maintenance; and reliability-centred maintenance. The main cause of power failures is poor maintenance. As such, maintenance costs play a significant role in deregulated power systems. They include direct costs associated with material and labor costs as well as indirect costs associated with spare parts inventory, shipment, test equipment, indirect labor, opportunity costs and cost of failure. In maintenance scheduling and planning, the cost function is the only component of the objective function. This paper presented the results of a study in which different components of maintenance costs were modeled. The maintenance models were formulated as an optimization problem with single and multiple objectives and a set of constraints. The maintenance costs models could be used to schedule the maintenance activities of power generators more accurately and to identify the best maintenance strategies over a period of time as they consider failure and opportunity costs in a deregulated environment. 32 refs., 4 tabs., 4 figs

  6. Electric utilities deregulation and its impact on nuclear power generating stations

    International Nuclear Information System (INIS)

    Trehan, N.K.

    1998-01-01

    Under restructuring and deregulation, it is not clear as to who would have the responsibility, and what obligations the market participants would have to ensure that the electrical system reliability (stability) is maintained. Due to the dynamic nature of the electrical grid, especially with the implementation of restructuring and deregulation, vulnerabilities exist which may impact the reliability (stability) of the offsite electrical power system. In a nuclear power generating unit, an offsite electric power system and an onsite electric power system are required to permit the functioning of structures, systems, and components which are important to safety. The safety function for each system is to provide sufficient capacity and capability to assure that the containment integrity is maintained during power operation or in the event of a postulated accident. Analyses performed by the applicants must verify that the electrical grid remains stable in the event of a loss of the nuclear unit generator, the largest other unit on the grid or the most critical transmission line. The stability of the electric grid is assumed in the safety analyses and a change in it would impact those analyses. However, it may impact the availability of a stable electric power to the safety buses because of the limited number of available transmission lines. This paper discusses electrical power generation and demand, reserve margins, power transfer capability, development of new innovative technologies to compensate for lack of the construction of transmission lines, legislation for the formulation of a self regulation organization (SRO), grid disturbances that may lead to a voltage collapse, and the vulnerabilities which may impact the availability of a stable power to the nuclear power generating stations

  7. Cdk1-Cyclin B1-mediated Phosphorylation of Tumor-associated Microtubule-associated Protein/Cytoskeleton-associated Protein 2 in Mitosis*

    OpenAIRE

    Uk Hong, Kyung; Kim, Hyun-Jun; Kim, Hyo-Sil; Seong, Yeon-Sun; Hong, Kyeong-Man; Bae, Chang-Dae; Park, Joobae

    2009-01-01

    During mitosis, establishment of structurally and functionally sound bipolar spindles is necessary for maintaining the fidelity of chromosome segregation. Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton-associated protein 2 (CKAP2), is a mitotic spindle-associated protein whose level is frequently up-regulated in various malignancies. Previous reports have suggested that TMAP is a potential regulator of mitotic spindle assembly and dynamics and that it is re...

  8. Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability.

    Directory of Open Access Journals (Sweden)

    Yusuke Mori

    Full Text Available The centrosomal protein, CDK5RAP2, is a microcephaly protein that regulates centrosomal maturation by recruitment of a γ-tubulin ring complex (γ-TuRC onto centrosomes. In this report, we identified a novel human centrosomal protein, Cep169, as a binding partner of CDK5RAP2, a member of microtubule plus-end-tracking proteins (+TIPs. Cep169 interacts directly with CDK5RAP2 through CM1, an evolutionarily conserved domain, and colocalizes at the pericentriolar matrix (PCM around centrioles with CDK5RAP2. In addition, Cep169 interacts with EB1 through SxIP-motif responsible for EB1 binding, and colocalizes with CDK5RAP2 at the microtubule plus-end. EB1-binding-deficient Cep169 abolishes EB1 interaction and microtubule plus-end attachment, indicating Cep169 as a novel member of +TIPs. We further show that ectopic expression of either Cep169 or CDK5RAP2 induces microtubule bundling and acetylation in U2OS cells, and depletion of Cep169 induces microtubule depolymerization in HeLa cells, although Cep169 is not required for assembly of γ-tubulin onto centrosome by CDK5RAP2. These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2.

  9. TRESK background K(+ channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Gabriella Braun

    Full Text Available TRESK (TWIK-related spinal cord K(+ channel, KCNK18 is a major background K(+ channel of sensory neurons. Dominant-negative mutation of TRESK is linked to familial migraine. This important two-pore domain K(+ channel is uniquely activated by calcineurin. The calcium/calmodulin-dependent protein phosphatase directly binds to the channel and activates TRESK current several-fold in Xenopus oocytes and HEK293 cells. We have recently shown that the kinase, which is responsible for the basal inhibition of the K(+ current, is sensitive to the adaptor protein 14-3-3. Therefore we have examined the effect of the 14-3-3-inhibited PAR-1/MARK, microtubule-associated-protein/microtubule affinity-regulating kinase on TRESK in the Xenopus oocyte expression system. MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium-dependent activation. Several other serine-threonine kinase types, generally involved in the modulation of other ion channels, failed to influence TRESK current recovery. MARK2 phosphorylated the primary determinant of regulation, the cluster of three adjacent serine residues (S274, 276 and 279 in the intracellular loop of mouse TRESK. In contrast, serine 264, the 14-3-3-binding site of TRESK, was not phosphorylated by the kinase. Thus MARK2 selectively inhibits TRESK activity via the S274/276/279 cluster, but does not affect the direct recruitment of 14-3-3 to the channel. TRESK is the first example of an ion channel phosphorylated by the dynamically membrane-localized MARK kinases, also known as general determinants of cellular polarity. These results raise the possibility that microtubule dynamics is coupled to the regulation of excitability in the neurons, which express TRESK background potassium channel.

  10. Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

    Directory of Open Access Journals (Sweden)

    Richard C Wang

    Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

  11. GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation.

    Science.gov (United States)

    Černohorská, Markéta; Sulimenko, Vadym; Hájková, Zuzana; Sulimenko, Tetyana; Sládková, Vladimíra; Vinopal, Stanislav; Dráberová, Eduarda; Dráber, Pavel

    2016-06-01

    Microtubule nucleation from γ-tubulin complexes, located at the centrosome, is an essential step in the formation of the microtubule cytoskeleton. However, the signaling mechanisms that regulate microtubule nucleation in interphase cells are largely unknown. In this study, we report that γ-tubulin is in complexes containing G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (βPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) in various cell lines. Immunofluorescence microscopy revealed association of GIT1, βPIX and activated PAK1 with centrosomes. Microtubule regrowth experiments showed that depletion of βPIX stimulated microtubule nucleation, while depletion of GIT1 or PAK1 resulted in decreased nucleation in the interphase cells. These data were confirmed for GIT1 and βPIX by phenotypic rescue experiments, and counting of new microtubules emanating from centrosomes during the microtubule regrowth. The importance of PAK1 for microtubule nucleation was corroborated by the inhibition of its kinase activity with IPA-3 inhibitor. GIT1 with PAK1 thus represent positive regulators, and βPIX is a negative regulator of microtubule nucleation from the interphase centrosomes. The regulatory roles of GIT1, βPIX and PAK1 in microtubule nucleation correlated with recruitment of γ-tubulin to the centrosome. Furthermore, in vitro kinase assays showed that GIT1 and βPIX, but not γ-tubulin, serve as substrates for PAK1. Finally, direct interaction of γ-tubulin with the C-terminal domain of βPIX and the N-terminal domain of GIT1, which targets this protein to the centrosome, was determined by pull-down experiments. We propose that GIT1/βPIX signaling proteins with PAK1 kinase represent a novel regulatory mechanism of microtubule nucleation in interphase cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Katanin localization requires triplet microtubules in Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Jessica M Esparza

    Full Text Available Centrioles and basal bodies are essential for a variety of cellular processes that include the recruitment of proteins to these structures for both centrosomal and ciliary function. This recruitment is compromised when centriole/basal body assembly is defective. Mutations that cause basal body assembly defects confer supersensitivity to Taxol. These include bld2, bld10, bld12, uni3, vfl1, vfl2, and vfl3. Flagellar motility mutants do not confer sensitivity with the exception of mutations in the p60 (pf19 and p80 (pf15 subunits of the microtubule severing protein katanin. We have identified additional pf15 and bld2 (ε-tubulin alleles in screens for Taxol sensitivity. Null pf15 and bld2 alleles are viable and are not essential genes in Chlamydomonas. Analysis of double mutant strains with the pf15-3 and bld2-6 null alleles suggests that basal bodies in Chlamydomonas may recruit additional proteins beyond katanin that affect spindle microtubule stability. The bld2-5 allele is a hypomorphic allele and its phenotype is modulated by nutritional cues. Basal bodies in bld2-5 cells are missing proximal ends. The basal body mutants show aberrant localization of an epitope-tagged p80 subunit of katanin. Unlike IFT proteins, katanin p80 does not localize to the transition fibers of the basal bodies based on an analysis of the uni1 mutant as well as the lack of colocalization of katanin p80 with IFT74. We suggest that the triplet microtubules are likely to play a key role in katanin p80 recruitment to the basal body of Chlamydomonas rather than the transition fibers that are needed for IFT localization.

  13. Interaction of microtubules with active principles of Xanthium strumarium.

    Science.gov (United States)

    Menon, G S; Kuchroo, K; Dasgupta, D

    2001-01-01

    Indigenous variety of Xanthium strumarium (X. strumarium) was screened for its antimitotic activity using the microtubule-tubulin system isolated from mammalian tissue. A preliminary phytochemical screening of the whole extracts of the plant was carried out followed by partial purification of the whole extract of X.strumarium. The separated fractions obtained were identified and used for in vitro polymerization studies. The whole as well as partially separated chemical constituents of X. strumarium showed effective inhibition of tubulin polymerization. The results thus suggest that X. strumarium may possess antimitotic components.

  14. Genetic analysis of a Drosophila microtubule-associated protein

    OpenAIRE

    1992-01-01

    The 205-kD microtubule-associated protein (205K MAP) is one of the principal MAPs in Drosophila. 205K MAP is similar to the HeLa 210K/MAP4 family of MAPs since it shares the following biochemical properties: it is present in several isoforms, has a molecular mass of approximately 200 kD, and is thermostable. Furthermore, immuno-crossreactivity has been observed between mouse MAP4, HeLa 210K, and Drosophila 205K MAP. Currently, there is little information concerning the biological function of ...

  15. Air pollution effects due to deregulation of the electric industry

    Science.gov (United States)

    Davoodi, Khojasteh Riaz

    The Energy Policy Act of 1992 introduced the concept of open-access into the electric utility industry which allows privately-owned utilities to transmit power produced by non-utility generators and independent power producers (IPPs). In April 1996, the Federal Energy Regulatory Commission (FERC) laid down the final rules (Orders No. 888 & No. 889), which required utilities to open their transmission lines to any power producer and charge them no more than what they pay for the use of their own lines. These rules set the stage for the retail sale of electricity to industrial, commercial and residential utility customers; non-utility generators (Nugs); and power marketers. These statutory, regulatory and administrative changes create for the electric utility industry two different forces that contradict each other. The first is the concept of competition among utility companies; this places a greater emphasis on electric power generation cost control and affects generation/fuel mix selection and demand side management (DSM) activities. The second force, which is converse to the first, is that utilities are major contributors to the air pollution burden in the United States and environmental concerns are forcing them to reduce emissions of air pollutants by using more environmentally friendly fuels and implementing energy saving programs. This study evaluates the impact of deregulation within the investor owned electric utilities and how this deregulation effects air quality by investigating the trend in demand side management programs and generation/fuel mix. A survey was conducted of investor owned utilities and independent power producers. The results of the survey were analyzed by analysis of variance and regression analysis to determine the impact to Air Pollution. An air Quality Impact model was also developed in this study. This model consists of six modules: (1) demand side management and (2) consumption of coal, (3) gas, (4) renewable, (5) oil and (6

  16. Core designs for the de-regulated market

    International Nuclear Information System (INIS)

    Almberger, J.; Bernro, R.; Pettersson, H.

    1999-01-01

    Complete text of publication follows: The electricity market deregulation in the Nordic countries encourages innovations and cost reductions for power production in the Vattenfall reactors. The competition on the electricity market is strong, electricity price reductions dramatic and uncertainties about the future power demand is large. In the fuel area this situation has given increased attention to traditional areas like flexibility in power production, improved core designs, need for margins (improved fuel designs), improved surveillance, decreased lead times. At Vattenfall new fuel designs are already being implemented following the last fuel purchase, for which flexibility and margins, were given high values in the evaluations with the multipurpose task of eliminating fuel related problems and meeting the future market situation. This strategy has given Vattenfall a flying start to meeting the demands of the de-regulated market. What has been added are broad studies undertaken to investigate the various route into the future with respect to finding the most effective strategies for fuel and core design and optimization. In the present paper the Vattenfall priorities for fuel designs and margins are presented in a schematic manner summarizing the results of the last fuel purchase and also presenting the current program for LFAs. Technical limitations, licensing and R and D aspects, with respect to improving the fuel utilization will be mentioned. The main focus in the paper is on the broad study carried out in the PWR core design area. Driven by the relatively low power demand various possibilities for higher production flexibility have been investigated specifically extended coast-down, coast-up and yearly load follow. Further to reduce the costs for fuel consumption improvements in core designs have been studied: improved low leakage loading patterns, low enriched end zones, improved Gd designs etc. Main results and conclusions of the core design studies will

  17. Ionic wave propagation and collision in an excitable circuit model of microtubules

    Science.gov (United States)

    Guemkam Ghomsi, P.; Tameh Berinyoh, J. T.; Moukam Kakmeni, F. M.

    2018-02-01

    In this paper, we report the propensity to excitability of the internal structure of cellular microtubules, modelled as a relatively large one-dimensional spatial array of electrical units with nonlinear resistive features. We propose a model mimicking the dynamics of a large set of such intracellular dynamical entities as an excitable medium. We show that the behavior of such lattices can be described by a complex Ginzburg-Landau equation, which admits several wave solutions, including the plane waves paradigm. A stability analysis of the plane waves solutions of our dynamical system is conducted both analytically and numerically. It is observed that perturbed plane waves will always evolve toward promoting the generation of localized periodic waves trains. These modes include both stationary and travelling spatial excitations. They encompass, on one hand, localized structures such as solitary waves embracing bright solitons, dark solitons, and bisolitonic impulses with head-on collisions phenomena, and on the other hand, the appearance of both spatially homogeneous and spatially inhomogeneous stationary patterns. This ability exhibited by our array of proteinic elements to display several states of excitability exposes their stunning biological and physical complexity and is of high relevance in the description of the developmental and informative processes occurring on the subcellular scale.

  18. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

    Science.gov (United States)

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-03-23

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

  19. Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide.

    Science.gov (United States)

    Rösner, H; Williams, L A; Jung, A; Kraus, W

    2001-08-22

    Dibenzyl trisulphide (DTS), a main lipophilic compound in Petiveria alliacea L. (Phytolaccaceae), was identified as one of the active immunomodulatory compounds in extracts of the plant. To learn more about its biological activities and molecular mechanisms, we conducted one-dimensional NMR interaction studies with bovine serum albumin (BSA) and tested DTS and related compounds in two well-established neuronal cell-and-tissue culture systems. We found that DTS preferentially binds to an aromatic region of BSA which is rich in tyrosyl residues. In SH-SY5Y neuroblastoma cells, DTS attenuates the dephosphorylation of tyrosyl residues of MAP kinase (erk1/erk2). In the same neuroblastoma cell line and in Wistar 38 human lung fibroblasts, DTS causes a reversible disassembly of microtubules, but it did not affect actin dynamics. Probably due to the disruption of the microtubule dynamics, DTS also inhibits neuroblastoma cell proliferation and neurite outgrowth from spinal cord explants. Related dibenzyl compounds with none, one, or two sulphur atoms were found to be significantly less effective. These data confirmed that the natural compound DTS has a diverse spectrum of biological properties, including cytostatic and neurotoxic actions in addition to immunomodulatory activities.

  20. Power plant operation and management in a deregulated market

    Energy Technology Data Exchange (ETDEWEB)

    Carraretto, Cristian [Department of Mechanical Engineering, University of Padova, Via Venezia, 1-35131 Padova (Italy)

    2006-05-15

    This paper analyzes the influence of electricity deregulation on the design, operation and management of the power plants owned by strategic and non-strategic producers. After a sensitivity analysis aimed at finding market conditions of profitable operation for thermal and hydroelectric power plants, a Nash-equilibrium market model is used to determine producers' optimum strategies, depending on their relative market power and overall production characteristics. Attention is then focused on the operation of single thermal power plants. Their short-term management plans and consequent effects on emission levels and residual life are described. The available reserve for primary and secondary control deriving from producers' market strategies is discussed. Some design options to improve combined cycles contribution to reserve service are finally described. The paper discusses these problems with a general approach, and uses many cases and examples derived from the current Italian scenario. (author)

  1. Power plant operation and management in a deregulated market

    International Nuclear Information System (INIS)

    Carraretto, Cristian

    2006-01-01

    This paper analyzes the influence of electricity deregulation on the design, operation and management of the power plants owned by strategic and non-strategic producers. After a sensitivity analysis aimed at finding market conditions of profitable operation for thermal and hydroelectric power plants, a Nash-equilibrium market model is used to determine producers' optimum strategies, depending on their relative market power and overall production characteristics. Attention is then focused on the operation of single thermal power plants. Their short-term management plans and consequent effects on emission levels and residual life are described. The available reserve for primary and secondary control deriving from producers' market strategies is discussed. Some design options to improve combined cycles contribution to reserve service are finally described. The paper discusses these problems with a general approach, and uses many cases and examples derived from the current Italian scenario. (author)

  2. Pricing and University Autonomy: Tuition Deregulation in Texas

    Directory of Open Access Journals (Sweden)

    Jeongeun Kim

    2016-04-01

    Full Text Available This paper investigates changes in tuition policies in the wake of tuition deregulation in Texas, which in 2003 transferred tuition-setting authority from the state legislature to institutions. We find that price increases accelerated, particularly at the most selective institutions. Institutions also began differentiating price by undergraduate program, raising relative prices for the most costly and lucrative majors, including engineering, business, nursing, and architecture. Price increases were particularly large for institutions with the highest initial costs and for programs with a high earnings premium within institutions, though lower for institutions with more low-income students. These distinctions suggest that public postsecondary institutions respond to microeconomic incentives when given greater autonomy to set price, and take some measures to alleviate impacts on low-income students. The Texas experience suggests that decentralized price-setting generates greater price differentiation within the public higher education system, both across and within institutions.

  3. Power quality and reliability issues in a deregulated energy market

    International Nuclear Information System (INIS)

    Huggins, M.J.

    1999-01-01

    The challenge of maintaining power quality and reliability in Ontario's new competitive electricity market was the focus of this paper. The intention of Ontario's deregulation is to lower costs and give customers more power and choice. However, some fear that costs pressures may lead to poorer quality. This paper reviewed the causes, costs, and responsibilities, and made some suggestions concerning how customers can protect their interests as the market opens. It was suggested that in order to assure power quality, especially during the transition period, customers need to take care to design their systems and equipment to tolerate some quality variations. Conversely, utilities need to strive for at least minimum industry standards under most conditions. Contracts should be carefully crafted, with responsibilities for reliability and quality clearly stated. 2 refs

  4. Impact of electricity market deregulation on information systems

    International Nuclear Information System (INIS)

    Pharabod, E.; Berrier, M.

    2005-01-01

    Electricity market deregulation is based on un-bundling of activities between generation, transmission and distribution. In a very short time, mechanisms were put in place in order to allow the new market participants to buy and sell electricity. The market operation requires to exchange information at various time horizon, from yearly to real time exchanges, between various actors geographically distributed. The recent market opening to professional customers has also increased the amount of data involved. The information system developed by RTE to manage these data is organised around referential data base, internal and external exchange tools. It must be operated respecting confidentiality of commercial data and being non discriminatory with actors. The security of this information system is now a key issue for the electricity market operation. (authors)

  5. Do cost-sharing and entry deregulation curb pharmaceutical innovation?

    Science.gov (United States)

    Grossmann, Volker

    2013-09-01

    This paper examines the role of both cost-sharing schemes in health insurance systems and the regulation of entry into the pharmaceutical sector for pharmaceutical R&D expenditure and drug prices. The analysis suggests that both an increase in the coinsurance rate and stricter price regulations adversely affect R&D spending in the pharmaceutical sector. In contrast, entry deregulation may lead to higher R&D spending of pharmaceutical companies. The relationship between R&D spending per firm and the number of firms may be hump-shaped. In this case, the number of rivals which maximizes R&D expenditure per firm is decreasing in the coinsurance rate and increasing in labor productivity. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Natural gas deregulation: have the handcuffs really been removed?

    International Nuclear Information System (INIS)

    Kelley, T.D.

    1995-01-01

    The natural gas market in New York State was reviewed and characterized as being very competitive. A brief description of the New York State Electric and Gas Corp. (NYSEG) was given. As regards recent developments, in October 1993, the New York Public Service Commission (NYPSC) instituted a proceeding (93-G-0932) on the restructuring of the gas market. Several guidelines for market restructuring were established as a result. The guidelines were in respect to service to consumers, safety of distribution, environmental implications, consumer concerns, gas rates, regulation, and access for core customers. The speaker noted that these guidelines did not promote deregulation. Competitive issues faced by local gas distributors were enumerated. Among these were (1)service to core and non-core customers (2)transition costs, (3)streaming, (4)unbundling and repackaged services, (5)price differentiation, and (6)small customer aggregation. It was expected that marketers would oppose the Public Service Commission giving local gas distributors additional pricing flexibility

  7. Electricity pricing and load dispatching in deregulated electricity market

    International Nuclear Information System (INIS)

    Geerli; Niioka, S.; Yokoyama, R.

    2003-01-01

    A rapid move to a market-based electric power industry will significantly alter the structure of electricity pricing and system operation. In this paper, we consider a game of negotiation in the electricity market, involving electric utilities, independent power producers (IPPs) and large-scale customers. We analyze the two-level game strategies for the negotiation process between utilities, IPPs and customers. These have been previously recognized as a way to come up with a rational decision for competitive markets, in which players intend to maximize their own profits. The derived operation rules based on competition can be viewed as an extension of the conventional equal incremental cost method for the deregulated power system. The proposed approach was applied to several systems to verify its effectiveness. (Author)

  8. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Charach, L.

    2002-01-01

    This paper provides a 15 month assessment of Alberta's new competitive electricity market. It also presents lessons that Ontario customers could learn from Alberta's experience. The goal for restructuring is to achieve lower electricity prices, competitive retail markets, increased flexibility of contracts, and to remove investment risks from consumers. Alberta's restructured market includes power generation, high voltage transmission, low voltage transmission and retail sales. Economists agree that deregulation has brought lower prices and other consumer benefits despite some imperfections. After one year, prices in Alberta have gone down from $130/MWh to $30/MWh. Power supply has increased along with demand response, market competitiveness, liquidity, and thermal and economic efficiency. In 2001, Alberta was a net exporter of electricity. In 2001, it was ranked by the Center for Advancement of Energy Markets (CAEM) which ranks states and provinces by 22 attributes for how they are restructuring their power markets. Alberta ranked first overall in North America. Ontario ranked sixteenth. 4 tabs., 5 figs

  9. Steady state security assessment in deregulated power systems

    Science.gov (United States)

    Manjure, Durgesh Padmakar

    Power system operations are undergoing changes, brought about primarily due to deregulation and subsequent restructuring of the power industry. The primary intention of the introduction of deregulation in power systems was to bring about competition and improved customer focus. The underlying motive was increased economic benefit. Present day power system analysis is much different than what it was earlier, essentially due to the transformation of the power industry from being cost-based to one that is price-based and due to open access of transmission networks to the various market participants. Power is now treated as a commodity and is traded in an open market. The resultant interdependence of the technical criteria and the economic considerations has only accentuated the need for accurate analysis in power systems. The main impetus in security analysis studies is on efficient assessment of the post-contingency status of the system, accuracy being of secondary consideration. In most cases, given the time frame involved, it is not feasible to run a complete AC load flow for determining the post-contingency state of the system. Quite often, it is not warranted as well, as an indication of the state of the system is desired rather than the exact quantification of the various state variables. With the inception of deregulation, transmission networks are subjected to a host of multilateral transactions, which would influence physical system quantities like real power flows, security margins and voltage levels. For efficient asset utilization and maximization of the revenue, more often than not, transmission networks are operated under stressed conditions, close to security limits. Therefore, a quantitative assessment of the extent to which each transaction adversely affects the transmission network is required. This needs to be done accurately as the feasibility of the power transactions and subsequent decisions (execution, curtailment, pricing) would depend upon the

  10. Microtubule reorganization in tobacco BY-2 cells stably expressing GFP-MBD

    Science.gov (United States)

    Granger, C. L.; Cyr, R. J.

    2000-01-01

    Microtubule organization plays an important role in plant morphogenesis; however, little is known about how microtubule arrays transit from one organized state to another. The use of a genetically incorporated fluorescent marker would allow long-term observation of microtubule behavior in living cells. Here, we have characterized a Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line that had been stably transformed with a gfp-mbd construct previously demonstrated to label microtubules (J. Marc et al., 1998, Plant Cell 10: 1927-1939). Fluorescence levels were low, but interphase and mitotic microtubule arrays, as well as the transitions between these arrays, could be observed in individual gfp-mbd-transformed cells. By comparing several attributes of transformed and untransformed cells it was concluded that the transgenic cells are not adversely affected by low-level expression of the transgene and that these cells will serve as a useful and accurate model system for observing microtubule reorganization in vivo. Indeed, some initial observations were made that are consistent with the involvement of motor proteins in the transition between the spindle and phragmoplast arrays. Our observations also support the role of the perinuclear region in nucleating microtubules at the end of cell division with a progressive shift of these microtubules and/or nucleating activity to the cortex to form the interphase cortical array.

  11. Feeding cells induced by phytoparasitic nematodes require γ-tubulin ring complex for microtubule reorganization.

    Directory of Open Access Journals (Sweden)

    Mohamed Youssef Banora

    2011-12-01

    Full Text Available Reorganization of the microtubule network is important for the fast isodiametric expansion of giant-feeding cells induced by root-knot nematodes. The efficiency of microtubule reorganization depends on the nucleation of new microtubules, their elongation rate and activity of microtubule severing factors. New microtubules in plants are nucleated by cytoplasmic or microtubule-bound γ-tubulin ring complexes. Here we investigate the requirement of γ-tubulin complexes for giant feeding cells development using the interaction between Arabidopsis and Meloidogyne spp. as a model system. Immunocytochemical analyses demonstrate that γ-tubulin localizes to both cortical cytoplasm and mitotic microtubule arrays of the giant cells where it can associate with microtubules. The transcripts of two Arabidopsis γ-tubulin (TUBG1 and TUBG2 and two γ-tubulin complex proteins genes (GCP3 and GCP4 are upregulated in galls. Electron microscopy demonstrates association of GCP3 and γ-tubulin as part of a complex in the cytoplasm of giant cells. Knockout of either or both γ-tubulin genes results in the gene dose-dependent alteration of the morphology of feeding site and failure of nematode life cycle completion. We conclude that the γ-tubulin complex is essential for the control of microtubular network remodelling in the course of initiation and development of giant-feeding cells, and for the successful reproduction of nematodes in their plant hosts.

  12. A structural model for microtubule minus-end recognition and protection by CAMSAP proteins

    NARCIS (Netherlands)

    Atherton, Joseph; Jiang, Kai; Stangier, Marcel M.; Luo, Yanzhang; Hua, Shasha; Houben, Klaartje; Van Hooff, Jolien J.E.; Joseph, Agnel Praveen; Scarabelli, Guido; Grant, Barry J.; Roberts, Anthony J.; Topf, Maya; Steinmetz, Michel O.; Baldus, Marc; Moores, Carolyn A.; Akhmanova, Anna

    2017-01-01

    CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among

  13. BDI position on energy policy and energy market deregulation

    International Nuclear Information System (INIS)

    Kreklau, C.

    2003-01-01

    Secure energy supplies are indispensable for our modern way of life and our economy. Energy policy is a part of economic policy and must be shaped within the magic triangle of objectives, i.e. security, competitiveness, environmental compatibility. As a result of their outstanding role, electricity and natural gas, with respective shares of 70% in industrial energy use and 85% in energy costs, are in the focus of energy policy interest of the Federation of German Industries (BDI). One important development over the past few years has been the deregulation of the markets for electricity and gas. However, the markedly lower electricity rates to be paid by industry, commercial tariff consumers, and private customers are being offset by new burdens arising from government intervention and taxes. Other dirigistic interventions into the energy market by the red-green federal government since 1998, referred to as 'turning point of energy policy', are invalidating what market opening had been achieved. With a view to a sustainable energy policy for the future, BDI pleads in favor of a broad energy mix. In a mix neutral with respect to competition, this includes the classical energy sources, the renewables, and low-cost, environmentally friendly nuclear power. In principle, it is the forces of the market, coupled with responsible action, which are to steer further developments. On a European level, speedy implementation of the opening of the electricity and gas markets, as decided, should be urged. It is important that the leeway won as a result of deregulation not be constrained again by new regulations. More market, less regulation, and more direct responsibility must provide room for a powerful energy supply system under the premises of the triangle of objectives referred to above. (orig.) [de

  14. Public understanding of environmental impacts of electricity deregulation

    International Nuclear Information System (INIS)

    Johnson, Branden B.; Frank, Pamela G.

    2006-01-01

    Electricity deregulation has aroused concern that environmental quality might be harmed by consumer preferences for cheap, 'dirty' (e.g., coal) electricity products, despite the perhaps stronger influence of supply side policy on environmental impacts. This outcome depends on public understanding of the environmental impacts of their decisions, which this study explored with interviews, focus groups, and surveys in New Jersey. People had thought little about the topic, were unable to articulate how electricity production might affect the environment except in very general terms, and were mostly unwilling to guess whether deregulation's impacts would be negative, neutral or positive. Those who did guess expected negative impacts less than any other kind. Reactions to specific 'reasons' for expecting no, positive or negative impacts suggested that consumers had little structure to their mental models in this area; for example, people who thought positive-impact reasons were probably true were not necessarily likely to see negative-impact reasons as probably false. However, in the aggregate, people seemed to have a fairly consistent ranking of energy sources by expected negative environmental impacts. Earlier research found that consumers comparing two electricity products on environmental impacts reached different decisions if they had energy-source-only or energy-source-plus-emissions information. Although regulator-required 'environmental labels' for electricity products provide both source and emissions data, it is not clear that they do an adequate job of both alerting consumers to the possibility of negative environmental impacts and identifying the relative life-cycle impacts of different products so as to produce informed consumer decisions

  15. The economics of energy storage in 14 deregulated power markets

    International Nuclear Information System (INIS)

    Figueiredo, F.C.; Flynn, P.C.; Cabral, E.A.

    2006-01-01

    In regulated power markets, electricity is stored to better utilize existing generation and to defer costly investment in generation. The justification is a reduction in the overall regulated price of power compared to the alternative investment in new primary generation. However, any storage of electrical power also involves a capital investment and incurs the cost of inefficiency. In deregulated energy markets, the sale of electricity or ancillary services from pumped storage can be evaluated based on each individual project. The economic basis for power storage is that power is purchased during periods of low price and resold during periods of high price. This study used historical power price data from 14 deregulated markets around the world to evaluate the economic incentive to use pumped storage for electrical energy. Each market was shown to have a unique average diurnal power price profile that results in a unique price spread for pumped storage. The diurnal price pattern and efficiency of storage was used to assess the net income potential from energy sales from pumped storage for each market. The markets were ranked in terms of the incentive to invest in pumped energy storage as well as on available revenue, and on potential return on investment. An optimal operating profile was illustrated in detail based on historical price patterns for one of the markets. The net income potential was then combined with the capital and operating cost of pumped storage. The adequacy of return on investment for pumped storage was analyzed by two different methods. The differences between markets stem from different diurnal power price patterns that reflect the generation mix, market design and participant behaviours. 17 refs., 7 tabs., 7 figs., 1 appendix

  16. Investments into plant replacements in a deregulated electricity market

    International Nuclear Information System (INIS)

    Elsaesser, R.F.

    2004-01-01

    The amendment to the Power Energy Act in April 1998 marked the complete deregulation of the electricity market in Germany. The debate is now beginning about ways and means to ensure new capital investments safeguarding the continuity of supply. The present power plant park has been characterized by a broad mix of primary energy sources and, admittedly, by some overcapacity as well. However, any further reduction of generating capacity will be at the expense of the continuity of supply. Although electricity prices in Germany are on the rise again after a clear drop, they have not yet reached a level sufficient for new investments. Only subsidized power plants are recovering their full costs. The question is for how long our economy is going to sustain this state of affairs. The balance among the energy policy goals of continuity of supply, environmental performance, and economic efficiency has been upset. In the period up until 2020, Germany alone will require approx. 37,000 MW of new generating capacity. Renewable and decentralized technologies alone do not constitute a sufficient and reliable alternative. However, there is the matter also of the practical feasibility of building the new power plants required. No experience is as yet available with re-investment cycles in the deregulated electricity market. Options are needed for a diversified structure of primary energy sources. There must be neither political definition of generating technologies nor exaggerated goals of environmental protection and climate protection. We advocate the free system of market prices and free access to the market. Major players able to guarantee sufficient security of investments are needed to cope with the challenges ahead. New investments with a life of thirty to forty years require a modicum of stability and realism in political framework conditions. (orig.)

  17. Economic use of a nuclear park in a deregulated market

    International Nuclear Information System (INIS)

    Eliasson, L.

    2000-01-01

    The deregulation of the electricity market has created a new situation for plant life management. In order to be competitive it is important to cut costs. All means to cut costs have to be used while still maintaining safety and production capacity. The possibilities to invest in modernization are limited to the absolute necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long strategic planning. New safety requirements from the regulatory body have to be discussed between the industry and the regulator. The cost of new requirements must be compared to the benefit for the safety. The regulator is today requested to carry out such analyses and do so in most cases. Still the electricity market is international and the requirements of the regulator must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public and political understanding and acceptance. Especially in Sweden a lot of effort is spent on trying to get harmonized taxes and environmental fees. Nuclear power is paying for all its costs and the external costs are already internalized. Still, at the deregulated market, nuclear power is competitive, creating positive cash flow, a good object for investments and environmentally favourable. Threats have to be removed to get prerequisites for long term strategic planning and investments. Steps in that direction will be increasing electricity demand, in the near future, which will make the prices to raise creating an improved economic situation. Also the very serious worries about climate change will strengthen the competitiveness of nuclear power. (author)

  18. Kindlin1 regulates microtubule function to ensure normal mitosis.

    Science.gov (United States)

    Patel, Hitesh; Stavrou, Ifigeneia; Shrestha, Roshan L; Draviam, Viji; Frame, Margaret C; Brunton, Valerie G

    2016-08-01

    Loss of Kindlin 1 (Kin1) results in the skin blistering disorder Kindler Syndrome (KS), whose symptoms also include skin atrophy and reduced keratinocyte proliferation. Kin1 binds to integrins to modulate their activation and more recently it has been shown to regulate mitotic spindles and cell survival in a Plk1-dependent manner. Here we report that short-term Kin1 deletion in mouse skin results in impaired mitosis, which is associated with reduced acetylated tubulin (ac-tub) levels and cell proliferation. In cells, impaired mitosis and reduced ac-tub levels are also accompanied by reduced microtubule stability, all of which are rescued by HDAC6 inhibition. The ability of Kin1 to regulate HDAC6-dependent cellular ac-tub levels is dependent on its phosphorylation by Plk1. Taken together, these data define a novel role for Kin1 in microtubule acetylation and stability and offer a mechanistic insight into how certain KS phenotypes, such as skin atrophy and reduced cell proliferation, arise. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  19. Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

    International Nuclear Information System (INIS)

    Crawford, J.M.; Gollan, J.L.

    1988-01-01

    Modulation of bile pigment excretion by bile salts has been attributed to modification of canalicular membrane transport or a physical interaction in bile. Based on the observation that a microtubule-dependent pathway is involved in the hepatocellular transport of bile salts, the authors investigated the possibility that bilirubin glucuronides are associated with bile salts during intracellular transport. Experiments were conducted in intact rats (basal) or after overnight biliary diversion and intravenous reinfusion of taurocholate (depleted/reinfused). All rats were pretreated with intravenous low-dose colchicine or its inactive isomer lumicolchicine. Biliary excretion of radiolabeled bilirubin glucuronides derived from tracer [ 14 C]bilirubin-[ 3 H]bilirubin monoglucuronide (coinjected iv) was unchanged in basal rats but was consistently delayed in depleted/reinfused rats. This was accompanied by a significant shift toward bilirubin diglucuronide formation from both substrates. In basal Gunn rats, with deficient bilirubin glucuronidation, biliary excretion of intravenous [ 14 C]bilirubin monoglucuronide-[ 3 H]bilirubin diglucuronide was unaffected by colchicine but was retarded in depleted/reinfused Gunn rats. Colchicine had no effect on the rate of bilirubin glucuronidation in vitro in rat liver microsomes. They conclude that a portion of the bilirubin glucuronides generated endogenously in hepatocytes or taken up directly from plasma may be cotransported with bile salts to the bile canalicular membrane via a microtubule-dependent mechanism

  20. Endoplasmic-reticulum-mediated microtubule alignment governs cytoplasmic streaming.

    Science.gov (United States)

    Kimura, Kenji; Mamane, Alexandre; Sasaki, Tohru; Sato, Kohta; Takagi, Jun; Niwayama, Ritsuya; Hufnagel, Lars; Shimamoto, Yuta; Joanny, Jean-François; Uchida, Seiichi; Kimura, Akatsuki

    2017-04-01

    Cytoplasmic streaming refers to a collective movement of cytoplasm observed in many cell types. The mechanism of meiotic cytoplasmic streaming (MeiCS) in Caenorhabditis elegans zygotes is puzzling as the direction of the flow is not predefined by cell polarity and occasionally reverses. Here, we demonstrate that the endoplasmic reticulum (ER) network structure is required for the collective flow. Using a combination of RNAi, microscopy and image processing of C. elegans zygotes, we devise a theoretical model, which reproduces and predicts the emergence and reversal of the flow. We propose a positive-feedback mechanism, where a local flow generated along a microtubule is transmitted to neighbouring regions through the ER. This, in turn, aligns microtubules over a broader area to self-organize the collective flow. The proposed model could be applicable to various cytoplasmic streaming phenomena in the absence of predefined polarity. The increased mobility of cortical granules by MeiCS correlates with the efficient exocytosis of the granules to protect the zygotes from osmotic and mechanical stresses.

  1. Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

    Science.gov (United States)

    Okada, Naoyuki; Sato, Masamitsu

    2015-01-01

    Spindle microtubules capture and segregate chromosomes and, therefore, their assembly is an essential event in mitosis. To carry out their mission, many key players for microtubule formation need to be strictly orchestrated. Particularly, proteins that assemble the spindle need to be translocated at appropriate sites during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran, controls this translocation. Ran plays many roles in many cellular events: nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic spindle, and reorganization of the nuclear envelope at the mitotic exit. Although these events are seemingly distinct, recent studies demonstrate that the mechanisms underlying these phenomena are substantially the same as explained by molecular interplay of the master regulator Ran, the transport factor importin, and its cargo proteins. Our review focuses on how the transport machinery regulates mitotic progression of cells. We summarize translocation mechanisms governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP targets in fission yeast that promote spindle formation. We also discuss the coordination of the spatial and temporal regulation of proteins from the viewpoint of transport machinery. We propose that the transport machinery is an essential key that couples the spatial and temporal events in cells. PMID:26308057

  2. Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells

    Science.gov (United States)

    Wang, Jennifer T; Kong, Dong; Hoerner, Christian R; Loncarek, Jadranka

    2017-01-01

    Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next. PMID:28906251

  3. Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells.

    Science.gov (United States)

    Wang, Jennifer T; Kong, Dong; Hoerner, Christian R; Loncarek, Jadranka; Stearns, Tim

    2017-09-14

    Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next.

  4. Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.

    Science.gov (United States)

    Revenu, Céline; Streichan, Sebastian; Donà, Erika; Lecaudey, Virginie; Hufnagel, Lars; Gilmour, Darren

    2014-03-01

    The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.

  5. Overview of the developments in the domestic airline industry in South Africa since market deregulation

    Directory of Open Access Journals (Sweden)

    Rose Luke

    2013-11-01

    Full Text Available Deregulation or liberalisation of air transport has had major global impacts on the domestic air transport markets, with effects ranging from stimulation to changes in the structure and functioning of these markets. In South Africa, deregulation has had wide-reaching effects on the domestic market. The purpose of this article was to investigate the current domestic air transport market. A literature review was performed to examine the effects of deregulation in other domestic air transport markets around the world. This was followed by a review of the South African domestic air transport market prior to deregulation in order to determine the changes that were made following deregulation. The ten-year period immediately following deregulation was also examined; this period was characterised by relatively large numbers of market entries and exits. A database was obtained from the Airports Company South Africa; air traffic movements, passenger numbers and load factors were evaluated. The study showed that the market is still characterised by regular market entries and exits. Also that the entry of the low-cost carriers has stimulated the market, resulting in increased air traffic movements, higher passenger numbers, higher load factors in general and the opening of a secondary airport in Gauteng, Lanseria International. Deregulation and, more specifically, the entry of the low-cost carriers has resulted in structural changes in the market and more choice for passengers.

  6. Collective behavior of minus-ended motors in mitotic microtubule asters gliding toward DNA

    International Nuclear Information System (INIS)

    Athale, Chaitanya A; Dinarina, Ana; Nedelec, Francois; Karsenti, Eric

    2014-01-01

    Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions. (paper)

  7. Internet-based wide area measurement applications in deregulated power systems

    Science.gov (United States)

    Khatib, Abdel-Rahman Amin

    Since the deregulation of power systems was started in 1989 in the UK, many countries have been motivated to undergo deregulation. The United State started deregulation in the energy sector in California back in 1996. Since that time many other states have also started the deregulation procedures in different utilities. Most of the deregulation market in the United States now is in the wholesale market area, however, the retail market is still undergoing changes. Deregulation has many impacts on power system network operation and control. The number of power transactions among the utilities has increased and many Independent Power Producers (IPPs) now have a rich market for competition especially in the green power market. The Federal Energy Regulatory Commission (FERC) called upon utilities to develop the Regional Transmission Organization (RTO). The RTO is a step toward the national transmission grid. RTO is an independent entity that will operate the transmission system in a large region. The main goal of forming RTOs is to increase the operation efficiency of the power network under the impact of the deregulated market. The objective of this work is to study Internet based Wide Area Information Sharing (WAIS) applications in the deregulated power system. The study is the first step toward building a national transmission grid picture using information sharing among utilities. Two main topics are covered as applications for the WAIS in the deregulated power system, state estimation and Total Transfer Capability (TTC) calculations. As a first step for building this national transmission grid picture, WAIS and the level of information sharing of the state estimation calculations have been discussed. WAIS impacts to the TTC calculations are also covered. A new technique to update the TTC using on line measurements based on WAIS created by sharing state estimation is presented.

  8. A hybrid DE–PS algorithm for load frequency control under deregulated power system with UPFC and RFB

    Directory of Open Access Journals (Sweden)

    Rabindra Kumar Sahu

    2015-09-01

    Full Text Available In this paper, a Modified Integral Derivative (MID controller is proposed for Load Frequency Control (LFC of multi-area multi-source power system in deregulated environment. The multi-source power system is having different sources of power generation such as thermal, hydro, wind and diesel generating units considering boiler dynamics for thermal plants, Generation Rate Constraint (GRC and Governor Dead Band (GDB non-linearity. The superiority of proposed hybrid Differential Evolution and Pattern Search (hDE-PS optimized MID controller over GA and DE techniques is demonstrated. Further, the effectiveness of proposed hDE-PS optimized MID controller over Integral (I and Integral Derivative (ID controller is verified. Then, to further improve the system performance, Unified Power Flow Controller (UPFC is placed in the tie-line and Redox Flow Batteries (RFBs are considered in the first area. The performance of proposed approach is evaluated at all possible power transactions that take place in a deregulated power market.

  9. Modelling the transition from cost-based to bid-based pricing in a deregulated electricity-market

    Energy Technology Data Exchange (ETDEWEB)

    Druce, Donald J. [BC Hydro, 6911 Southpoint Drive, Burnaby, British Columbia (Canada)

    2007-12-15

    Alberta is a province in western Canada with a deregulated electricity-market. Market clearing prices for most hours reflect the cost of either coal-fired or gas-fired thermal generation. Whenever there is a chronic shortage of generation or even a temporary one due to an outage, prices can be bid much higher than fuel costs would suggest. The province of British Columbia borders Alberta to the west and its electric utility, BC Hydro, has a history of trade with the utilities in Alberta. BC Hydro has predominantly hydroelectric resources and large storage reservoirs. Prior to Alberta's deregulation in 1996, BC Hydro was able to enter into mutually beneficial load-factoring contracts with the Alberta utilities. Now, as long as the transmission is available, BC Hydro can buy low priced off-peak coal-fired energy and sell into the high priced periods without having to share the benefits. BC Hydro uses a combination of econometric and Monte Carlo modelling to simulate hourly price-duration curves for Alberta that capture both cost-based and bid-based characteristics. This approach provides a good fit with the stochastic dynamic programming model that BC Hydro has developed for its mid-term hydro scheduling. (author)

  10. Modelling the transition from cost-based to bid-based pricing in a deregulated electricity-market

    International Nuclear Information System (INIS)

    Druce, Donald J.

    2007-01-01

    Alberta is a province in western Canada with a deregulated electricity-market. Market clearing prices for most hours reflect the cost of either coal-fired or gas-fired thermal generation. Whenever there is a chronic shortage of generation or even a temporary one due to an outage, prices can be bid much higher than fuel costs would suggest. The province of British Columbia borders Alberta to the west and its electric utility, BC Hydro, has a history of trade with the utilities in Alberta. BC Hydro has predominantly hydroelectric resources and large storage reservoirs. Prior to Alberta's deregulation in 1996, BC Hydro was able to enter into mutually beneficial load-factoring contracts with the Alberta utilities. Now, as long as the transmission is available, BC Hydro can buy low priced off-peak coal-fired energy and sell into the high priced periods without having to share the benefits. BC Hydro uses a combination of econometric and Monte Carlo modelling to simulate hourly price-duration curves for Alberta that capture both cost-based and bid-based characteristics. This approach provides a good fit with the stochastic dynamic programming model that BC Hydro has developed for its mid-term hydro scheduling

  11. Decision modelling tools for utilities in the deregulated energy market

    Energy Technology Data Exchange (ETDEWEB)

    Makkonen, S. [Process Vision Oy, Helsinki (Finland)

    2005-07-01

    This thesis examines the impact of the deregulation of the energy market on decision making and optimisation in utilities and demonstrates how decision support applications can solve specific encountered tasks in this context. The themes of the thesis are presented in different frameworks in order to clarify the complex decision making and optimisation environment where new sources of uncertainties arise due to the convergence of energy markets, globalisation of energy business and increasing competition. This thesis reflects the changes in the decision making and planning environment of European energy companies during the period from 1995 to 2004. It also follows the development of computational performance and evolution of energy information systems during the same period. Specifically, this thesis consists of studies at several levels of the decision making hierarchy ranging from top-level strategic decision problems to specific optimisation algorithms. On the other hand, the studies also follow the progress of the liberalised energy market from the monopolistic era to the fully competitive market with new trading instruments and issues like emissions trading. This thesis suggests that there is an increasing need for optimisation and multiple criteria decision making methods, and that new approaches based on the use of operations research are welcome as the deregulation proceeds and uncertainties increase. Technically, the optimisation applications presented are based on Lagrangian relaxation techniques and the dedicated Power Simplex algorithm supplemented with stochastic scenario analysis for decision support, a heuristic method to allocate common benefits and potential losses of coalitions of power companies, and an advanced Branch- and-Bound algorithm to solve efficiently nonconvex optimisation problems. The optimisation problems are part of the operational and tactical decision making process that has become very complex in the recent years. Similarly

  12. Brassinosteroids regulate pavement cell growth by mediating BIN2-induced microtubule stabilization.

    Science.gov (United States)

    Liu, Xiaolei; Yang, Qin; Wang, Yuan; Wang, Linhai; Fu, Ying; Wang, Xuelu

    2018-02-23

    Brassinosteroids (BRs), a group of plant steroid hormones, play important roles in regulating plant development. The cytoskeleton also affects key developmental processes and a deficiency in BR biosynthesis or signaling leads to abnormal phenotypes similar to those of microtubule-defective mutants. However, how BRs regulate microtubule and cell morphology remains unknown. Here, using liquid chromatography-tandem mass spectrometry, we identified tubulin proteins that interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative regulator of BR responses in plants. In vitro and in vivo pull-down assays confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical microtubules were more sensitive to treatment with the microtubule-disrupting drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2-1, cortical microtubules were insensitive to oryzalin treatment. These results provide important insight into how BR regulates plant pavement cell and leaf growth by mediating the stabilization of microtubules by BIN2.

  13. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria.

    Directory of Open Access Journals (Sweden)

    Carsten Schwan

    2009-10-01

    Full Text Available Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by production of the Rho GTPase-glucosylating toxins A and B. Recently emerging hypervirulent Clostridium difficile strains additionally produce the binary ADP-ribosyltransferase toxin CDT (Clostridium difficile transferase, which ADP-ribosylates actin and inhibits actin polymerization. Thus far, the role of CDT as a virulence factor is not understood. Here we report by using time-lapse- and immunofluorescence microscopy that CDT and other binary actin-ADP-ribosylating toxins, including Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin, induce redistribution of microtubules and formation of long (up to >150 microm microtubule-based protrusions at the surface of intestinal epithelial cells. The toxins increase the length of decoration of microtubule plus-ends by EB1/3, CLIP-170 and CLIP-115 proteins and cause redistribution of the capture proteins CLASP2 and ACF7 from microtubules at the cell cortex into the cell interior. The CDT-induced microtubule protrusions form a dense meshwork at the cell surface, which wrap and embed bacterial cells, thereby largely increasing the adherence of Clostridia. The study describes a novel type of microtubule structure caused by less efficient microtubule capture and offers a new perspective for the pathogenetic role of CDT and other binary actin-ADP-ribosylating toxins in host-pathogen interactions.

  14. Buckling analysis of orthotropic protein microtubules under axial and radial compression based on couple stress theory.

    Science.gov (United States)

    Beni, Yaghoub Tadi; Zeverdejani, M Karimi; Mehralian, Fahimeh

    2017-10-01

    Protein microtubules (MTs) are one of the important intercellular components and have a vital role in the stability and strength of the cells. Due to applied external loads, protein microtubules may be involved buckling phenomenon. Due to impact of protein microtubules in cell reactions, it is important to determine their critical buckling load. Considering nature of protein microtubules, various parameters are effective on microtubules buckling. The small size of microtubules and also lack of uniformity of MTs properties in different directions caused the necessity of accuracy in the analysis of these bio-structure. In fact, microtubules must be considered as a size dependent cylinder, which behave as an orthotropic material. Hence, in the present work using first-order shear deformation model (FSDT), the buckling equations of anisotropic MTs are derived based on new modified couple stress theory (NMCST). After solving the stability equations, the influences of various parameters are measured on the MTs critical buckling load. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Measurement of in vitro microtubule polymerization by turbidity and fluorescence.

    Science.gov (United States)

    Mirigian, Matthew; Mukherjee, Kamalika; Bane, Susan L; Sackett, Dan L

    2013-01-01

    Tubulin polymerization may be conveniently monitored by the increase in turbidity (optical density, or OD) or by the increase in fluorescence intensity of diamidino-phenylindole. The resulting data can be a quantitative measure of microtubule (MT) assembly, but some care is needed in interpretation, especially of OD data. Buffer formulations used for the assembly reaction significantly influence the polymerization, both by altering the critical concentration for polymerization and by altering the exact polymer produced-for example, by increasing the production of sheet polymers in addition to MT. Both the turbidity and the fluorescence methods are useful for demonstrating the effect of MT-stabilizing or -destabilizing additives. 2013 Published by Elsevier Inc.

  16. HSPB1 facilitates the formation of non-centrosomal microtubules.

    Directory of Open Access Journals (Sweden)

    Leonardo Almeida-Souza

    Full Text Available The remodeling capacity of microtubules (MT is essential for their proper function. In mammals, MTs are predominantly formed at the centrosome, but can also originate from non-centrosomal sites, a process that is still poorly understood. We here show that the small heat shock protein HSPB1 plays a role in the control of non-centrosomal MT formation. The HSPB1 expression level regulates the balance between centrosomal and non-centrosomal MTs. The HSPB1 protein can be detected specifically at sites of de novo forming non-centrosomal MTs, while it is absent from the centrosomes. In addition, we show that HSPB1 binds preferentially to the lattice of newly formed MTs in vitro, suggesting that its function occurs by stabilizing MT seeds. Our findings open new avenues for the understanding of the role of HSPB1 in the development, maintenance and protection of cells with specialized non-centrosomal MT arrays.

  17. Near-atomic model of microtubule-tau interactions.

    Science.gov (United States)

    Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon; Downing, Kenneth H; DiMaio, Frank; Nogales, Eva

    2018-06-15

    Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  18. STIM1-Directed Reorganization of Microtubules in Activated Mast Cells

    Czech Academy of Sciences Publication Activity Database

    Hájková, Zuzana; Bugajev, Viktor; Dráberová, Eduarda; Vinopal, Stanislav; Dráberová, Lubica; Janáček, Jiří; Dráber, Petr; Dráber, Pavel

    2011-01-01

    Roč. 186, č. 2 (2011), s. 913-923 ISSN 0022-1767 R&D Projects: GA ČR(CZ) GD204/09/H084; GA ČR GA204/09/1777; GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA MŠk LC545; GA MŠk(CZ) LC06063; GA AV ČR KAN200520701 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50110509 Keywords : STIM1 * bone marrow-derived mast cells * microtubules Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.788, year: 2011

  19. A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows.

    Science.gov (United States)

    Monteith, Corey E; Brunner, Matthew E; Djagaeva, Inna; Bielecki, Anthony M; Deutsch, Joshua M; Saxton, William M

    2016-05-10

    The transport of cytoplasmic components can be profoundly affected by hydrodynamics. Cytoplasmic streaming in Drosophila oocytes offers a striking example. Forces on fluid from kinesin-1 are initially directed by a disordered meshwork of microtubules, generating minor slow cytoplasmic flows. Subsequently, to mix incoming nurse cell cytoplasm with ooplasm, a subcortical layer of microtubules forms parallel arrays that support long-range, fast flows. To analyze the streaming mechanism, we combined observations of microtubule and organelle motions with detailed mathematical modeling. In the fast state, microtubules tethered to the cortex form a thin subcortical layer and undergo correlated sinusoidal bending. Organelles moving in flows along the arrays show velocities that are slow near the cortex and fast on the inward side of the subcortical microtubule layer. Starting with fundamental physical principles suggested by qualitative hypotheses, and with published values for microtubule stiffness, kinesin velocity, and cytoplasmic viscosity, we developed a quantitative coupled hydrodynamic model for streaming. The fully detailed mathematical model and its simulations identify key variables that can shift the system between disordered (slow) and ordered (fast) states. Measurements of array curvature, wave period, and the effects of diminished kinesin velocity on flow rates, as well as prior observations on f-actin perturbation, support the model. This establishes a concrete mechanistic framework for the ooplasmic streaming process. The self-organizing fast phase is a result of viscous drag on kinesin-driven cargoes that mediates equal and opposite forces on cytoplasmic fluid and on microtubules whose minus ends are tethered to the cortex. Fluid moves toward plus ends and microtubules are forced backward toward their minus ends, resulting in buckling. Under certain conditions, the buckling microtubules self-organize into parallel bending arrays, guiding varying directions

  20. MTB-3, a microtubule plus-end tracking protein (+TIP of Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Rosa R Mouriño-Pérez

    Full Text Available The microtubule (MT "plus end" constitutes the platform for the accumulation of a structurally and functionally diverse group of proteins, collectively called "MT plus-end tracking proteins" (+TIPs. +TIPs control MT dynamics and link MTs to diverse sub-cellular structures. Neurospora crassaMicroTubule Binding protein-3 (MTB-3 is the homolog of yeast EB1, a highly conserved +TIP. To address the function of MTB-3, we examined strains with mtb-3 deletions, and we tagged MTB-3 with GFP to assess its dynamic behavior. MTB-3-GFP was present as comet-like structures distributed more or less homogeneously within the hyphal cytoplasm, and moving mainly towards the apex at speeds up to 4× faster than the normal hyphal elongation rates. MTB-3-GFP comets were present in all developmental stages, but were most abundant in mature hyphae. MTB-3-GFP comets were observed moving in anterograde and retrograde direction along the hypha. Retrograde movement was also observed as originating from the apical dome. The integrity of the microtubular cytoskeleton affects the presence and dynamics of MTB-3-GFP comets, while actin does not seem to play a role. The size of MTB-3-GFP comets is affected by the absence of dynactin and conventional kinesin. We detected no obvious morphological phenotypes in Δmtb-3 mutants but there were fewer MTs in Δmtb-3, MTs were less bundled and less organized. Compared to WT, both MT polymerization and depolymerization rates were significantly decreased in Δmtb-3. In summary, the lack of MTB-3 affects overall growth and morphological phenotypes of N. crassa only slightly, but deletion of mtb-3 has strong effect on MT dynamics.

  1. A robust mixed H2/H∞ based LFC of a deregulated power system including SMES

    International Nuclear Information System (INIS)

    Shayeghi, H.; Jalili, A.; Shayanfar, H.A.

    2008-01-01

    This paper presents a new robust decentralized controller based on mixed H 2 /H ∞ control technique for the solution of load frequency control (LFC) problem including superconducting magnetic energy storage (SMES) in a deregulated electricity environment. To achieve decentralization, in each control area, the connections between this area and the rest of the system and the effects of possible contracts are treated as a set of new disturbance signals. In order to minimize effects of load disturbances and to achieve desired level of robust performance in the presence of modeling uncertainties and practical constraints on control action the idea of mixed H 2 /H ∞ control technique is being used for the solution of LFC problem. This newly developed design strategy combines advantage of H 2 and H ∞ control syntheses and gives a powerful multi-objectives design addressed by the linear matrix inequalities (LMI) technique. To demonstrate the effectiveness of the proposed method a four-area restructured power system is considered as a test system under different operating conditions. The simulation results with the proposed controller are shown to maintain robust performance in the presence of SMES unit in two areas at power system and without SMES unit in any of the areas. Analysis reveals that the proposed control strategy with considering SMES unit improves significantly the dynamical performances of system such as settling time and overshoot against parametric uncertainties for a wide range of area load demands and disturbances in either of the areas even in the presence of system nonlinearities

  2. Stochastic control for risk under deregulated electricity market : a case study using a new formulation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.L.; Ponnambalam, K. [Waterloo Univ., ON (Canada). Dept. of Systems Design Engineering

    2005-08-01

    A study was conducted to address some of the multi-reservoir operational problems associated with hydropower generation. Inflow, release, spill and storage are some of the large scale, nonlinear and stochastic problems that can be solved using the Fletcher Ponnambalam (FP) model for risk management in hydropower systems under deregulated energy markets. The main objective is to maximize benefits and minimize the total cost while satisfying the system constraints. The FP model was developed for the first and second order of storage state distributions in terms of inflow distribution. The FP method is suitable for multi-reservoir problems because it offers statistical information on the nature of random behaviour of the system state variables without discretization. It is a cost-effective method because it avoids a scenario-based optimization. In this study, price uncertainty was introduced into the model along with inflow uncertainty. The FP model and the Bender's Decomposition method were applied to the Lake Nipigon reservoir system. The FP results were compared with the stochastic dual dynamic programming. Results show that the FP method achieves optimum operations, including risk minimization. However, sensitivity analysis must always be carried out because the FP model is sensitive to initial values. 10 refs., 1 tab., 8 figs., 1 appendix.

  3. Deregulation and competitive power markets -- Its impact on developing economies

    International Nuclear Information System (INIS)

    Saran, K.

    1998-01-01

    The aim of privatization in developed countries is to encourage competition in generation and supply of power whereas the focus of developing economies is to bridge the demand supply gap by addition of capacity. However, there needs to be a reconciliation between these two apparently having conflicting objectives even in case of developing economies. In competitive power markets it is necessary that rules of the game are identified in advance and followed uniformly by all players. Existence of a ''referee'' would be necessary to regulate the game so as to ensure fair play. The regulatory institution would serve this purpose and work as a stimulator to development of privatization and competitive power markets in developing economies. Consumer interests should be of upper-most priority in the mind while establishing power markets and regulatory institutions, particularly as market forces are unfavorable to consumer interests in power shortage conditions. As competition fosters, gradually market forces take over and the ''harsh'' regulator would convert itself to a ''silent vigil referee'' so as to ensure genuine competition. The debate of deregulation vs. regulation will continue but the show must go on for building of an increasingly sound, competitive and vibrant power sector in the interest of end use consumers. The planned and phased restructuring though a delayed process is a preferred process and India is fully determined to achieve this

  4. Reliability evaluation of deregulated electric power systems for planning applications

    International Nuclear Information System (INIS)

    Ehsani, A.; Ranjbar, A.M.; Jafari, A.; Fotuhi-Firuzabad, M.

    2008-01-01

    In a deregulated electric power utility industry in which a competitive electricity market can influence system reliability, market risks cannot be ignored. This paper (1) proposes an analytical probabilistic model for reliability evaluation of competitive electricity markets and (2) develops a methodology for incorporating the market reliability problem into HLII reliability studies. A Markov state space diagram is employed to evaluate the market reliability. Since the market is a continuously operated system, the concept of absorbing states is applied to it in order to evaluate the reliability. The market states are identified by using market performance indices and the transition rates are calculated by using historical data. The key point in the proposed method is the concept that the reliability level of a restructured electric power system can be calculated using the availability of the composite power system (HLII) and the reliability of the electricity market. Two case studies are carried out over Roy Billinton Test System (RBTS) to illustrate interesting features of the proposed methodology

  5. Commercial banking in the conditions of deregulation vs. reregulation

    Directory of Open Access Journals (Sweden)

    Zaklan Damir

    2014-01-01

    Full Text Available This paper examines contemporary trends in commercial banking, confronting the stages of deregulation and reregulation in this field triggered by the global mortgage crisis. Under deregulatory conditions the competitive position of banks has toughened, and they reacted to it by intensifying: marketization, i.e. globalization, concentration, securitization and conglomeration, and by turning to the profit-oriented risk management of their activity. The contraction of their interest margin was thus neutralized by the reduction of operational costs and loss provisions, and by an increase in non-interest revenues, thereby maintaining banking profitability. The recent crisis has pinpointed the necessity of firmer regulation or reregulation of the banking sector, aimed at reducing its systemic risk, the most important aspect of which being the stricter international banking capital and liquidity standards, along with the requirement to adequately treat systemically important banks. Reregulation should strengthen capitalization and liquidity; mitigate the volume, concentration, internationalization and business dispersion, hence improving the supervision of the banking sector, implying its lower, yet more stable profitability. Such an impact of the adopted section of targeted regulatory measures has been indicated by higher liquidity, lower globalization, slower concentration and securitization, and stabilization-oriented risk management activities of today's banks. Their growth and profitability have shrunk.

  6. Deregulation and restructuring of the electric utility industry

    Energy Technology Data Exchange (ETDEWEB)

    Nixon, Hal [Utility Workers Union of America (UWUA), AFL-CIO, (United States)

    1997-12-31

    Federal and state policy makers are currently faced with the rapidly evolving issue of the restructuring and potential deregulation of the electric utility industry, a sector of the economy of huge importance through its sheer size and its impact on the daily life and livelihood of everyone. This paper describes eleven principles that must be adhered to in any restructuring of the electric industry. Adherence to the principle and positions outlined can help assure that the transition in this industry benefits all, not just a few, and that the general health and welfare of the people is protected and enhanced [Espanol] Los legisladores estatales y federales se estan enfrentando con el rapido y envolvente aspecto de la reestructuracion y desregulacion potencial de la industria electrica, un sector de la economia de enorme importancia por su tamano y su impacto en la vida diaria y los medios de vida. En esta ponencia se describen once principios y posiciones que deben ser considerados en cualquier reestructuracion de la industria electrica. El apego a los principios y posiciones comentados puede ayudar a asegurar que la transicion en esta industria deneficie a todos, no solo a unos cuantos, y que la salud general y bienestar de la gente sea protegida y mejorada

  7. Investment and deregulation in the electricity generation industry

    International Nuclear Information System (INIS)

    Peluchon, B.

    2007-12-01

    This work addresses the issue of investment in the electricity generation industry. As the analysis of many crisis which have affected electricity markets shows, there is a systematic under-investment in peak capacity. Electricity prices are not high enough to cover fixed costs of such generators, a phenomenon that has been dubbed 'missing money' in some recent papers (Stoft). The investment decisions of a duo-poly facing random demand are then compared to those of a public monopoly. The results are that no prices may be high enough to solve the 'missing money' problem, since the duo-poly is able to exercise market power in order to maximize his profit. This results systematically in fewer peak capacity in the duo-poly case than in the public monopoly case. This remains true in the case of a n-oligopoly. The necessity of designing a mechanism remunerating capacity is thus demonstrated. Capacity markets are then analysed in the light of those results. What appears is that operating reserves are a public good and, as such, prevents capacity markets to solve the 'missing money' problem. This casts a shadow on the pursuit of deregulation in the electricity industry. (author)

  8. Deregulation - precondition for distributed energy in the economies in transition

    International Nuclear Information System (INIS)

    Brendow, K.

    2001-01-01

    This paper holds that deregulation, i.e. restructuring, competition and privatisation, is the main precondition for a more pronounced development of distributed power (DP) in the economies in transition in central and eastern Europe. This, then, raises the question how far the electricity, gas, steam and heat generating industries have presently moved on their way towards more market-oriented frameworks, competition and private ownership. A good benchmark for measuring progress is the existence (or lack thereof), and nature, of regulatory regimes enabling fair competition among large centralised and small decentralised power, and between wholesale generators and distributors on the one hand and customers or ''autoproducers'' or power merchants on the other. The paper describes the regulatory models applied or contemplated in the winter 2000/2001 in the various countries of central and eastern Europe and identifies fifteen general issues that require attention and solution. With regard to DP, it concludes that a major upswing is unlikely to occur before 2005-2008. While technological options abound, the institutional frameworks for customer-owned competitive DP systems are only being contemplated at present and only rarely put in place.(author)

  9. Opportunities for privatization and alliances in a deregulated marketplace

    Energy Technology Data Exchange (ETDEWEB)

    Erling, J.M. [KPMG, Toronto, ON (Canada)

    1998-09-01

    The main implications for municipal electric utilities (MEUs) and businesses in a deregulated, open access energy market include a range of possible alternative business structures, constraints on choices, increased risks, the need to understand objectives, capabilities and capacity for bearing risks. The issue of what business MEUs are in, what services they provide and how those services should be delivered, was hotly debated. It was suggested that with increasing competition, the range of possible business structures and arrangements will widen significantly. The different public-private options available to MEUs are (1) the conventional tender process, (2) contracting out, (3) joint ventures with a private company, (4) franchising, (5) outsourcing of specific functions, (6) operating agreements, (7) lease arrangements, (8) build-operate-transfer options (BOTs), and (9) the full privatization scenario. It was noted that some forms of public-private partnerships are more suited to some businesses than others. Also, different partnership structures can be used in different parts of any business. Objectives for any partnership should include maximizing profitability, minimizing risk and promoting economic development but under competition. The ability to choose objectives will change significantly and the achievement of any of the objectives will be determined by the marketplace. Some guidelines on measuring success and on maximizing market value were offered. Global trends towards more unbundling and price transparency, more outsourcing to the private sector, more competition, less government, regulatory reform and blurring of the boundaries between utility sectors were predicted.

  10. A multi-channel stakeholder consultation process for transmission deregulation

    International Nuclear Information System (INIS)

    Gregory, Robin; Fischhoff, Baruch; Thorne, Sarah; Butte, Gordon

    2003-01-01

    Deregulating Ontario's energy market required designing a rate structure for transmission costs that previously had been bundled with other electricity services. The Ontario Hydro Networks Company (now called Hydro One Networks, or 'Hydro One') owns and operates the transmission lines. It sought input from a full spectrum of stakeholders in preparing a proposed rate structure for submission to the regulator, the Ontario Energy Board (OEB). Securing that input meant accommodating great differences in stakeholders' familiarity with the (often highly technical) issues of rate setting. Hydro One drew on recent developments in stakeholder processes, integrated assessment, and risk communication to create a multi-channel process for eliciting and responding to stakeholder input. That process included (a) detailed background documents, (b) dedicated briefings and workshops, (c) mental models interviews, (d) focused meetings, and (e) mail (and email) boxes. The process was coordinated with a formal expert model, summarizing the factors determining the multiple impacts of the rate structure and the regulatory process producing it. The model analyzed these impacts, structured communications, and organized inputs, in a comprehensive and coherent way. This process facilitated developing proposals that were both technically sound and widely accepted by stakeholders, including the OEB. The case study provides a model for addressing other problems requiring stakeholder input on complex technical issues. It contrasts with other consultative processes with a less formal structure for eliciting concerns, less ability to encourage learning, and greater emphasis on achieving consensus

  11. Natural gas market assessment ten years after deregulation

    International Nuclear Information System (INIS)

    1996-11-01

    Changes which have taken place in the Canadian natural gas market in the ten years since the gas market was de-regulated, were reviewed. A 1985 agreement created conditions for a competitive natural gas market. However, the National Energy Board ensured that the pipeline transmission sector of the gas industry would continue to be regulated because of its natural monopoly characteristics. Open non-discriminatory access was to be provided to all shippers on inter-provincial gas pipelines. One objective of this report was to provide the Board with the means of assuring itself that the market was operating in such a way that Canadian requirements for natural gas were being met at fair market prices. The report also provided a review of the major changes in the gas producing and transmission sector, and reviewed developments in gas markets and sales practices. The overall assessment was that the natural gas industry was efficient and responsive to the demands of the marketplace. 5 tabs., 30 figs

  12. Global implications of U.S. power deregulation

    International Nuclear Information System (INIS)

    Maschoff, D.C.

    1996-01-01

    With U.S. power deregulation remaining a topic that is dominating the entire North American energy marketplace, this paper provides an update of events occurring in U.S. electric power markets, offering some observations about changes due to increasing competition in electric power markets, and discusses some reasons why the events in U.S. electric power markets will soon transform global energy markets. How quickly is the move from local service territory to global markets proceeding? More than fifty U.S. utility companies with revenues of over $1 billion (U.S.) will soon be actively seeking and participating in global business opportunities. Using the same logic that led them to pursue utility initiatives nationally, U.S. utilities will use their core capabilities to compete in global energy services markets. In connection with these global initiatives, U.S. utilities will bring the same fuel-neutral, gas-electric perspective to international electric power and natural gas markets. (Author)

  13. Price-elastic demand in deregulated electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, Afzal S.

    2003-05-01

    The degree to which any deregulated market functions efficiently often depends on the ability of market agents to respond quickly to fluctuating conditions. Many restructured electricity markets, however, experience high prices caused by supply shortages and little demand-side response. We examine the implications for market operations when a risk-averse retailer's end-use consumers are allowed to perceive real-time variations in the electricity spot price. Using a market-equilibrium model, we find that price elasticity both increases the retailers revenue risk exposure and decreases the spot price. Since the latter induces the retailer to reduce forward electricity purchases, while the former has the opposite effect, the overall impact of price responsive demand on the relative magnitudes of its risk exposure and end-user price elasticity. Nevertheless, price elasticity decreases cumulative electricity consumption. By extending the analysis to allow for early settlement of demand, we find that forward stage end-user price responsiveness decreases the electricity forward price relative to the case with price-elastic demand only in real time. Moreover, we find that only if forward stage end-user demand is price elastic will the equilibrium electricity forward price be reduced.

  14. FACTS controllers and the deregulated electric utility environment

    International Nuclear Information System (INIS)

    Ooi, B. T.; Galiana, F. D.; McGillis, D.; Joos, G.; Marceau, R.

    1998-01-01

    The concept of Flexible AC Transmission Systems (FACTS) is explored and the potential of power electronic converters to increase flexibility and reliability of modern power systems is explored. Power electronic controllers can reduce the required safety margin in electric power generation capacity through the use of faster controllers based on exploiting the high-power solid-state switches with gate-turn-off capabilities. The FACTS concept makes it possible to postpone the financial investment needed to build more power lines, and also offers a solution to securing the right-of-way to build new lines. Currently available FACTS controllers such as the Static var Compensator (STATCOM) and the Unified Power Flow Controller (UPFC) are described, including their function, structure and relevant implementation issues. Since they can produce the required amount of reactive power independently of line voltage or current, and if equipped with energy storing devices they can supply real power as required, they are a necessary element for the control of power systems in a deregulated environment. 15 refs., 3 figs

  15. The impact of the deregulated electricity market on the future of nuclear energy

    International Nuclear Information System (INIS)

    Hennies, H.H.

    2000-01-01

    Deregulation means that the consumer may choose between different electricity suppliers. These have to pay for transmission through the net of other distributers. In Europe first steps to deregulation began in 1991 in Britain and Norway followed by Sweden and Finnland in 1996.Following a directive of the European Commission 12 out of 15 countries should have liberalized their markets until 1999. With the exception of France this took place. The German market was opened completely in 1999 with a high dynamic, resulting in price cuts for the industrial consumers by 30-50% and even for private households by 15- 20%. Without an increase of overall electricity consumption and with overcapacity of generating units, utilities try to increase their market shares in a highly competitive market. The price for the positive changes was a strict cost management in the German electricity industry with a reduction of 30 000 employees from about 230 000 before and a reduction of investments in generating and transmission. Today electricity is sold in the high voltage grid for 4-5 Pfg/kwh, leaving after reduction for transmission about 2-2,5 Pfg/kwh for production. New gasfired combined power plants (G+D) produce electricity for about 5 Pfg/kwh. Although always praised as the best performers, they cannot meet the tolerable price limit in Germany for base load. The same is true for new coal plants, as long as a large overcapacity exists. But existing nuclear plants are generating at marginal costs of about 1,5 Pfg/kwh. These written off plants have an excellent position in the market. Therefor the future of nuclear energy will not be the construction of new plants in the coming years but will be determined by the extension of the lifetime of existing plants, their improvement and safe operation. Because of the actual political opposition in Germany it is difficult to make previsions for a long term future. The cost and market considerations made for Germany should be valid for most

  16. TCSC based automatic generation control of deregulated power system using quasi-oppositional harmony search algorithm

    Directory of Open Access Journals (Sweden)

    Mahendra Nandi

    2017-08-01

    Full Text Available In present aspect, automatic generation control (AGC of deregulated power system with thyristor controlled series compensator (TCSC device is investigated. The objective is to discuss bilateral power transaction issue with the TCSC effect. A deregulated two-area power system model having two thermal units in each control area is considered for this act. A quasi-oppositional harmony search (QOHS algorithm is being applied for the constrained optimization problem. Three cases, commonly studied in deregulation, are discussed for the effectiveness of the proposed technique. Further, sensitivity analysis is studied by varying the test system parameters up to ±25% from their rated values. The obtained simulation plots are analytically discussed with the calculation of oscillatory modes, transient details and the studied performance indices. Sugeno fuzzy logic control technique is also investigated to the studied test system. The simulation results show that the proposed QOHS based TCSC controller is quite effective in deregulated environment.

  17. Regulatory Assessment of the Effects of Economic Deregulation of the Nuclear Industry

    International Nuclear Information System (INIS)

    2002-11-01

    The European Commission Nuclear Regulators Working Group (NRWG) appointed a Task Force (TF) to develop a common view among European regulators on the assessment of typical safety consequences resulting from economic pressure on operators as a result of deregulation of electricity markets. Although the report seems to imply that there are only negative aspects of deregulation, this is not the case. As the focus of the TF has been potential safety consequences we have not dealt with potential positive effects of deregulation. To provide a general background to the analyses of the safety consequences, the TF undertook a survey of the current situation within the EU and candidate countries on aspects of economic deregulation of the countries nuclear industry and the experiences so far of regulating these issues. Answers were submitted in of July 2001. 13 NRWG members with nuclear power plants took part in the survey. (author)

  18. Challenges for the nuclear safety of the deregulation of electricity markets

    International Nuclear Information System (INIS)

    2001-01-01

    Eurosafe 2000 was organised around two round tables on the first day and four seminars on the second day. The first round table dealt with general aspects of deregulation including the economic constraints and the special challenges arising during transition from regulated to deregulated structures. The second round table focussed on technical and organisational safety issues which are directly or indirectly related to the changes introduced by deregulation. The four seminars hold in order to provide opportunities for comparing experiences and learning about recent activities of IPSN, GRS and their partners in the European Union and Eastern Europe: Seminar 1 (Nuclear installation safety, assessment and analysis): assessment of the flooding incident at the Blayais nuclear power plant; PSA data base, comparison of the French and German approach; assessment of the Balakovo fire probabilistic study and elaboration of a guide for reviewing fire PSA; comprehensive technical assessment of an advanced German PWR by PSA - objectives and main results; PSA approach for the safety assessment of low-power and shutdown states; correlation of initiating events with the PSA level-2 results; safety assessment for fission products tests in the Phebus reactor; use of NPP simulators for applied human factor studies; assessment of the 'deterministic realistic method' applied to large LOCA analysis; assessment of the feasibility of an improvement programme enabling operation of units 3 and 4 of Kozloduy nuclear power plant. Seminar 2 (nuclear installation safety, research): PHEBUS 2K project on severe accidents; current status of the COCOSYS development; fission product modeling in ASTEC; Euratom Framework Programme (FP) research in reactor safety: main achievements of FP- 4 (1994-1998), some preliminary results of FP-5 (1998-2002) and prospects for beyond 2002; development of coupled systems of 3D neutronics and fluid-dynamic system codes and their application for safety analyses

  19. The limits to deregulation of entry and expansion of the US gas pipeline industry

    International Nuclear Information System (INIS)

    Rosput, P.G.

    1993-01-01

    US consumers of natural gas have enjoyed significant benefits as the pricing of the commodity has been deregulated. Thanks in large part to the success of deregulation of the natural gas commodity. US federal regulators have embarked upon a wide-ranging programme of eliminating barriers to entry and expansion of natural gas pipelines, which have traditionally been regulated as natural monopolies. As a result, there is now significant excess capacity in the natural gas transmission sector, without measurable benefits to consumers. (author)

  20. Market Power of Local Cable Television Franchises: Evidence from the Effects of Deregulation

    OpenAIRE

    Adam B. Jaffe; David M. Kanter

    1990-01-01

    The 1989 Cable Act eliminated most price regulation of cable television operators, including the right of municipalities to enforce price terms in franchise agreements. Deregulation was justified, at least partially, by the contention that competition from other entertainment media eliminated any market power of cable franchises. We examine the value at sale of existing cable systems before and after deregulation. Assuming that this value represents the expected present value of future profit...

  1. The Importance of Management in the Deregulated Retail Electricity Distribution Market in Slovenia

    OpenAIRE

    Drago Papler; Stefan Bojnec

    2006-01-01

    This paper underlines the importance of management in the deregulated retail electricity distribution market, entrepreneurship and business behaviours toward consumers’ satisfaction with quality of services. The coefficients of concentration indicate a high concentration of electricity suppliers and users in the deregulated electricity retail market for industry. The production function reveals the importance of education and electricity infrastructure, and to a lesser extent of capital inten...

  2. DAIRY DEREGULATION AND LOW-INPUT DAIRY PRODUCTION: A BIOECONOMIC EVALUATION

    OpenAIRE

    Tozer, Peter R.; Huffaker, Ray G.

    1999-01-01

    Deregulation of the Australian dairy industry could affect the utilization of resources by milk producers and the profitability of dairy production. In this study we examine the feed mix that dairy producers use, both pastures and supplements, under partial and total deregulation. We are particularly interested in the interaction of pasture utilization and farm profitability. The results of this research demonstrate that profitable low-input dairy is constrained by the most limiting resource,...

  3. Assessing the Significance of Telecommunication Deregulation on the Growth of Japan's Mobile Phone Market

    OpenAIRE

    Yuqing Xing

    2001-01-01

    This paper analyzes the development of Japan's mobile phone market. Specifically, it focuses on the regulatory reforms of Japan's mobile communication sector and their impact on the growth of the market. The analysis based on a monopolistic competition model shows that the deregulation policies perform an essential role in fostering the rapid expansion of Japan's mobile phone market. Using quarterly data from 1991 to 1999, the paper tests the significance of the telecommunication deregulation...

  4. Pomen managementa na dereguliranem maloprodajnem trgu električne energije v Sloveniji = The Importance of Management in the Deregulated Retail Electricity Distribution Market in Slovenia

    Directory of Open Access Journals (Sweden)

    Drago Papler

    2006-12-01

    Full Text Available This paper underlines the importance of management in the deregulated retail electricity distribution market, entrepreneurship and business behaviours toward consumers’ satisfaction with quality of services. The coefficients of concentration indicate a high concentration of electricity suppliers and users in the deregulated electricity retail market for industry. The production function reveals the importance of education and electricity infrastructure, and to a lesser extent of capital intensity, in labour productivity growth in the retail electricity distribution enterprise. Electricity demand in industry is determined positively by real income growth and negatively by real electricity price increases. Multivariate factor analysis confirms two main common components of efficient retail electricity supply and satisfaction of consumers in industry. In the first group of factors of efficient retail electricity supply the highest weights are for consumption, quality of services, expenses and advice. In the second group of factors of consumers’ satisfaction the highest weights are for response, needs, reliability and personnel. The impacts of changes in the dynamics of competition in the deregulated retail electricity market on management and organisational behaviours are found significant for quality of services, marketing and marketing strategies, supply-chain and customer relationship management.

  5. Transient phosphorylation of tumor associated microtubule associated protein (TMAP)/cytoskeleton associated protein 2 (CKAP2) at Thr-596 during early phases of mitosis.

    Science.gov (United States)

    Hong, Kyung Uk; Choi, Yong-Bock; Lee, Jung-Hwa; Kim, Hyun-Jun; Kwon, Hye-Rim; Seong, Yeon-Sun; Kim, Heung Tae; Park, Joobae; Bae, Chang-Dae; Hong, Kyeong-Man

    2008-08-31

    Tumor associated microtubule associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2) is a mitotic spindle-associated protein whose expression is cell cycle-regulated and also frequently deregulated in cancer cells. Two monoclonal antibodies (mAbs) against TMAP/CKAP2 were produced: B-1-13 and D-12-3. Interestingly, the reactivity of mAb D-12-3 to TMAP/CKAP2 was markedly decreased specifically in mitotic cell lysate. The epitope mapping study showed that mAb D-12-3 recognizes the amino acid sequence between 569 and 625 and that phosphorylation at T596 completely abolishes the reactivity of the antibody, suggesting that the differential reactivity originates from the phosphorylation status at T596. Immunofluorescence staining showed that mAb D-12-3 fails to detect TMAP/CKAP2 in mitotic cells between prophase and metaphase, but the staining becomes evident again in anaphase, suggesting that phosphorylation at T596 occurs transiently during early phases of mitosis. These results suggest that the cellular functions of TMAP/CKAP2 might be regulated by timely phosphorylation and dephosphorylation during the course of mitosis.

  6. Protein friction limits diffusive and directed movements of kinesin motors on microtubules.

    Science.gov (United States)

    Bormuth, Volker; Varga, Vladimir; Howard, Jonathon; Schäffer, Erik

    2009-08-14

    Friction limits the operation of macroscopic engines and is critical to the performance of micromechanical devices. We report measurements of friction in a biological nanomachine. Using optical tweezers, we characterized the frictional drag force of individual kinesin-8 motor proteins interacting with their microtubule tracks. At low speeds and with no energy source, the frictional drag was related to the diffusion coefficient by the Einstein relation. At higher speeds, the frictional drag force increased nonlinearly, consistent with the motor jumping 8 nanometers between adjacent tubulin dimers along the microtubule, and was asymmetric, reflecting the structural polarity of the microtubule. We argue that these frictional forces arise from breaking bonds between the motor domains and the microtubule, and they limit the speed and efficiency of kinesin.

  7. Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines.

    Science.gov (United States)

    Friel, Claire T; Howard, Jonathon

    2012-12-01

    The cycle of ATP turnover is integral to the action of motor proteins. Here we discuss how variation in this cycle leads to variation of function observed amongst members of the kinesin superfamily of microtubule associated motor proteins. Variation in the ATP turnover cycle among superfamily members can tune the characteristic kinesin motor to one of the range of microtubule-based functions performed by kinesins. The speed at which ATP is hydrolysed affects the speed of translocation. The ratio of rate constants of ATP turnover in relation to association and dissociation from the microtubule influence the processivity of translocation. Variation in the rate-limiting step of the cycle can reverse the way in which the motor domain interacts with the microtubule producing non-motile kinesins. Because the ATP turnover cycle is not fully understood for the majority of kinesins, much work remains to show how the kinesin engine functions in such a wide variety of molecular machines.

  8. Cytoplasmic Nucleation and Atypical Branching Nucleation Generate Endoplasmic Microtubules in Physcomitrella patens[OPEN

    Science.gov (United States)

    Nakaoka, Yuki; Kimura, Akatsuki; Tani, Tomomi; Goshima, Gohta

    2015-01-01

    The mechanism underlying microtubule (MT) generation in plants has been primarily studied using the cortical MT array, in which fixed-angled branching nucleation and katanin-dependent MT severing predominate. However, little is known about MT generation in the endoplasm. Here, we explored the mechanism of endoplasmic MT generation in protonemal cells of Physcomitrella patens. We developed an assay that utilizes flow cell and oblique illumination fluorescence microscopy, which allowed visualization and quantification of individual MT dynamics. MT severing was infrequently observed, and disruption of katanin did not severely affect MT generation. Branching nucleation was observed, but it showed markedly variable branch angles and was occasionally accompanied by the transport of nucleated MTs. Cytoplasmic nucleation at seemingly random locations was most frequently observed and predominated when depolymerized MTs were regrown. The MT nucleator γ-tubulin was detected at the majority of the nucleation sites, at which a single MT was generated in random directions. When γ-tubulin was knocked down, MT generation was significantly delayed in the regrowth assay. However, nucleation occurred at a normal frequency in steady state, suggesting the presence of a γ-tubulin-independent backup mechanism. Thus, endoplasmic MTs in this cell type are generated in a less ordered manner, showing a broader spectrum of nucleation mechanisms in plants. PMID:25616870

  9. Cytoplasmic streaming in Drosophila oocytes varies with kinesin activity and correlates with the microtubule cytoskeleton architecture.

    Science.gov (United States)

    Ganguly, Sujoy; Williams, Lucy S; Palacios, Isabel M; Goldstein, Raymond E

    2012-09-18

    Cells can localize molecules asymmetrically through the combined action of cytoplasmic streaming, which circulates their fluid contents, and specific anchoring mechanisms. Streaming also contributes to the distribution of nutrients and organelles such as chloroplasts in plants, the asymmetric position of the meiotic spindle in mammalian embryos, and the developmental potential of the zygote, yet little is known quantitatively about the relationship between streaming and the motor activity which drives it. Here we use Particle Image Velocimetry to quantify the statistical properties of Kinesin-dependent streaming during mid-oogenesis in Drosophila. We find that streaming can be used to detect subtle changes in Kinesin activity and that the flows reflect the architecture of the microtubule cytoskeleton. Furthermore, based on characterization of the rheology of the cytoplasm in vivo, we establish estimates of the number of Kinesins required to drive the observed streaming. Using this in vivo data as the basis of a model for transport, we suggest that the disordered character of transport at mid-oogenesis, as revealed by streaming, is an important component of the localization dynamics of the body plan determinant oskar mRNA.

  10. Multi scale modeling of 2450MHz electric field effects on microtubule mechanical properties.

    Science.gov (United States)

    Setayandeh, S S; Lohrasebi, A

    2016-11-01

    Microtubule (MT) rigidity and response to 2450MHz electric fields were investigated, via multi scale modeling approach. For this purpose, six systems were designed and simulated to consider all types of feasible interactions between α and β monomers in MT, by using all atom molecular dynamics method. Subsequently, coarse grain modeling was used to design different lengths of MT. Investigation of effects of external 2450MHz electric field on MT showed MT less rigidity in the presence of such field, which may perturb its functions. Moreover, an additional computational setup was designed to study effects of 2450MHz field on MT response to AFM tip. It was found, more tip velocity led to MT faster transformation and less time was required to change MT elastic response to plastic one, applying constant radius. Moreover it was observed smaller tip caused to increase required time to change MT elastic response to plastic one, considering constant velocity. Furthermore, exposing MT to 2450MHz field led to no significant changes in MT response to AFM tip, but quick change in MT elastic response to plastic one. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers

    Directory of Open Access Journals (Sweden)

    Hsieh Hsing-Pang

    2009-07-01

    Full Text Available Abstract Background Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent and paclitaxel (microtubule stabilizer in cancers. However, survivin-induced resistance to microtubule de-stabilizers such as Vinca alkaloids and Combretastatin A-4 (CA-4-related compounds were seldom demonstrated in the past. Furthermore, the question remains as to whether survivin plays a dominant role in processing cytokinesis or inhibiting caspases activity in cells treated with anti-mitotic compounds. The purpose of this study is to evaluate the effect of survivin on the resistance and susceptibility of human cancer cells to microtubule de-stabilizer-induced cell death. Results BPR0L075 is a CA-4 analog that induces microtubule de-polymerization and subsequent caspase-dependent apoptosis. To study the relationship between the expression of survivin and the resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer cell line, KB-L30, was generated for this study. Here, we found that survivin was over-expressed in the KB-L30 cells. Down-regulation of survivin by siRNA induced hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to BPR0L075 in KB-L30 cells. Western blot analysis revealed that down-regulation of survivin induced microtubule de-stabilization in both KB and KB-L30 cells. However, the same treatment did not enhance the down-stream caspase-3/-7 activities in BPR0L075-treated KB cells. Translocation of a caspase-independent apoptosis-related molecule, apoptosis-inducing factor (AIF, from cytoplasm to the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment. Conclusion In this study, survivin plays an important role in the

  12. Arabidopsis FH1 Formin Affects Cotyledon Pavement Cell Shape by Modulating Cytoskeleton Dynamics.

    Science.gov (United States)

    Rosero, Amparo; Oulehlová, Denisa; Stillerová, Lenka; Schiebertová, Petra; Grunt, Michal; Žárský, Viktor; Cvrčková, Fatima

    2016-03-01

    Plant cell morphogenesis involves concerted rearrangements of microtubules and actin microfilaments. We previously reported that FH1, the main Arabidopsis thaliana housekeeping Class I membrane-anchored formin, contributes to actin dynamics and microtubule stability in rhizodermis cells. Here we examine the effects of mutations affecting FH1 (At3g25500) on cell morphogenesis and above-ground organ development in seedlings, as well as on cytoskeletal organization and dynamics, using a combination of confocal and variable angle epifluorescence microscopy with a pharmacological approach. Homozygous fh1 mutants exhibited cotyledon epinasty and had larger cotyledon pavement cells with more pronounced lobes than the wild type. The pavement cell shape alterations were enhanced by expression of the fluorescent microtubule marker GFP-microtubule-associated protein 4 (MAP4). Mutant cotyledon pavement cells exhibited reduced density and increased stability of microfilament bundles, as well as enhanced dynamics of microtubules. Analogous results were also obtained upon treatments with the formin inhibitor SMIFH2 (small molecule inhibitor of formin homology 2 domains). Pavement cell shape in wild-type (wt) and fh1 plants in some situations exhibited a differential response towards anti-cytoskeletal drugs, especially the microtubule disruptor oryzalin. Our observations indicate that FH1 participates in the control of microtubule dynamics, possibly via its effects on actin, subsequently influencing cell morphogenesis and macroscopic organ development. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Protecting consumer interests in Alberta's deregulated electricity market

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    This paper explains why the province of Alberta decided to deregulate its electricity sector. In the early 1990s, electricity rates were reasonable in Alberta, there was no utility debt, and electricity costs were low. In 1994 California's open access transmission system suggested that open markets would result in lower electricity rates and attract new economic activity. The government of Alberta also believed that competitive markets would set prices with no need for economic regulation. In the initial transition to competition, regulated electricity rates were offered to customers who were not ready to switch to the new competitive market. The RRO rate was set by the Alberta Energy and Utilities Board (EUB). The rates included the forecasted cost of purchasing energy from markets, cost of system access, and retail service costs. The end of the RRO rate was scheduled for 2005 when the market was expected be well developed. This paper also describes other protection mechanisms for consumers. Alberta's new electricity policy (NEP) eliminates generator participant costs related to transmission. EUB's zonal interconnection charges are also overruled along with the EUB-approved 50/50 division of transmission costs. Under the NEP, the ISO is to build transmission in anticipation of new generation. Consumers will fund the total cost to build new transmission capacity for exports and imports. This new transmission policy is a complete change from the original government policy which allocated some transmission costs to generators. The sudden change in policy was due to pressure from oil sands producers and oil sands co-generation developers. The claimed benefit to Albertans is a 25 per cent reduction in pool price and greater system reliability. However, the author cautioned that government interference with competitive electricity markets will cripple the electric power industry in the foreseeable future because it interferes with market prices

  14. The deregulation connection : utility competition creates new niche company

    International Nuclear Information System (INIS)

    Roy, C.

    1999-01-01

    Deregulation in Ontario's utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network's capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs

  15. Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD, yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca(2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca(2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5, calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b, whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a and type 3 (PIT2 were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca(2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development.

  16. The deregulation connection : utility competition creates new niche company

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C

    1999-08-01

    Deregulation in Ontario's utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network's capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs.

  17. The deregulation connection : utility competition creates new niche company

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C.

    1999-08-01

    Deregulation in Ontario`s utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network`s capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs.

  18. Deregulation led to record-breaking profit for SPP

    International Nuclear Information System (INIS)

    Janoska, J.

    2004-01-01

    The state collected close to 15 bn Sk of SPP's last year profits. The income tax represents about 5,2 bn Sk and the dividends paid to state as owner of 51 percent of the stock of Slovensky plynarensky priemysel, a.s., Bratislava (SPP) amount up to 9,5 billion Sk. Investors Ruhrgas and Gaz de France will split 9 billion Sk. This was possible thank to a record-breaking net profit of 20.5 billion Sk made by the company due to deregulation of the distorted gas prices for consumers that lead to an average price increase by over 30 percent. A positive impact on the company's economy had also the dissolving of provisions and reserves but on the other hand the sales went down by close to 5 percent due to higher temperatures. Another factor that had a positive impact on the company revenues was the increase of gas volumes transported through the SPP network to Western Europe. Expenditures related to purchase of gas increased last year and not even the decrease USD exchange rates could eliminate the impact of increasing gas prices. The decrease of sales on the domestic market was one of the major factors that allowed the total cost to decrease on year-to-year basis by ten percent. A restructuring of SPP should bring along further savings but the company has not calculated the total effect of a restructuring yet. The strong positive impact the restructuring may have on the company should show in 2004 and later. Last year the company concentrated on savings in area of maintenance and repairs and this year it should be the procurement expenditures that should be decreased. The future economic result of the company would depend on several factors like exchange rates, sale volumes and price of natural gas. Oils prices have reached their new maximums and the gas prices, in general, follow the oil price

  19. Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.

    Directory of Open Access Journals (Sweden)

    Rimi Chakrabarti

    Full Text Available Curcumin has been widely investigated for its myriad cellular effects resulting in reduced proliferation of various eukaryotic cells including cancer cells and the human malaria parasite Plasmodium falciparum. Studies with human cancer cell lines HT-29, Caco-2, and MCF-7 suggest that curcumin can bind to tubulin and induce alterations in microtubule structure. Based on this finding, we investigated whether curcumin has any effect on P. falciparum microtubules, considering that mammalian and parasite tubulin are 83% identical. IC50 of curcumin was found to be 5 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM curcumin showed a concentration-dependent effect on parasite microtubules resulting in diffuse staining contrasting with the discrete hemispindles and subpellicular microtubules observed in untreated parasites. The effect on P. falciparum microtubules was evident only in the second cycle for both concentrations tested. This diffuse pattern of tubulin fluorescence in curcumin treated parasites was similar to the effect of a microtubule destabilizing drug vinblastine on P. falciparum. Molecular docking predicted the binding site of curcumin at the interface of alpha and beta tubulin, similar to another destabilizing drug colchicine. Data from predicted drug binding is supported by results from drug combination assays showing antagonistic interactions between curcumin and colchicine, sharing a similar binding site, and additive/synergistic interactions of curcumin with paclitaxel and vinblastine, having different binding sites. This evidence suggests that cellular effects of curcumin are at least, in part, due to its perturbing effect on P. falciparum microtubules. The action of curcumin, both direct and indirect, on P. falciparum microtubules is discussed.

  20. Interplay between microtubule bundling and sorting factors ensures acentriolar spindle stability during C. elegans oocyte meiosis.

    Directory of Open Access Journals (Sweden)

    Timothy J Mullen

    2017-09-01

    Full Text Available In many species, oocyte meiosis is carried out in the absence of centrioles. As a result, microtubule organization, spindle assembly, and chromosome segregation proceed by unique mechanisms. Here, we report insights into the principles underlying this specialized form of cell division, through studies of C. elegans KLP-15 and KLP-16, two highly homologous members of the kinesin-14 family of minus-end-directed kinesins. These proteins localize to the acentriolar oocyte spindle and promote microtubule bundling during spindle assembly; following KLP-15/16 depletion, microtubule bundles form but then collapse into a disorganized array. Surprisingly, despite this defect we found that during anaphase, microtubules are able to reorganize into a bundled array that facilitates chromosome segregation. This phenotype therefore enabled us to identify factors promoting microtubule organization during anaphase, whose contributions are normally undetectable in wild-type worms; we found that SPD-1 (PRC1 bundles microtubules and KLP-18 (kinesin-12 likely sorts those bundles into a functional orientation capable of mediating chromosome segregation. Therefore, our studies have revealed an interplay between distinct mechanisms that together promote spindle formation and chromosome segregation in the absence of structural cues such as centrioles.

  1. Hypothesis: NDL proteins function in stress responses by regulating microtubule organization.

    Science.gov (United States)

    Khatri, Nisha; Mudgil, Yashwanti

    2015-01-01

    N-MYC DOWNREGULATED-LIKE proteins (NDL), members of the alpha/beta hydrolase superfamily were recently rediscovered as interactors of G-protein signaling in Arabidopsis thaliana. Although the precise molecular function of NDL proteins is still elusive, in animals these proteins play protective role in hypoxia and expression is induced by hypoxia and nickel, indicating role in stress. Homology of NDL1 with animal counterpart N-MYC DOWNREGULATED GENE (NDRG) suggests similar functions in animals and plants. It is well established that stress responses leads to the microtubule depolymerization and reorganization which is crucial for stress tolerance. NDRG is a microtubule-associated protein which mediates the microtubule organization in animals by causing acetylation and increases the stability of α-tubulin. As NDL1 is highly homologous to NDRG, involvement of NDL1 in the microtubule organization during plant stress can also be expected. Discovery of interaction of NDL with protein kinesin light chain- related 1, enodomembrane family protein 70, syntaxin-23, tubulin alpha-2 chain, as a part of G protein interactome initiative encourages us to postulate microtubule stabilizing functions for NDL family in plants. Our search for NDL interactors in G protein interactome also predicts the role of NDL proteins in abiotic stress tolerance management. Based on published report in animals and predicted interacting partners for NDL in G protein interactome lead us to hypothesize involvement of NDL in the microtubule organization during abiotic stress management in plants.

  2. Emerging roles for microtubules in angiosperm pollen tube growth highlight new research cues

    Directory of Open Access Journals (Sweden)

    Alessandra eMoscatelli

    2015-02-01

    Full Text Available In plants, actin filaments have an important role in organelle movement and cytoplasmic streaming. Otherwise microtubules have a role in restricting organelles to specific areas of the cell and in maintaining organelle morphology. In somatic plant cells, microtubules also participate in cell division and morphogenesis, allowing cells to take their definitive shape in order to perform specific functions. In the latter case, microtubules influence assembly of the cell wall, controlling the delivery of enzymes involved in cellulose synthesis and of wall modulation material to the proper sites.In angiosperm pollen tubes, organelle movement is generally attributed to the acto-myosin system, the main role of which is in distributing organelles in the cytoplasm and in carrying secretory vesicles to the apex for polarized growth. Recent data on membrane trafficking suggests a role of microtubules in fine delivery and repositioning of vesicles to sustain pollen tube growth. This review examines the role of microtubules in secretion and endocytosis, highlighting new research cues regarding cell wall construction and pollen tube-pistil crosstalk, that help unravel the role of microtubules in polarized growth.

  3. ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, J.; Sindelar, C; Mulko, N; Collins, K; Kong, S; Hawley, R; Kull, F

    2009-01-01

    Segregation of nonexchange chromosomes during Drosophila melanogaster meiosis requires the proper function of NOD, a nonmotile kinesin-10. We have determined the X-ray crystal structure of the NOD catalytic domain in the ADP- and AMPPNP-bound states. These structures reveal an alternate conformation of the microtubule binding region as well as a nucleotide-sensitive relay of hydrogen bonds at the active site. Additionally, a cryo-electron microscopy reconstruction of the nucleotide-free microtubule-NOD complex shows an atypical binding orientation. Thermodynamic studies show that NOD binds tightly to microtubules in the nucleotide-free state, yet other nucleotide states, including AMPPNP, are weakened. Our pre-steady-state kinetic analysis demonstrates that NOD interaction with microtubules occurs slowly with weak activation of ADP product release. Upon rapid substrate binding, NOD detaches from the microtubule prior to the rate-limiting step of ATP hydrolysis, which is also atypical for a kinesin. We propose a model for NOD's microtubule plus-end tracking that drives chromosome movement.

  4. Actin and microtubule networks contribute differently to cell response for small and large strains

    Science.gov (United States)

    Kubitschke, H.; Schnauss, J.; Nnetu, K. D.; Warmt, E.; Stange, R.; Kaes, J.

    2017-09-01

    Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell’s response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (≤5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

  5. Change in consumer sensitivity to electricity prices in response to retail deregulation: A panel empirical analysis of the residential demand for electricity in the United States

    International Nuclear Information System (INIS)

    Nakajima, Tadahiro; Hamori, Shigeyuki

    2010-01-01

    About ten years have passed since the deregulation of the U.S. retail electricity market, and it is now generally accepted that the available data is adequate to quantitatively assess and compare conditions before and after deregulation. This study, therefore, estimates the changes in price elasticity in the residential electricity market to examine the changes, if any, in household sensitivity (as a result of retail electricity market deregulation policies) to residential electricity rates. Specifically, six types of panel data are prepared, based on three cross-sections-all states (except for Alaska and Hawaii) and the District of Columbia, deregulated states, and non-deregulated states-and two time series-the period before deregulation and the period after deregulation. The panel empirical analysis techniques are used to determine whether or not the variables are stationary, and to estimate price elasticity. We find that there is no substantial difference in the price elasticity between deregulated and non-deregulated states for both periods-before deregulation and after deregulation. Thus, it can be said that the deregulation of the retail electricity market has not made consumers more sensitive to electricity rates and that retail deregulation policies are not the cause of price elasticity differences between deregulated and non-deregulated states.

  6. Change in consumer sensitivity to electricity prices in response to retail deregulation. A panel empirical analysis of the residential demand for electricity in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Tadahiro [The Kansai Electric Power Company, Incorporated, 6-16, Nakanoshima 3-chome, Kita-Ku, Osaka 530-8270 (Japan); Hamori, Shigeyuki [Faculty of Economics, Kobe University 2-1, Rokkodai, Nada-Ku, Kobe 657-8501 (Japan)

    2010-05-15

    About ten years have passed since the deregulation of the U.S. retail electricity market, and it is now generally accepted that the available data is adequate to quantitatively assess and compare conditions before and after deregulation. This study, therefore, estimates the changes in price elasticity in the residential electricity market to examine the changes, if any, in household sensitivity (as a result of retail electricity market deregulation policies) to residential electricity rates. Specifically, six types of panel data are prepared, based on three cross-sections - all states (except for Alaska and Hawaii) and the District of Columbia, deregulated states, and non-deregulated states - and two time series - the period before deregulation and the period after deregulation. The panel empirical analysis techniques are used to determine whether or not the variables are stationary, and to estimate price elasticity. We find that there is no substantial difference in the price elasticity between deregulated and non-deregulated states for both periods - before deregulation and after deregulation. Thus, it can be said that the deregulation of the retail electricity market has not made consumers more sensitive to electricity rates and that retail deregulation policies are not the cause of price elasticity differences between deregulated and non-deregulated states. (author)

  7. Calmodulin immunolocalization to cortical microtubules is calcium independent

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.D.; Cyr, R.J.

    1992-12-31

    Calcium affects the stability of cortical microtubules (MTs) in lysed protoplasts. This calmodulin (CaM)-mediated interaction may provide a mechanism that serves to integrate cellular behavior with MT function. To test the hypothesis that CaM associates with these MTs, monoclonal antibodies were produced against CaM, and one (designated mAb1D10), was selected for its suitability as an immunocytochemical reagent. It is shown that CaM associates with the cortical Mats of cultured carrot (Daucus carota L.) and tobacco (Nicotiana tobacum L.) cells. Inasmuch as CaM interacts with calcium and affects the behavior of these Mats, we hypothesized that calcium would alter this association. To test this, protoplasts containing taxol-stabilized Mats were lysed in the presence of various concentrations of calcium and examined for the association of Cam with cortical Mats. At 1 {mu}M calcium, many protoplasts did not have CaM in association with the cortical Mats, while at 3.6 {mu}M calcium, this association was completely abolished. The results are discussed in terms of a model in which CaM associates with Mats via two types of interactions; one calcium dependent and one independent.

  8. Calmodulin immunolocalization to cortical microtubules is calcium independent

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.D.; Cyr, R.J.

    1992-01-01

    Calcium affects the stability of cortical microtubules (MTs) in lysed protoplasts. This calmodulin (CaM)-mediated interaction may provide a mechanism that serves to integrate cellular behavior with MT function. To test the hypothesis that CaM associates with these MTs, monoclonal antibodies were produced against CaM, and one (designated mAb1D10), was selected for its suitability as an immunocytochemical reagent. It is shown that CaM associates with the cortical Mats of cultured carrot (Daucus carota L.) and tobacco (Nicotiana tobacum L.) cells. Inasmuch as CaM interacts with calcium and affects the behavior of these Mats, we hypothesized that calcium would alter this association. To test this, protoplasts containing taxol-stabilized Mats were lysed in the presence of various concentrations of calcium and examined for the association of Cam with cortical Mats. At 1 [mu]M calcium, many protoplasts did not have CaM in association with the cortical Mats, while at 3.6 [mu]M calcium, this association was completely abolished. The results are discussed in terms of a model in which CaM associates with Mats via two types of interactions; one calcium dependent and one independent.

  9. Characterization of gold nanoparticle binding to microtubule filaments

    International Nuclear Information System (INIS)

    Zhou, Jing C.; Wang Xianghuai; Xue Mei; Xu Zheng; Hamasaki, Toshikazu; Yang, Yang; Wang Kang; Dunn, Bruce

    2010-01-01

    Microtubule (MT) protein filaments were used as templates for fabricating Au nanowires as a bottom-up approach for fabricating building blocks for future integrated circuits. Photochemical reduction methods were employed to form Au nanoparticles which bind and uniformly cover the MT filaments. Synthesis of the MT-templated Au nanowires was characterized using UV/vis spectroscopy and transmission electron microscopy (TEM). In addition, binding between the MT filaments and Au nanoparticles was investigated using surface enhanced Raman spectroscopy (SERS) and X-ray photoelectron spectroscopy (XPS) to establish the nature of the binding sites. A variety of functional groups were identified by SERS to interact with the Au including imidazole, sulfur, aromatic rings, amine, and carboxylate. The imidazole ring in the histidine is the most prominent functional group for Au binding. The results from these studies provide better understanding of the binding between Au and the biotemplate and give insight concerning methods to improve Au coverage for MT-templated Au nanowires.

  10. Halogenated auxins affect microtubules and root elongation in Lactuca sativa

    Science.gov (United States)

    Zhang, N.; Hasenstein, K. H.

    2000-01-01

    We studied the effect of 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA), a recently described root growth stimulator, and 5,6-dichloro-indole-3-acetic acid (DCIAA) on growth and microtubule (MT) organization in roots of Lactuca sativa L. DCIAA and indole-3-butyric acid (IBA) inhibited root elongation and depolymerized MTs in the cortex of the elongation zone, inhibited the elongation of stele cells, and promoted xylem maturation. Both auxins caused the plane of cell division to shift from anticlinal to periclinal. In contrast, TFIBA (100 micromolar) promoted elongation of primary roots by 40% and stimulated the elongation of lateral roots, even in the presence of IBA, the microtubular inhibitors oryzalin and taxol, or the auxin transport inhibitor naphthylphthalamic acid. However, TFIBA inhibited the formation of lateral root primordia. Immunostaining showed that TFIBA stabilized MTs orientation perpendicular to the root axis, doubled the cortical cell length, but delayed xylem maturation. The data indicate that the auxin-induced inhibition of elongation and swelling of roots results from reoriented phragmoplasts, the destabilization of MTs in elongating cells, and promotion of vessel formation. In contrast, TFIBA induced promotion of root elongation by enhancing cell length, prolonging transverse MT orientation, delaying cell and xylem maturation.

  11. Regulation of microtubule-based transport by MAP4

    Science.gov (United States)

    Semenova, Irina; Ikeda, Kazuho; Resaul, Karim; Kraikivski, Pavel; Aguiar, Mike; Gygi, Steven; Zaliapin, Ilya; Cowan, Ann; Rodionov, Vladimir

    2014-01-01

    Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect. PMID:25143402

  12. APC functions at the centrosome to stimulate microtubule growth.

    Science.gov (United States)

    Lui, Christina; Ashton, Cahora; Sharma, Manisha; Brocardo, Mariana G; Henderson, Beric R

    2016-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is multi-functional. APC is known to localize at the centrosome, and in mitotic cells contributes to formation of the mitotic spindle. To test whether APC contributes to nascent microtubule (MT) growth at interphase centrosomes, we employed MT regrowth assays in U2OS cells to measure MT assembly before and after nocodazole treatment and release. We showed that siRNA knockdown of full-length APC delayed both initial MT aster formation and MT elongation/regrowth. In contrast, APC-mutant SW480 cancer cells displayed a defect in MT regrowth that was unaffected by APC knockdown, but which was rescued by reconstitution of full-length APC. Our findings identify APC as a positive regulator of centrosome MT initial assembly and suggest that this process is disrupted by cancer mutations. We confirmed that full-length APC associates with the MT-nucleation factor γ-tubulin, and found that the APC cancer-truncated form (1-1309) also bound to γ-tubulin through APC amino acids 1-453. While binding to γ-tubulin may help target APC to the site of MT nucleation complexes, additional C-terminal sequences of APC are required to stimulate and stabilize MT growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Microtubules Enable the Planar Cell Polarity of Airway Cilia

    Science.gov (United States)

    Vladar, Eszter K.; Bayly, Roy D.; Sangoram, Ashvin; Scott, Matthew P.; Axelrod, Jeffrey D.

    2012-01-01

    Summary Background Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance. Results We show that Planar Cell Polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; non-autonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization. We find that basal bodies dock after polarity of PCP proteins is established, are polarized nearly simultaneously, and refinement of basal body/cilium orientation continues during airway epithelial development. Unique to mature multiciliated cells, we identify PCP-regulated, planar polarized MTs that originate from basal bodies and interact, via their plus ends, with membrane domains associated with the PCP proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia. Conclusions A conserved PCP pathway orients airway cilia by communicating polarity information from asymmetric membrane domains at the apical junctions, through MTs, to orient the MT and actin based network of ciliary basal bodies below the apical surface. PMID:23122850

  14. The effects of 60Co γ-ray irradiation on cytoplasmic microtubules of mouse macrophages and lymphocytes

    International Nuclear Information System (INIS)

    Li Qianqian; Mao Zijun; Yin Zhiwei; Hu Yumin

    1989-05-01

    The effects of 60 Co γ-ray irradiation on cytoplasmic microtubules of mouse macrophages and lymphocytes were investigated by immunofluorescence microscopy and scanning electron microscope. The results indicated. (1) microtubule organization of the irradiated cells remarkably differed from that of the control since the doses over 4 Gy; (2) 144 hours after irradiation the alterations of microtubules have been shown to be basically r epaired ; (3) the cytoplasmic microtubules and centrioles disappeared under transmission electron microscope, the membranes irradiated and microvilli showed changes under scanning electron microscope too. From these observations and those of other workers who studied the radiation effect on extracted microtubule proteins in vitro, the authors support that 60 Co γ-ray irradiation can inhabits cytoplasmic microtubule assembling

  15. Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

    Science.gov (United States)

    Hur, Eun-Mi; Lee, Byoung Dae

    2014-12-01

    Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  16. Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

    Directory of Open Access Journals (Sweden)

    Eun-Mi Hur

    2014-12-01

    Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  17. The plant formin AtFH4 interacts with both actin and microtubules, and contains a newly identified microtubule-binding domain

    Czech Academy of Sciences Publication Activity Database

    Deeks, M.J.; Fendrych, Matyáš; Smertenko, A.; Bell, K.S.; Oparka, K.; Cvrčková, F.; Žárský, Viktor; Hussey, P.J.

    2010-01-01

    Roč. 123, č. 8 (2010), s. 1209-1215 ISSN 0021-9533 R&D Projects: GA MŠk(CZ) LC06004; GA ČR GAP305/10/0433 Institutional research plan: CEZ:AV0Z50380511 Keywords : Actin regulating proteins * Membrane * Microtubule Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.290, year: 2010

  18. Pricing behaviour of pharmacies after market deregulation for OTC drugs: the case of Germany.

    Science.gov (United States)

    Stargardt, Tom; Schreyögg, Jonas; Busse, Reinhard

    2007-11-01

    To examine the price reactions of German pharmacies to changes made to OTC drug regulations in 2004. Prior to these changes, regulations guaranteed identical prices in all German pharmacies. Two years after market deregulation, 256 pharmacies were surveyed to determine the retail prices of five selected OTC drugs. A probit regression model was used to identify factors that increased the likelihood of price changes. In addition, 409 pharmacy consumers were interviewed to gather information on their knowledge of the regulatory changes and to better explain consumer behaviour. Data was collected on a total of 1215 prices. Two years after deregulation, 23.1% of the participating pharmacies had modified the price of at least one of the five OTCs included in our study. However, in total, only 7.5% of the prices differed from their pre-deregulation level. The probit model showed that population density and the geographic concentration of pharmacies were significantly associated with price changes. Interestingly, the association with the geographic concentration of pharmacies was negative. The consumer survey revealed that 47.1% of those interviewed were aware of the deregulation. Our findings indicate that, two years after deregulation, very few pharmacies had made use of individual pricing strategies; price competition between pharmacies in Germany is thus taking place only a very small scale.

  19. The deregulation of electricity and gas markets. The great economic challenges

    International Nuclear Information System (INIS)

    Mirabel, Francois; Guerassimoff, Gilles

    2012-01-01

    As the process of deregulation of electricity and gas markets started in Europe ten years ago, this book aims at recalling and describing the consequences of this evolution, notably for companies which were in a monopoly situation for electricity and gas production, transport, retailing and selling, but also in terms of new entities to be created and of entities having to give up their specialty. The author first presents the economic characteristics of gas and electricity industries in terms of infrastructures and final services, scale, coordination and size of energy networks, of existence of strong externalities in networks, of commitment in public service missions. He describes the background and implementation of this deregulation. He analyses the strategies of companies and how energy markets are controlled: strategies to mitigate competition and to strengthen their market power, firm strategies and public policies, merging strategies, strategies of competition distortion. The last chapter addresses the various priority fields of deregulation: public service missions in a deregulated environment (issues of service continuity and of affordable prices), the environmental constraint in energy market organisation (limitation of CO 2 emissions, promotion of renewable energies, and reduction of energy consumption). In conclusion, the author discusses how to conciliate deregulation and sustainable development of energy

  20. Chlorpyrifos, chlorpyrifos-oxon, and diisopropylfluorophosphate inhibit kinesin-dependent microtubule motility

    International Nuclear Information System (INIS)

    Gearhart, Debra A.; Sickles, Dale W.; Buccafusco, Jerry J.; Prendergast, Mark A.; Terry, Alvin V.

    2007-01-01

    Diisopropylfluorophosphate, originally developed as a chemical warfare agent, is structurally similar to nerve agents, and chlorpyrifos has extensive worldwide use as an agricultural pesticide. While inhibition of cholinesterases underlies the acute toxicity of these organophosphates, we previously reported impaired axonal transport in the sciatic nerves from rats treated chronically with subthreshold doses of chlorpyrifos. Those data indicate that chlorpyrifos (and/or its active metabolite, chlorpyrifos-oxon) might directly affect the function of kinesin and/or microtubules-the principal proteins that mediate anterograde axonal transport. The current report describes in vitro assays to assess the concentration-dependent effects of chlorpyrifos (0-10 μM), chlorpyrifos-oxon (0-10 μM), and diisopropylfluorophosphate (0-0.59 nM) on kinesin-dependent microtubule motility. Preincubating bovine brain microtubules with the organophosphates did not alter kinesin-mediated microtubule motility. In contrast, preincubation of bovine brain kinesin with diisopropylfluorophosphate, chlorpyrifos, or chlorpyrifos-oxon produced a concentration-dependent increase in the number of locomoting microtubules that detached from the kinesin-coated glass cover slip. Our data suggest that the organophosphates-chlorpyrifos-oxon, chlorpyrifos, and diisopropylfluorophosphate-directly affect kinesin, thereby disrupting kinesin-dependent transport on microtubules. Kinesin-dependent movement of vesicles, organelles, and other cellular components along microtubules is fundamental to the organization of all eukaryotic cells, especially in neurons where organelles and proteins synthesized in the cell body must move down long axons to pre-synaptic sites in nerve terminals. We postulate that disruption of kinesin-dependent intracellular transport could account for some of the long-term effects of organophosphates on the peripheral and central nervous system