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Sample records for motor proteins kif1a

  1. Traffic of single-headed motor proteins KIF1A: effects of lane changing

    CERN Document Server

    Chowdhury, Debashish

    2007-01-01

    Kinesins are biomolecular motors which move on cylindrical nano-tubes called microtubules. A normal microtubule consists of more than one protofilament on which the equispaced motor binding sites form a periodic array. The collective movement of the kinesins on a microtubule is, therefore, analogous to vehicular traffic on multi-lane highways where each protofilament is the analogue of a single lane. We extend a recent model of the traffic of single-headed kinesin KIF1A [{\\it Phys. Rev. E {\\bf 75}, 041905 (2007)}] by incorporating processes which correspond to shifting of the motor proteins from one protofilament to another. On the basis of analytical treatment of our model, we predict the effects of lane changing on the flux of the KIF1A motors. Our quantitative predictions can be tested, in principle, by carrying out {\\it in-vitro} experiments with fluorescently labelled KIF1A molecules.

  2. Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus.

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    Filipa I Baptista

    Full Text Available Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM or mannitol (osmotic control; 25 mM plus 25 mM glucose for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal

  3. Stochastic kinetics of a single headed motor protein: dwell time distribution of KIF1A

    CERN Document Server

    Garai, Ashok

    2010-01-01

    KIF1A, a processive single headed kinesin superfamily motor, hydrolyzes Adenosine triphosphate (ATP) to move along a filamentous track called microtubule. The stochastic movement of KIF1A on the track is characterized by an alternating sequence of pause and translocation. The sum of the durations of pause and the following translocation defines the dwell time at the binding site on the microtubule. Using the NOSC model (Nishinari et. al. PRL, {\\bf 95}, 118101 (2005)), which captures the Brownian ratchet mechanism of individual KIF1A along with its biochemical cycle, we systematically derive an analytical expression for the dwell time distribution. In principle, our theoretical prediction can be tested by carrying out single-molecule experiments with adequate spatio-temporal resolution.

  4. Effect of microtubule-associated protein tau in dynamics of single-headed motor proteins KIF1A

    CERN Document Server

    Sparacino, J; Lamberti, P W

    2013-01-01

    Intracellular transport based on molecular motors and its regulation are crucial to the functioning of cells. Filamentary tracks of the cells are abundantly decorated with non-motile microtubule-associated proteins, such as tau. Motivated by experiments on kinesin-tau interactions [Dixit et al. Science 319, 1086 (2008)] we developed a stochastic model of interacting single-headed motor proteins KIF1A that also takes into account the interactions between motor proteins and tau molecules. Our model reproduce experimental observations and predicts significant effects of tau on bound time and run length which suggest an important role of tau in regulation of kinesin-based transport.

  5. Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia.

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    Ylikallio, Emil; Kim, Doyoun; Isohanni, Pirjo; Auranen, Mari; Kim, Eunjoon; Lönnqvist, Tuula; Tyynismaa, Henna

    2015-10-01

    Variants in family 1 kinesin (KIF1A), which encodes a kinesin axonal motor protein, have been described to cause variable neurological manifestations. Recessive missense variants have led to spastic paraplegia, and recessive truncations to sensory and autonomic neuropathy. De novo missense variants cause developmental delay or intellectual disability, cerebellar atrophy and variable spasticity. We describe a family with father-to-son transmission of de novo variant in the KIF1A motor domain, in a phenotype of pure spastic paraplegia. Structural modeling of the predicted p.(Ser69Leu) amino acid change suggested that it impairs the stable binding of ATP to the KIF1A protein. Our study reports the first dominantly inherited KIF1A variant and expands the spectrum of phenotypes caused by heterozygous KIF1A motor domain variants to include pure spastic paraplegia. We conclude that KIF1A should be considered a candidate gene for hereditary paraplegias regardless of inheritance pattern.

  6. The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function.

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    Tanaka, Yosuke; Niwa, Shinsuke; Dong, Ming; Farkhondeh, Atena; Wang, Li; Zhou, Ruyun; Hirokawa, Nobutaka

    2016-06-15

    KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway.

  7. De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy

    NARCIS (Netherlands)

    Lee, Jae Ran; Srour, Myriam; Kim, Doyoun; Hamdan, Fadi F.; Lim, So Hee; Brunel-Guitton, Catherine; Décarie, Jean Claude; Rossignol, Elsa; Mitchell, Grant A.; Schreiber, Allison; Moran, Rocio; Van Haren, Keith; Richardson, Randal; Nicolai, Joost; Oberndorff, Karin M E J; Wagner, Justin D.; Boycott, Kym M.; Rahikkala, Elisa; Junna, Nella; Tyynismaa, Henna; Cuppen, Inge; Verbeek, Nienke E.; Stumpel, Connie T R M; Willemsen, Michel A.; de Munnik, Sonja A.; Rouleau, Guy A.; Kim, Eunjoon; Kamsteeg, Erik Jan; Kleefstra, Tjitske; Michaud, Jacques L.

    2015-01-01

    KIF1A is a neuron-specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type-2. Here, we report 11 heterozygous de novo missense mutations (p

  8. Cooperative action of KIF1A Brownian motors with finite dwell time

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    Oriola, David; Casademunt, Jaume

    2014-03-01

    We study in detail the cooperative action of small groups of KIF1A motors in its monomeric (single-headed) form within an arrangement relevant to vesicle traffic or membrane tube extraction. It has been recently shown that under these circumstances, the presence of a finite dwell time in the motor cycle contributes to remarkably enhance collective force generation [D. Oriola and J. Casademunt, Phys. Rev. Lett. 111, 048103 (2013), 10.1103/PhysRevLett.111.048103]. We analyze this mechanism in detail by means of a two-state noise-driven ratchet model with hard-core repulsive interactions. We obtain staircase-shaped velocity-force curves and show that motors self-organize in clusters with a nontrivial force distribution that conveys a large part of the load to the central motors. Under heavy loads, large clusters adopt a synchronic mode of totally asymmetric steps. We also find a dramatic increase of the collective efficiency with the number of motors. Finally, we complete the study by addressing different interactions that impose spatial constraints such as rigid coupling and raft-induced confinement. Our results reinforce the hypothesis that the specificity of KIF1A to axonal vesicular transport may be deeply related to its high cooperativity.

  9. A non-Markov ratchet model of molecular motors: processive movement of single-headed kinesin KIF1A

    Institute of Scientific and Technical Information of China (English)

    Xie Ping; Dou Shuo-Xing; Wang Peng-Ye

    2006-01-01

    A fluctuating ratchet model of non-Markov process is presented to describe the processive movement of molecular motors of single-headed kinesin KIF1A, where the fluctuation perturbation to the local potential is introduced and the detailed ATPase pathway of the motor is included. The theoretical results show good quantitative agreement with the previous experimental ones.

  10. The Caenorhabditis elegans Kinesin-3 motor UNC-104/KIF1A is degraded upon loss of specific binding to cargo.

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    Jitendra Kumar

    2010-11-01

    Full Text Available UNC-104/KIF1A is a Kinesin-3 motor that transports synaptic vesicles from the cell body towards the synapse by binding to PI(4,5P(2 through its PH domain. The fate of the motor upon reaching the synapse is not known. We found that wild-type UNC-104 is degraded at synaptic regions through the ubiquitin pathway and is not retrogradely transported back to the cell body. As a possible means to regulate the motor, we tested the effect of cargo binding on UNC-104 levels. The unc-104(e1265 allele carries a point mutation (D1497N in the PI(4,5P(2 binding pocket of the PH domain, resulting in greatly reduced preferential binding to PI(4,5P(2in vitro and presence of very few motors on pre-synaptic vesicles in vivo. unc-104(e1265 animals have poor locomotion irrespective of in vivo PI(4,5P(2 levels due to reduced anterograde transport. Moreover, they show highly reduced levels of UNC-104 in vivo. To confirm that loss of cargo binding specificity reduces motor levels, we isolated two intragenic suppressors with compensatory mutations within the PH domain. These show partial restoration of in vitro preferential PI(4,5P(2 binding and presence of more motors on pre-synaptic vesicles in vivo. These animals show improved locomotion dependent on in vivo PI(4,5P(2 levels, increased anterograde transport, and partial restoration of UNC-104 protein levels in vivo. For further proof, we mutated a conserved residue in one suppressor background. The PH domain in this triple mutant lacked in vitro PI(4,5P(2 binding specificity, and the animals again showed locomotory defects and reduced motor levels. All allelic variants show increased UNC-104 levels upon blocking the ubiquitin pathway. These data show that inability to bind cargo can target motors for degradation. In view of the observed degradation of the motor in synaptic regions, this further suggests that UNC-104 may get degraded at synapses upon release of cargo.

  11. Intra-cellular transport by single-headed kinesin KIF1A: effects of single-motor mechano-chemistry and steric interactions

    CERN Document Server

    Greulich, P; Garai, A; Nishinari, K; Schadschneider, A; Chowdhury, Debashish; Garai, Ashok; Greulich, Philip; Nishinari, Katsuhiro; Schadschneider, Andreas

    2006-01-01

    In eukaryotic cells, many motor proteins can move simultaneously on a single microtubule track. This leads to interesting collective phenomena like jamming. Recently we reported ({\\it Phys. Rev. Lett. {\\bf 95}, 118101 (2005)}) a lattice-gas model which describes traffic of unconventional (single-headed) kinesins KIF1A. Here we generalize this model, introducing a novel interaction parameter $c$, to account for an interesting mechano-chemical process which has not been considered in any earlier model. We have been able to extract all the parameters of the model, except $c$, from experimentally measured quantities. In contrast to earlier models of intra-cellular molecular motor traffic, our model assigns distinct ``chemical'' (or, conformational) states to each kinesin to account for the hydrolysis of ATP, the chemical fuel of the motor. Our model makes experimentally testable theoretical predictions. We determine the phase diagram of the model in planes spanned by experimentally controllable parameters, namely...

  12. The KIF1A homolog Unc-104 is important for spontaneous release, postsynaptic density maturation and perisynaptic scaffold organization

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    Zhang, Yao V.; Hannan, Shabab B.; Kern, Jeannine V.; Stanchev, Doychin T.; Koç, Baran; Jahn, Thomas R.; Rasse, Tobias M.

    2017-01-01

    The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104bris, impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot. Here, we show that the unc-104brismutation causes defects in synaptic transmission as manifested by reduced amplitude of both evoked and miniature excitatory junctional potentials. Structural defects observed in the postsynaptic compartment of mutant NMJs include reduced glutamate receptor field size, and altered glutamate receptor composition. In addition, we observed marked loss of postsynaptic scaffolding proteins and reduced complexity of the sub-synaptic reticulum, which could be rescued by pre- but not postsynaptic expression of unc-104. Our results highlight the importance of kinesin-3 based axonal transport in synaptic transmission and provide novel insights into the role of Unc-104 in synapse maturation. PMID:28344334

  13. Formation of helical membrane tubes around microtubules by single-headed kinesin KIF1A

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    Oriola, David; Roth, Sophie; Dogterom, Marileen; Casademunt, Jaume

    2015-08-01

    The kinesin-3 motor KIF1A is in charge of vesicular transport in neuronal axons. Its single-headed form is known to be very inefficient due to the presence of a diffusive state in the mechanochemical cycle. However, recent theoretical studies have suggested that these motors could largely enhance force generation by working in teams. Here we test this prediction by challenging single-headed KIF1A to extract membrane tubes from giant vesicles along microtubule filaments in a minimal in vitro system. Remarkably, not only KIF1A motors are able to extract tubes but they feature a novel phenomenon: tubes are wound around microtubules forming tubular helices. This finding reveals an unforeseen combination of cooperative force generation and self-organized manoeuvreing capability, suggesting that the diffusive state may be a key ingredient for collective motor performance under demanding traffic conditions. Hence, we conclude that KIF1A is a genuinely cooperative motor, possibly explaining its specificity to axonal trafficking.

  14. Sub-cellular distribution of UNC-104(KIF1A) upon binding to adaptors as UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-α) in C. elegans neurons.

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    Hsu, C-C; Moncaleano, J D; Wagner, O I

    2011-03-10

    The accumulation of cargo (tau, amyloid precursor protein, neurofilaments etc.) in neurons is a hallmark of various neurodegenerative diseases while we have only little knowledge how axonal transport is regulated. Kinesin-3 UNC-104(KIF1A) is the major transporter of synaptic vesicles and recent reports suggest that a cargo itself can affect the motor's activity. Inspecting an interactome map, we identify three putative UNC-104 interactors, namely UNC-16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-α), known to be adaptors in essential neuronal protein complexes. We then employed the novel method bimolecular fluorescence complementation (BiFC) assay to visualize motor-adaptor complexes in the nervous system of living C. elegans. Interestingly, the binding of UNC-104 to each adaptor protein results in different sub-cellular distributions and has distinctive effects on the motor's motility. Specifically, if UNC-104 bound to UNC-16, the motor is primarily localized in the soma of neurons while bound to DNC-1, the motor is basically found in axonal termini. On the other hand, if UNC-104 is bound to SYD-2 we identify motor populations mostly along axons. Therefore, these three adaptors inherit different functions in steering the motor to specific sub-cellular locations in the neuron.

  15. Physics of protein motility and motor proteins

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    Kolomeisky, Anatoly B.

    2013-09-01

    Motor proteins are enzymatic molecules that transform chemical energy into mechanical motion and work. They are critically important for supporting various cellular activities and functions. In the last 15 years significant progress in understanding the functioning of motor proteins has been achieved due to revolutionary breakthroughs in single-molecule experimental techniques and strong advances in theoretical modelling. However, microscopic mechanisms of protein motility are still not well explained, and the collective efforts of many scientists are needed in order to solve these complex problems. In this special section the reader will find the latest advances on the difficult road to mapping motor proteins dynamics in various systems. Recent experimental developments have allowed researchers to monitor and to influence the activity of single motor proteins with a high spatial and temporal resolution. It has stimulated significant theoretical efforts to understand the non-equilibrium nature of protein motility phenomena. The latest results from all these advances are presented and discussed in this special section. We would like to thank the scientists from all over the world who have reported their latest research results for this special section. We are also grateful to the staff and editors of Journal of Physics: Condensed Matter for their invaluable help in handling all the administrative and refereeing activities. The field of motor proteins and protein motility is fast moving, and we hope that this collection of articles will be a useful source of information in this highly interdisciplinary area. Physics of protein motility and motor proteins contents Physics of protein motility and motor proteinsAnatoly B Kolomeisky Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116 Yuan Zhang, Mirkó Palla, Andrew Sun and Jung-Chi Liao The load dependence of the physical properties of a molecular motor

  16. Motor protein accumulation on antiparallel microtubule overlaps

    CERN Document Server

    Kuan, Hui-Shun

    2015-01-01

    Biopolymers serve as one-dimensional tracks on which motor proteins move to perform their biological roles. Motor protein phenomena have inspired theoretical models of one-dimensional transport, crowding, and jamming. Experiments studying the motion of Xklp1 motors on reconstituted antiparallel microtubule overlaps demonstrated that motors recruited to the overlap walk toward the plus end of individual microtubules and frequently switch between filaments. We study a model of this system that couples the totally asymmetric simple exclusion process (TASEP) for motor motion with switches between antiparallel filaments and binding kinetics. We determine steady-state motor density profiles for fixed-length overlaps using exact and approximate solutions of the continuum differential equations and compare to kinetic Monte Carlo simulations. The center region, far from the overlap ends, has a constant motor density as one would na\\"ively expect. However, rather than following a simple binding equilibrium, the center ...

  17. Molecular Motor Proteins and Amyotrophic Lateral Sclerosis

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    Manal Farg

    2011-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder affecting motor neurons in the brain, brainstem and spinal cord, which is characterized by motor dysfunction, muscle dystrophy and progressive paralysis. Both inherited and sporadic forms of ALS share common pathological features, however, the initial trigger of neurodegeneration remains unknown. Motor neurons are uniquely targeted by ubiquitously expressed proteins in ALS but the reason for this selectively vulnerability is unclear. However motor neurons have unique characteristics such as very long axons, large cell bodies and high energetic metabolism, therefore placing high demands on cellular transport processes. Defects in cellular trafficking are now widely reported in ALS, including dysfunction to the molecular motors dynein and kinesin. Abnormalities to dynein in particular are linked to ALS, and defects in dynein-mediated axonal transport processes have been reported as one of the earliest pathologies in transgenic SOD1 mice. Furthermore, dynein is very highly expressed in neurons and neurons are particularly sensitive to dynein dysfunction. Hence, unravelling cellular transport processes mediated by molecular motor proteins may help shed light on motor neuron loss in ALS.

  18. How Linear Motor Proteins Work

    Science.gov (United States)

    Oiwa, K.; Manstein, D. J.

    Most animals perform sophisticated forms of movement such as walking, running, flying and swimming using their skeletal muscles. Although directed movement is not generally associated with plants, cytoplasmic streaming in plant cells can reach velocities greater than 50 μm/s and thus constitutes one of the fastest forms of directed movement. Unicellular eukaryotic organisms and prokaryotes display diverse mechanisms by which they are able to actively move towards a food source, light or other sensory stimuli. On the cellular level active transport of vesicles and organelles is required, since the cytoplasm resembles a gel with a mesh size of approximately 50 nm, which makes the passive transport of organelle-sized particles impossible. For elongated cells such as neurons, even proteins and small metabolites have to be actively transported.

  19. Synapse-Assembly Proteins Maintain Synaptic Vesicle Cluster Stability and Regulate Synaptic Vesicle Transport in Caenorhabditis elegans.

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    Edwards, Stacey L; Yorks, Rosalina M; Morrison, Logan M; Hoover, Christopher M; Miller, Kenneth G

    2015-09-01

    The functional integrity of neurons requires the bidirectional active transport of synaptic vesicles (SVs) in axons. The kinesin motor KIF1A transports SVs from somas to stable SV clusters at synapses, while dynein moves them in the opposite direction. However, it is unclear how SV transport is regulated and how SVs at clusters interact with motor proteins. We addressed these questions by isolating a rare temperature-sensitive allele of Caenorhabditis elegans unc-104 (KIF1A) that allowed us to manipulate SV levels in axons and dendrites. Growth at 20° and 14° resulted in locomotion rates that were ∼3 and 50% of wild type, respectively, with similar effects on axonal SV levels. Corresponding with the loss of SVs from axons, mutants grown at 14° and 20° showed a 10- and 24-fold dynein-dependent accumulation of SVs in their dendrites. Mutants grown at 14° and switched to 25° showed an abrupt irreversible 50% decrease in locomotion and a 50% loss of SVs from the synaptic region 12-hr post-shift, with no further decreases at later time points, suggesting that the remaining clustered SVs are stable and resistant to retrograde removal by dynein. The data further showed that the synapse-assembly proteins SYD-1, SYD-2, and SAD-1 protected SV clusters from degradation by motor proteins. In syd-1, syd-2, and sad-1 mutants, SVs accumulate in an UNC-104-dependent manner in the distal axon region that normally lacks SVs. In addition to their roles in SV cluster stability, all three proteins also regulate SV transport.

  20. Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids

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    Choudhury, Pabitra Pal; Jana, Siddhartha Sankar

    2016-01-01

    Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na+/K+-ATPase and Ca2+-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins. PMID:27930687

  1. Motor proteins and molecular motors: how to operate machines at the nanoscale.

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    Kolomeisky, Anatoly B

    2013-11-20

    Several classes of biological molecules that transform chemical energy into mechanical work are known as motor proteins or molecular motors. These nanometer-sized machines operate in noisy stochastic isothermal environments, strongly supporting fundamental cellular processes such as the transfer of genetic information, transport, organization and functioning. In the past two decades motor proteins have become a subject of intense research efforts, aimed at uncovering the fundamental principles and mechanisms of molecular motor dynamics. In this review, we critically discuss recent progress in experimental and theoretical studies on motor proteins. Our focus is on analyzing fundamental concepts and ideas that have been utilized to explain the non-equilibrium nature and mechanisms of molecular motors.

  2. Pushing, pulling and trapping - Modes of motor protein supported protein translocation

    NARCIS (Netherlands)

    Tomkiewicz, Danuta; Nouwen, Nico; Driessen, Arnold J. M.

    2007-01-01

    Protein translocation across the cellular membranes is an ubiquitous and crucial activity of cells. This process is mediated by translocases that consist of a protein conducting channel and an associated motor protein. Motor proteins interact with protein substrates and utilize the free energy of

  3. Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

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    Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

    2012-06-20

    The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

  4. Multiscale modeling and simulation of microtubule–motor-protein assemblies

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

    2016-01-01

    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. PMID:26764729

  5. Dynamical model of the kinesin protein motor

    CERN Document Server

    Nesterov, Alexander I; Ramírez, Mónica F

    2016-01-01

    We model and simulate the stepping dynamics of the kinesin motor including electric and mechanical forces, environmental noise, and the complicated potentials produced by tracking and neighboring protofilaments. Our dynamical model supports the hand-over-hand mechanism of the kinesin stepping. Our theoretical predictions and numerical simulations include the off-axis displacements of the kinesin heads while the steps are performed. The results obtained are in a good agreement with recent experiments on the kinesin dynamics.

  6. Progress and perspective of the kinetochore-associated motor proteins

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The kinetochore is structurally composed of four layers. We know that three microtubule-based motor proteins such as CENP-E, dynein, and MCAK are located at the outmost region of the kinetochore. Experimentation of these motor functions betters our understanding of mitotic regulation, and chromosome movements in particular. With real-time studies of chromosome movements in live cells, we hope to illustrate the molecular mechanisms underlying mitotic regulation.

  7. Transport of organelles by elastically coupled motor proteins

    CERN Document Server

    Bhat, Deepak

    2014-01-01

    Motor-driven intracellular transport is a complex phenomenon where multiple motor proteins attached to a cargo are simultaneously engaged in pulling activity, often leading to tug-of-war and bidirectional motion. However, most mathematical and computational models ignore the details of the motor-cargo interaction. A few papers have studied more realistic models of cargo transport by including elastic motor-cargo coupling, but either restricts the number of motors and/or uses purely phenomenological forms for energy-dependent hopping rates. Here, we study a generic Model In which N motors are elastically coupled to a cargo, which itself is subject to thermal noise in the cytoplasm and an additional external applied force. The motor-hopping rates are chosen to satisfy detailed balance with respect to the energy of stretching. The master equation is converted to a linear Fokker-Planck equation (LFPE), which yields the average positions of the cargo and motors, as well as their fluctuations and correlation functi...

  8. Rab proteins specify motorized vesicle transport

    NARCIS (Netherlands)

    Wanschers, B.F.J.

    2008-01-01

    Small GTPases of the Rab-family are key regulators of intracellular membrane traffic. These proteins constantly cycle between an 'active' GTP-bound and 'inactive' GDP-bound state. In their GTP-bound conformation Rab proteins can engage in complex formation with so called effector proteins. It is at

  9. Run-and-tumble dynamics of cytoskeletal motor proteins

    CERN Document Server

    Hafner, Anne E; Rieger, Heiko; Shaebani, M Reza

    2016-01-01

    Cytoskeletal motor proteins are involved in major intracellular transport processes which are vital for maintaining appropriate cellular function. The motor exhibits distinct states of motility: active motion along filaments, and effectively stationary phase in which it detaches from the filaments and performs passive diffusion in the vicinity of the detachment point due to cytoplasmic crowding. The transition rates between motion and pause phases are asymmetric in general, and considerably affected by changes in environmental conditions which influences the efficiency of cargo delivery to specific targets. By considering the motion of molecular motor on a single filament as well as a dynamic filamentous network, we present an analytical model for the dynamics of self-propelled particles which undergo frequent pause phases. The interplay between motor processivity, structural properties of filamentous network, and transition rates between the two states of motility drastically changes the dynamics: multiple t...

  10. A simple theory of motor protein kinetics and energetics. II.

    Science.gov (United States)

    Qian, H

    2000-01-10

    A three-state stochastic model of motor protein [Qian, Biophys. Chem. 67 (1997) pp. 263-267] is further developed to illustrate the relationship between the external load on an individual motor protein in aqueous solution with various ATP concentrations and its steady-state velocity. A wide variety of dynamic motor behavior are obtained from this simple model. For the particular case of free-load translocation being the most unfavorable step within the hydrolysis cycle, the load-velocity curve is quasi-linear, V/Vmax = (cF/Fmax-c)/(1-c), in contrast to the hyperbolic relationship proposed by A.V. Hill for macroscopic muscle. Significant deviation from the linearity is expected when the velocity is less than 10% of its maximal (free-load) value--a situation under which the processivity of motor diminishes and experimental observations are less certain. We then investigate the dependence of load-velocity curve on ATP (ADP) concentration. It is shown that the free load Vmax exhibits a Michaelis-Menten like behavior, and the isometric Fmax increases linearly with ln([ATP]/[ADP]). However, the quasi-linear region is independent of the ATP concentration, yielding an apparently ATP-independent maximal force below the true isometric force. Finally, the heat production as a function of ATP concentration and external load are calculated. In simple terms and solved with elementary algebra, the present model provides an integrated picture of biochemical kinetics and mechanical energetics of motor proteins.

  11. Multiscale Polar Theory of Microtubule and 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 are building blocks of self-organized subcellular biological structures such as the mitotic spindle and the centrosomal microtubule array. These same ingredients can form new “bioactive” liquid-crystalline fluids that are intrinsically out of equilibrium and which display complex flows and defect dynamics. It is not yet well understood how microscopic activity, which involves polarity-dependent interactions between motor proteins and microtubules, yields such larger-scale dynamical structures. In our multiscale theory, Brownian dynamics simulations of polar microtubule ensembles driven by cross-linking motors allow us to study microscopic organization and stresses. Polarity sorting and cross-link relaxation emerge as two polar-specific sources of active destabilizing stress. On larger length scales, our continuum Doi-Onsager theory captures the hydrodynamic flows generated by polarity-dependent active stresses. The results connect local polar structure to flow structures and defect dynamics. PMID:25679909

  12. Membrane tube formation by motor proteins : forces and dynamics

    NARCIS (Netherlands)

    Koster, Gerbrand

    2005-01-01

    Membrane tubes are ubiquitous within cells. They have a diameter of approximately 50 nanometers, and are formed when a sufficiently large localized force is exerted on a membrane. Important generators of this force are the motor proteins that can move along cytoskeletal filaments. We studied

  13. Protein Synthesis Inhibition Blocks Consolidation of an Acrobatic Motor Skill

    Science.gov (United States)

    Kaelin-Lang, Alain; Dichgans, Johannes; Schulz, Jorg B.; Luft, Andreas R.; Buitrago, Manuel M.

    2004-01-01

    To investigate whether motor skill learning depends on de novo protein synthesis, adult rats were trained in an acrobatic locomotor task (accelerating rotarod) for 7 d. Animals were systemically injected with cycloheximide (CHX, 0.5 mg/kg, i.p.) 1 h before sessions 1 and 2 or sessions 2 and 3. Control rats received vehicle injections before…

  14. Role of adaptor proteins in motor regulation and membrane transport

    NARCIS (Netherlands)

    M.A. Schlager (Max)

    2010-01-01

    markdownabstract__Abstract__ Active transport along the cytoskeleton is a process essential for proper cellular function. Although much is known about the motor proteins that generate the necessary force and the cytoskeleton that provides the cellular infrastructure, many questions still remain. Fo

  15. Phenomenological analysis of ATP dependence of motor proteins.

    Directory of Open Access Journals (Sweden)

    Yunxin Zhang

    Full Text Available In this study, through phenomenological comparison of the velocity-force data of processive motor proteins, including conventional kinesin, cytoplasmic dynein and myosin V, I found that, the ratio between motor velocities of two different ATP concentrations is almost invariant for any substall, superstall or negative external loads. Therefore, the velocity of motors can be well approximated by a Michaelis-Menten like formula V = [ATP]k(FL([ATP] + K(M, with L the step size, and k(F the external load F dependent rate of one mechanochemical cycle of motor motion in saturated ATP solution. The difference of Michaelis-Menten constant K(M for substall, superstall and negative external load indicates, the configurations at which ATP molecule can bind to motor heads for these three cases might be different, though the expression of k(F as a function of F might be unchanged for any external load F. Verifications of this Michaelis-Menten like formula has also been done by fitting to the recent experimental data.

  16. Phenomenological analysis of ATP dependence of motor protein

    CERN Document Server

    Zhang, Yunxin

    2011-01-01

    In this study, through phenomenological comparison of the velocity-force data of processive motor proteins, including conventional kinesin, cytoplasmic dynein and myosin V, we found that, the ratio between motor velocities of two different ATP concentrations is almost invariant for any substall, superstall or negative external loads. Therefore, the velocity of motor can be well approximated by a Michaelis-Menten like formula $V=\\atp k(F)L/(\\atp +K_M)$, with $L$ the step size, and $k(F)$ the external load $F$ dependent rate of one mechanochemical cycle of motor motion in saturated ATP solution. The difference of Michaelis-Menten constant $K_M$ for substall, superstall and negative external load indicates, the ATP molecule affinity of motor head for these three cases are different, though the expression of $k(F)$ as a function of $F$ might be unchanged for any external load $F$. Verifications of this Michaelis-Menten like formula has also been done by fitting to the recent experimental data.

  17. How occasional backstepping can speed up a processive motor protein

    CERN Document Server

    Bier, M

    2008-01-01

    Fueled by the hydrolysis of ATP, the motor protein kinesin literally walks on two legs along the biopolymer microtubule. The number of accidental backsteps that kinesin takes appears to be much larger than what one would expect given the amount of free energy that ATP hydrolysis makes available. This is puzzling as more than a billion years of natural selection should have optimized the motor protein for its speed and efficiency. But more backstepping allows for the production of more entropy. Such entropy production will make free energy available. With this additional free energy, the catalytic cycle of the kinesin can be speeded up. We show how measured backstep percentages represent an optimum at which maximal net forward speed is achieved.

  18. Cargo transportation by two species of motor protein.

    Science.gov (United States)

    Zhang, Yunxin

    2013-05-01

    The cargo motion in living cells transported by two species of motor protein with different intrinsic directionalities is discussed in this study. Similarly to single motor movement, the cargo steps forward and backward along a microtubule stochastically. Recent experiments found that cargo transportation by two motor species has a memory; it does not change its direction as frequently as expected, which means that its forward and backward step rates depend on its previous motion trajectory. By assuming that the cargo has only the least possible memory, i.e., its step direction depends only on the direction of its last step, two cases of cargo motion are analyzed in detail in this study: (I) cargo motion under constant external load, and (II) cargo motion in one fixed optical trap. Due to the existence of memory, in the first case, the cargo can keep moving in the same direction for a long distance. In the second case, the cargo will oscillate in the trap. The oscillation period decreases and the oscillation amplitude increases with increasing forward step rate of the motor, but both of them decrease with increasing trap stiffness. The most likely location of the cargo, where the probability of finding the oscillating cargo is maximum, may be the same as or may be different from the trap center, which depends on the step rates of the two motor species. Meanwhile, if the motors are robust, i.e., their forward to backward step rate ratios are high, there may be two such most likely locations, located one on each side of the trap center. The probability of finding the cargo in a given location, the probability of the cargo being in forward or backward motion, and various mean first passage times of the cargo to a given location or a given state are also analyzed.

  19. Run-and-pause dynamics of cytoskeletal motor proteins

    Science.gov (United States)

    Hafner, Anne E.; Santen, Ludger; Rieger, Heiko; Shaebani, M. Reza

    2016-11-01

    Cytoskeletal motor proteins are involved in major intracellular transport processes which are vital for maintaining appropriate cellular function. When attached to cytoskeletal filaments, the motor exhibits distinct states of motility: active motion along the filaments, and pause phase in which it remains stationary for a finite time interval. The transition probabilities between motion and pause phases are asymmetric in general, and considerably affected by changes in environmental conditions which influences the efficiency of cargo delivery to specific targets. By considering the motion of individual non-interacting molecular motors on a single filament as well as a dynamic filamentous network, we present an analytical model for the dynamics of self-propelled particles which undergo frequent pause phases. The interplay between motor processivity, structural properties of filamentous network, and transition probabilities between the two states of motility drastically changes the dynamics: multiple transitions between different types of anomalous diffusive dynamics occur and the crossover time to the asymptotic diffusive or ballistic motion varies by several orders of magnitude. We map out the phase diagrams in the space of transition probabilities, and address the role of initial conditions of motion on the resulting dynamics.

  20. Cargo transportation by two species of motor protein

    CERN Document Server

    Zhang, Yunxin

    2012-01-01

    The cargo motion in living cells transported by two species of motor protein with different intrinsic directionality is discussed in this study. Similar to single motor movement, cargo steps forward and backward along microtubule stochastically. Recent experiments found that, cargo transportation by two motor species has a memory, it does not change its direction as frequently as expected, which means that its forward and backward step rates depends on its previous motion trajectory. By assuming cargo has only the least memory, i.e. its step direction depends only on the direction of its last step, two cases of cargo motion are detailed analyzed in this study: {\\bf (I)} cargo motion under constant external load; and {\\bf (II)} cargo motion in one fixed optical trap. Due to the existence of memory, for the first case, cargo can keep moving in the same direction for a long distance. For the second case, the cargo will oscillate in the trap. The oscillation period decreases and the oscillation amplitude increase...

  1. From electron microscopy to molecular cell biology, molecular genetics and structural biology: intracellular transport and kinesin superfamily proteins, KIFs: genes, structure, dynamics and functions.

    Science.gov (United States)

    Hirokawa, Nobutaka

    2011-01-01

    Cells transport and sort various proteins and lipids following synthesis as distinct types of membranous organelles and protein complexes to the correct destination at appropriate velocities. This intracellular transport is fundamental for cell morphogenesis, survival and functioning not only in highly polarized neurons but also in all types of cells in general. By developing quick-freeze electron microscopy (EM), new filamentous structures associated with cytoskeletons are uncovered. The characterization of chemical structures and functions of these new filamentous structures led us to discover kinesin superfamily molecular motors, KIFs. In this review, I discuss the identification of these new structures and characterization of their functions using molecular cell biology and molecular genetics. KIFs not only play significant roles by transporting various cargoes along microtubule rails, but also play unexpected fundamental roles on various important physiological processes such as learning and memory, brain wiring, development of central nervous system and peripheral nervous system, activity-dependent neuronal survival, development of early embryo, left-right determination of our body and tumourigenesis. Furthermore, by combining single-molecule biophysics with structural biology such as cryo-electrom microscopy and X-ray crystallography, atomic structures of KIF1A motor protein of almost all states during ATP hydrolysis have been determined and a common mechanism of motility has been proposed. Thus, this type of studies could be a good example of really integrative multidisciplinary life science in the twenty-first century.

  2. Collective effects in intra-cellular molecular motor transport: coordination, cooperation and competetion

    CERN Document Server

    Chowdhury, D

    2006-01-01

    Molecular motors do not work in isolation {\\it in-vivo}. We highlight some of the coordinations, cooperations and competitions that determine the collective properties of molecular motors in eukaryotic cells. In the context of traffic-like movement of motors on a track, we emphasize the importance of single-motor bio-chemical cycle and enzymatic activity on their collective spatio-temporal organisation. Our modelling strategy is based on a synthesis- the same model describes the single-motor mechano-chemistry at sufficiently low densities whereas at higher densities it accounts for the collective flow properties and the density profiles of the motors. We consider two specific examples, namely, traffic of single-headed kinesin motors KIF1A on a microtubule track and ribosome traffic on a messenger RNA track.

  3. Integrated regulation of motor-driven organelle transport by scaffolding proteins.

    Science.gov (United States)

    Fu, Meng-meng; Holzbaur, Erika L F

    2014-10-01

    Intracellular trafficking pathways, including endocytosis, autophagy, and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs (trafficking kinesin-binding protein), JIP1, JIP3 (JNK-interacting proteins), huntingtin, and Hook1, interact with molecular motors to coordinate activity and sustain unidirectional transport. Scaffolding proteins also bind to upstream regulatory proteins, including kinases and GTPases, to modulate transport in the cell. This integration of regulatory control with motor activity allows for cargo-specific changes in the transport or targeting of organelles in response to cues from the complex cellular environment.

  4. Intermolecular forces between the motor protein and the filament.

    Science.gov (United States)

    Suda, H; Taylor, T W

    1993-03-07

    Intermolecular forces between motor proteins and filaments were evaluated on the basis of the experimental data of an in vitro motility assay by considering the molecular friction in the movement system. The molecular friction was caused by a different mechanism from that of the hydrodynamic drag. However, the molecular frictional forces apparently gave the same expression as the hydrodynamic frictional forces. The resulting equation was very effective in examining the physical properties of the weak interaction in the dynein-microtubules system from basic experiments carried out by Vale et al. (1989). From careful analysis of their experimental data, it was concluded that the hydrodynamic friction was not dominant, even in the weak binding state. The electrostatic interaction between dynein-heads and microtubules in the weak binding state was analyzed by applying the DLVO (Derjaguin-Landau-Verway-Overbeek) theory in colloid science through the ionic dependence of one-dimensional diffusion. The interacting distance between charges which took part in the weak adhesion was estimated to be 3 nm. In the present study, the molecular mechanism of the sliding velocity was also investigated for the myosin-actin filaments and the kinesin-microtubules systems by fitting the ATP-dependence and the ionic dependence in ATP-driven active sliding.

  5. Life without double-headed non-muscle myosin II motor proteins

    Directory of Open Access Journals (Sweden)

    Venkaiah eBetapudi

    2014-07-01

    Full Text Available Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

  6. Life without double-headed non-muscle myosin II motor proteins

    Science.gov (United States)

    Betapudi, Venkaiah

    2014-07-01

    Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

  7. Protein expression of sensory and motor nerves: Two-dimensional gel electrophoresis and mass spectrometry.

    Science.gov (United States)

    Ren, Zhiwu; Wang, Yu; Peng, Jiang; Zhang, Li; Xu, Wenjing; Liang, Xiangdang; Zhao, Qing; Lu, Shibi

    2012-02-15

    The present study utilized samples from bilateral motor branches of the femoral nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal cord, to detect differential protein expression using two-dimensional gel electrophoresis and nano ultra-high performance liquid chromatography electrospray ionization mass spectrometry tandem mass spectrometry techniques. A mass spectrum was identified using the Mascot search. Results revealed differential expression of 11 proteins, including transgelin, Ig kappa chain precursor, plasma glutathione peroxidase precursor, an unnamed protein product (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein, lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and sensory nerves. Results suggested that these proteins played roles in specific nerve regeneration following peripheral nerve injury and served as specific markers for motor and sensory nerves.

  8. Protein expression of sensory and motor nerves Two-dimensional gel electrophoresis and mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Zhiwu Ren; Yu Wang; Jiang Peng; Li Zhang; Wenjing Xu; Xiangdang Liang; Qing Zhao; Shibi Lu

    2012-01-01

    The present study utilized samples from bilateral motor branches of the femoral nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal cord, to detect differential protein expression using two-dimensional gel electrophoresis and nano ultra-high performance liquid chromatography electrospray ionization mass spectrometry tandem mass spectrometry techniques. A mass spectrum was identified using the Mascot search. Results revealed differential expression of 11 proteins, including transgelin, Ig kappa chain precursor, plasma glutathione peroxidase precursor, an unnamed protein product (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein, lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and sensory nerves. Results suggested that these proteins played roles in specific nerve regeneration following peripheral nerve injury and served as specific markers for motor and sensory nerves.

  9. Motor fluctuations due to interaction between dietary protein and levodopa in Parkinson’s disease

    OpenAIRE

    Virmani, Tuhin; Tazan, Sirinan; Mazzoni, Pietro; Ford, Blair; Greene, Paul E.

    2016-01-01

    Background The modulation of levodopa transport across the blood brain barrier by large neutral amino acids is well documented. Protein limitation and protein redistribution diets may improve motor fluctuations in patients with Parkinson’s disease but the pharmacokinetics and pharmacodynamics of levodopa and amino acids are highly variable. Methods Clinical records of 1037 Parkinson’s disease patients were analyzed to determine the proportion of patients with motor fluctuations related to pro...

  10. Stochastic Resonance of Single (Independent of Each Other) Protein Motor System with Fluctuating Potential Barrier

    Institute of Scientific and Technical Information of China (English)

    MA Song-Hua; LI Jing-Hui; JIANG Yong-Qing; FANG Jian-Ping

    2008-01-01

    A single (independent of each other) protein motor system with fluctuating potential barrier and subject to sine electric field is investigated. We first derive the approximate Langevin equation of this system with fluctuating potential barrier. Then from this approximate Langevin equation, we calculate the signal-to-noise ratio (SNR) in the adiabatic limit. The phenomenon of stochastic resonance is found for this protein motor system with fluctuating potential barrier.

  11. Spiral Defects in Motility Assays: A Measure of Motor Protein Force

    Science.gov (United States)

    Bourdieu, L.; Duke, T.; Elowitz, M. B.; Winkelmann, D. A.; Leibler, S.; Libchaber, A.

    1995-07-01

    In a commonly used motility assay, cytoskeletal filaments are observed as they glide over a surface coated with motor proteins. Defects in the motion frequently interrupt the flow of filaments. Examination of one such defect, in which a filament adopts a spiral form and rotates about a fixed point, provides a simple measure of the force exerted by the motor proteins. We demonstrate the universality of this approach by estimating the elementary forces of both myosin and kinesin.

  12. Comparative proteomic analysis of differentially expressed proteins between peripheral sensory and motor nerves.

    Science.gov (United States)

    He, Qianru; Man, Lili; Ji, Yuhua; Zhang, Shuqiang; Jiang, Maorong; Ding, Fei; Gu, Xiaosong

    2012-06-01

    Peripheral sensory and motor nerves have different functions and different approaches to regeneration, especially their distinct ability to accurately reinervate terminal nerve pathways. To understand the molecular aspects underlying these differences, the proteomics technique by coupling isobaric tags for relative and absolute quantitation (iTRAQ) with online two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) was used to investigate the protein profile of sensory and motor nerve samples from rats. A total of 1472 proteins were identified in either sensory or motor nerve. Of them, 100 proteins showed differential expressions between both nerves, and some of them were validated by quantitative real time RT-PCR, Western blot analysis, and immunohistochemistry. In the light of functional categorization, the differentially expressed proteins in sensory and motor nerves, belonging to a broad range of classes, were related to a diverse array of biological functions, which included cell adhesion, cytoskeleton, neuronal plasticity, neurotrophic activity, calcium-binding, signal transduction, transport, enzyme catalysis, lipid metabolism, DNA-binding, synaptosome function, actin-binding, ATP-binding, extracellular matrix, and commitment to other lineages. The relatively higher expressed proteins in either sensory or motor nerve were tentatively discussed in combination with their specific molecular characteristics. It is anticipated that the database generated in this study will provide a solid foundation for further comprehensive investigation of functional differences between sensory and motor nerves, including the specificity of their regeneration.

  13. TRIM3 regulates the motility of the kinesin motor protein KIF21B.

    Directory of Open Access Journals (Sweden)

    Dorthe Labonté

    Full Text Available Kinesin superfamily proteins (KIFs are molecular motors that transport cellular cargo along the microtubule cytoskeleton. KIF21B is a neuronal kinesin that is highly enriched in dendrites. The regulation and specificity of microtubule transport involves the binding of motors to individual cargo adapters and accessory proteins. Moreover, posttranslational modifications of either the motor protein, their cargos or tubulin regulate motility, cargo recognition and the binding or unloading of cargos. Here we show that the ubiquitin E3 ligase TRIM3, also known as BERP, interacts with KIF21B via its RBCC domain. TRIM3 is found at intracellular and Golgi-derived vesicles and co-localizes with the KIF21B motor in neurons. Trim3 gene deletion in mice and TRIM3 overexpression in cultured neurons both suggested that the E3-ligase function of TRIM3 is not involved in KIF21B degradation, however TRIM3 depletion reduces the motility of the motor. Together, our data suggest that TRIM3 is a regulator in the modulation of KIF21B motor function.

  14. Sub-angstrom single-molecule measurements of motor proteins using a nanopore

    Science.gov (United States)

    Derrington, Ian M; Craig, Jonathan M; Stava, Eric; Laszlo, Andrew H; Ross, Brian C; Brinkerhoff, Henry; Nova, Ian C; Doering, Kenji; Tickman, Benjamin I; Ronaghi, Mostafa; Mandell, Jeffrey G; Gunderson, Kevin L; Gundlach, Jens H

    2016-01-01

    Present techniques for measuring the motion of single motor proteins, such as FRET and optical tweezers, are limited to a resolution of ~300 pm. We use ion current modulation through the protein nanopore MspA to observe translocation of helicase Hel308 on DNA with up to ~40 picometer sensitivity. This approach should be applicable to any protein that translocates on DNA or RNA, including helicases, polymerases, recombinases and DNA repair enzymes. PMID:26414351

  15. Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila

    OpenAIRE

    Stuart J Grice; Ji-Long Liu

    2011-01-01

    Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death. It is currently unknown how the reduction of this ubiquitously essential protein can lead to tissue-specific abnormalities. In addition, it is still not known whether the disease is caused by developmental or degenerative defe...

  16. Specific transport of target molecules by motor proteins in microfluidic channels.

    Science.gov (United States)

    Tarhan, Mehmet C; Yokokawa, Ryuji; Morin, Fabrice O; Fujita, Hiroyuki

    2013-06-03

    Direct transport powered by motor proteins can alleviate the challenges presented by miniaturization of microfluidic systems. There have been several recent attempts to build motor-protein-driven transport systems based on simple capturing or transport mechanisms. However, to achieve a multifunctional device for practical applications, a more complex sorting/transport system should be realized. Herein, the proof of concept of a sorting device employing selective capture of distinct target molecules and transport of the sorted molecules to different predefined directions is presented. By combining the bottom-up functionality of biological systems with the top-down handling capabilities of micro-electromechanical systems technology, highly selective molecular recognition and motor-protein-based transport is integrated in a microfluidic channel network.

  17. Structure-based molecular simulations reveal the enhancement of biased Brownian motions in single-headed kinesin.

    Directory of Open Access Journals (Sweden)

    Ryo Kanada

    Full Text Available Kinesin is a family of molecular motors that move unidirectionally along microtubules (MT using ATP hydrolysis free energy. In the family, the conventional two-headed kinesin was experimentally characterized to move unidirectionally through "walking" in a hand-over-hand fashion by coordinated motions of the two heads. Interestingly a single-headed kinesin, a truncated KIF1A, still can generate a biased Brownian movement along MT, as observed by in vitro single molecule experiments. Thus, KIF1A must use a different mechanism from the conventional kinesin to achieve the unidirectional motions. Based on the energy landscape view of proteins, for the first time, we conducted a set of molecular simulations of the truncated KIF1A movements over an ATP hydrolysis cycle and found a mechanism exhibiting and enhancing stochastic forward-biased movements in a similar way to those in experiments. First, simulating stand-alone KIF1A, we did not find any biased movements, while we found that KIF1A with a large friction cargo-analog attached to the C-terminus can generate clearly biased Brownian movements upon an ATP hydrolysis cycle. The linked cargo-analog enhanced the detachment of the KIF1A from MT. Once detached, diffusion of the KIF1A head was restricted around the large cargo which was located in front of the head at the time of detachment, thus generating a forward bias of the diffusion. The cargo plays the role of a diffusional anchor, or cane, in KIF1A "walking."

  18. Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS.

    Science.gov (United States)

    Ciryam, Prajwal; Lambert-Smith, Isabella A; Bean, Daniel M; Freer, Rosie; Cid, Fernando; Tartaglia, Gian Gaetano; Saunders, Darren N; Wilson, Mark R; Oliver, Stephen G; Morimoto, Richard I; Dobson, Christopher M; Vendruscolo, Michele; Favrin, Giorgio; Yerbury, Justin J

    2017-05-16

    Amyotrophic lateral sclerosis (ALS) is a heterogeneous degenerative motor neuron disease linked to numerous genetic mutations in apparently unrelated proteins. These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and form a variety of intracellular inclusion bodies that are characteristic of different neuropathological subtypes of the disease. Contained within these inclusions are a variety of proteins that do not share obvious characteristics other than coaggregation. However, recent evidence from other neurodegenerative disorders suggests that disease-affected biochemical pathways can be characterized by the presence of proteins that are supersaturated, with cellular concentrations significantly greater than their solubilities. Here, we show that the proteins that form inclusions of mutant SOD1, TDP-43, and FUS are not merely a subset of the native interaction partners of these three proteins, which are themselves supersaturated. To explain the presence of coaggregating proteins in inclusions in the brain and spinal cord, we observe that they have an average supersaturation even greater than the average supersaturation of the native interaction partners in motor neurons, but not when scores are generated from an average of other human tissues. These results suggest that inclusion bodies in various forms of ALS result from a set of proteins that are metastable in motor neurons, and thus prone to aggregation upon a disease-related progressive collapse of protein homeostasis in this specific setting.

  19. Stall force of a cargo driven by N interacting motor proteins

    Science.gov (United States)

    Bhat, Deepak; Gopalakrishnan, Manoj

    2017-01-01

    We study a generic one-dimensional model for an intracellular cargo driven by N motor proteins against an external applied force. The model includes motor-cargo and motor-motor interactions. The cargo motion is described by an over-damped Langevin equation, while motor dynamics is specified by hopping rates which follow a local detailed balance condition with respect to the change in energy per hopping event. Based on this model, we show that the stall force, the mean external force corresponding to zero mean cargo velocity, is completely independent of the details of the interactions and is, therefore, always equal to the sum of the stall forces of the individual motors. This exact result is arrived on the basis of a simple assumption: the (macroscopic) state of stall of the cargo is analogous to a state of thermodynamic equilibrium, and is characterized by vanishing net probability current between any two microstates, with the latter specified by motor positions relative to the cargo. The corresponding probability distribution of the microstates under stall is also determined. These predictions are in complete agreement with numerical simulations, carried out using specific forms of interaction potentials.

  20. Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Luxi Wang

    2017-06-01

    Full Text Available Levodopa is considered to be the most effective symptomatic drug for Parkinson's disease (PD. As the disease progresses, however, the patients are likely to experience a reduced response to levodopa and develop motor fluctuations (i.e., end-of-dose wearing off and unpredictable “on-off”. Protein-rich diets and elevated plasma concentrations of large neutral amino acids have been proved to impair the therapeutic effect of levodopa by reducing its absorption and influx into the brain. On the other hand, the protein-restricted diets including low-protein diet (LPD, protein-redistribution diet (PRD and PRD with use of low-protein products can all improve the efficacy of levodopa in patients with motor fluctuations. However, it should be noted that protein-restricted diets may also contribute to several side effects, including dyskinesia, weight loss, and malnutrition (e.g., protein and calcium insufficiency. Together, protein-restricted diets are an effective approach to improve motor fluctuations in PD patients, while long-term adherence to these diets requires monitoring for side effects.

  1. Versatile microsphere attachment of GFP-labeled motors and other tagged proteins with preserved functionality

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    Michael Bugiel

    2015-11-01

    Full Text Available Microspheres are often used as handles for protein purification or force spectroscopy. For example, optical tweezers apply forces on trapped particles to which motor proteins are attached. However, even though many attachment strategies exist, procedures are often limited to a particular biomolecule and prone to non-specific protein or surface attachment. Such interactions may lead to loss of protein functionality or microsphere clustering. Here, we describe a versatile coupling procedure for GFP-tagged proteins via a polyethylene glycol linker preserving the functionality of the coupled proteins. The procedure combines well-established protocols, is highly reproducible, reliable, and can be used for a large variety of proteins. The coupling is efficient and can be tuned to the desired microsphere-to-protein ratio. Moreover, microspheres hardly cluster or adhere to surfaces. Furthermore, the procedure can be adapted to different tags providing flexibility and a promising attachment strategy for any tagged protein.

  2. Pfarao: a web application for protein family analysis customized for cytoskeletal and motor proteins (CyMoBase

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    Kollmar Martin

    2006-11-01

    Full Text Available Abstract Background Annotation of protein sequences of eukaryotic organisms is crucial for the understanding of their function in the cell. Manual annotation is still by far the most accurate way to correctly predict genes. The classification of protein sequences, their phylogenetic relation and the assignment of function involves information from various sources. This often leads to a collection of heterogeneous data, which is hard to track. Cytoskeletal and motor proteins consist of large and diverse superfamilies comprising up to several dozen members per organism. Up to date there is no integrated tool available to assist in the manual large-scale comparative genomic analysis of protein families. Description Pfarao (Protein Family Application for Retrieval, Analysis and Organisation is a database driven online working environment for the analysis of manually annotated protein sequences and their relationship. Currently, the system can store and interrelate a wide range of information about protein sequences, species, phylogenetic relations and sequencing projects as well as links to literature and domain predictions. Sequences can be imported from multiple sequence alignments that are generated during the annotation process. A web interface allows to conveniently browse the database and to compile tabular and graphical summaries of its content. Conclusion We implemented a protein sequence-centric web application to store, organize, interrelate, and present heterogeneous data that is generated in manual genome annotation and comparative genomics. The application has been developed for the analysis of cytoskeletal and motor proteins (CyMoBase but can easily be adapted for any protein.

  3. GPR55, a G-protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination.

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    Chia-Shan Wu

    Full Text Available The G-protein coupled receptor 55 (GPR55 is activated by lysophosphatidylinositols and some cannabinoids. Recent studies found prominent roles for GPR55 in neuropathic/inflammatory pain, cancer and bone physiology. However, little is known about the role of GPR55 in CNS development and function. To address this question, we performed a detailed characterization of GPR55 knockout mice using molecular, anatomical, electrophysiological, and behavioral assays. Quantitative PCR studies found that GPR55 mRNA was expressed (in order of decreasing abundance in the striatum, hippocampus, forebrain, cortex, and cerebellum. GPR55 deficiency did not affect the concentrations of endocannabinoids and related lipids or mRNA levels for several components of the endocannabinoid system in the hippocampus. Normal synaptic transmission and short-term as well as long-term synaptic plasticity were found in GPR55 knockout CA1 pyramidal neurons. Deleting GPR55 function did not affect behavioral assays assessing muscle strength, gross motor skills, sensory-motor integration, motor learning, anxiety or depressive behaviors. In addition, GPR55 null mutant mice exhibited normal contextual and auditory-cue conditioned fear learning and memory in a Pavlovian conditioned fear test. In contrast, when presented with tasks requiring more challenging motor responses, GPR55 knockout mice showed impaired movement coordination. Taken together, these results suggest that GPR55 plays a role in motor coordination, but does not strongly regulate CNS development, gross motor movement or several types of learned behavior.

  4. GPR55, a G-protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination.

    Science.gov (United States)

    Wu, Chia-Shan; Chen, Hongmei; Sun, Hao; Zhu, Jie; Jew, Chris P; Wager-Miller, James; Straiker, Alex; Spencer, Corinne; Bradshaw, Heather; Mackie, Ken; Lu, Hui-Chen

    2013-01-01

    The G-protein coupled receptor 55 (GPR55) is activated by lysophosphatidylinositols and some cannabinoids. Recent studies found prominent roles for GPR55 in neuropathic/inflammatory pain, cancer and bone physiology. However, little is known about the role of GPR55 in CNS development and function. To address this question, we performed a detailed characterization of GPR55 knockout mice using molecular, anatomical, electrophysiological, and behavioral assays. Quantitative PCR studies found that GPR55 mRNA was expressed (in order of decreasing abundance) in the striatum, hippocampus, forebrain, cortex, and cerebellum. GPR55 deficiency did not affect the concentrations of endocannabinoids and related lipids or mRNA levels for several components of the endocannabinoid system in the hippocampus. Normal synaptic transmission and short-term as well as long-term synaptic plasticity were found in GPR55 knockout CA1 pyramidal neurons. Deleting GPR55 function did not affect behavioral assays assessing muscle strength, gross motor skills, sensory-motor integration, motor learning, anxiety or depressive behaviors. In addition, GPR55 null mutant mice exhibited normal contextual and auditory-cue conditioned fear learning and memory in a Pavlovian conditioned fear test. In contrast, when presented with tasks requiring more challenging motor responses, GPR55 knockout mice showed impaired movement coordination. Taken together, these results suggest that GPR55 plays a role in motor coordination, but does not strongly regulate CNS development, gross motor movement or several types of learned behavior.

  5. Kermit interacts with Gαo, Vang, and motor proteins in Drosophila planar cell polarity.

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    Chen Lin

    Full Text Available In addition to the ubiquitous apical-basal polarity, epithelial cells are often polarized within the plane of the tissue--the phenomenon known as planar cell polarity (PCP. In Drosophila, manifestations of PCP are visible in the eye, wing, and cuticle. Several components of the PCP signaling have been characterized in flies and vertebrates, including the heterotrimeric Go protein. However, Go signaling partners in PCP remain largely unknown. Using a genetic screen we uncover Kermit, previously implicated in G protein and PCP signaling, as a novel binding partner of Go. Through pull-down and genetic interaction studies, we find that Kermit interacts with Go and another PCP component Vang, known to undergo intracellular relocalization during PCP establishment. We further demonstrate that the activity of Kermit in PCP differentially relies on the motor proteins: the microtubule-based dynein and kinesin motors and the actin-based myosin VI. Our results place Kermit as a potential transducer of Go, linking Vang with motor proteins for its delivery to dedicated cellular compartments during PCP establishment.

  6. Low-protein and protein-redistribution diets for Parkinson's disease patients with motor fluctuations: a systematic review.

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    Cereda, Emanuele; Barichella, Michela; Pedrolli, Carlo; Pezzoli, Gianni

    2010-10-15

    The American Academy of Neurology suggests advising the redistribution of daily protein meal content to every Parkinson's disease (PD) patient with motor fluctuations during levodopa treatment. However, no comprehensive evaluation of this complementary therapy has been performed. A systematic review of intervention studies investigating the neurologic outcome of low-protein (nutritional status should be evaluated and true effectiveness in clinical practice should be reassessed, given the changes in levodopa formulations and the introduction of several adjuvants (levodopa degradation inhibitors and/or dopamine agonists).

  7. The influence of protein kinases and microtubule binding proteins on cerebellar motor learning

    NARCIS (Netherlands)

    F.J. Branco Madeira

    2007-01-01

    textabstractThe cerebellum (from the latin - little brain) is located at the posterior end of the brain. It is known to be involved in vital functions like the control of heart beat and respiration and also in motor coordination, a function involving balance and equilibrium, which also requires the

  8. Reconstructing the phylogeny of 21 completely sequenced arthropod species based on their motor proteins

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    Kollmar Martin

    2009-04-01

    Full Text Available Abstract Background Motor proteins have extensively been studied in the past and consist of large superfamilies. They are involved in diverse processes like cell division, cellular transport, neuronal transport processes, or muscle contraction, to name a few. Vertebrates contain up to 60 myosins and about the same number of kinesins that are spread over more than a dozen distinct classes. Results Here, we present the comparative genomic analysis of the motor protein repertoire of 21 completely sequenced arthropod species using the owl limpet Lottia gigantea as outgroup. Arthropods contain up to 17 myosins grouped into 13 classes. The myosins are in almost all cases clear paralogs, and thus the evolution of the arthropod myosin inventory is mainly determined by gene losses. Arthropod species contain up to 29 kinesins spread over 13 classes. In contrast to the myosins, the evolution of the arthropod kinesin inventory is not only determined by gene losses but also by many subtaxon-specific and species-specific gene duplications. All arthropods contain each of the subunits of the cytoplasmic dynein/dynactin complex. Except for the dynein light chains and the p150 dynactin subunit they contain single gene copies of the other subunits. Especially the roadblock light chain repertoire is very species-specific. Conclusion All 21 completely sequenced arthropods, including the twelve sequenced Drosophila species, contain a species-specific set of motor proteins. The phylogenetic analysis of all genes as well as the protein repertoire placed Daphnia pulex closest to the root of the Arthropoda. The louse Pediculus humanus corporis is the closest relative to Daphnia followed by the group of the honeybee Apis mellifera and the jewel wasp Nasonia vitripennis. After this group the rust-red flour beetle Tribolium castaneum and the silkworm Bombyx mori diverged very closely from the lineage leading to the Drosophila species.

  9. [Influence of protein-restricted diet on motor response fluctuations in Parkinson's disease].

    Science.gov (United States)

    Hirata, H; Asanuma, M; Kondo, Y; Ogawa, N

    1992-09-01

    The clinical management of Parkinson's disease has been revolutionized by the introduction of levodopa therapy. It has significantly reduced disability and has extended life expectancies of patients with Parkinson's disease. However, motor response fluctuations frequently appear in patients after long-term treatment with levodopa. In this study, we investigated the effect of protein-restricted diet on fluctuations in eight patients with Parkinson's disease who had been receiving long-term levodopa treatment (mean 12.5 years). Two weeks of protein-restricted daytime diet (7.5 g total at breakfast and lunch) was followed by 12.5 g total at breakfast and lunch. At night, high-protein diet (40-50 g at dinner) was offered to the patients in order to maintain total daily protein intake at Japanese standard level. The medication schedule of levodopa and other antiparkinsonian drugs was not changed within 2 weeks after the study was began. Fluctuations were reduced in 7 of the 8 patients. But in only one patient (case 6), dyskinesia and general condition got worse and stopped this therapy. Body weight, serum protein and albumin levels did not change significantly for at least three month after the study was begun in every 6 patients who were examined. Homovanillic acid level of cerebrospinal fluid reduced in every 4 patients who were examined. We concluded that protein-restricted diet during the daytime offers a fascinating technique for the control of motor response fluctuations in patients with Parkinson's disease undergoing long-term levodopa treatment. But this therapy must be indicated carefully. Mechanism of this therapy may has something to do with improvement of dopamine metabolism in the brain.

  10. The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

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    Paul G. Donlin-Asp

    2017-02-01

    Full Text Available Spinal muscular atrophy (SMA is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs. SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3′ UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP complexes that associate with the cytoskeleton to facilitate trafficking. We have identified defects in mRNP assembly in cells and tissues from SMA disease models and patients that depend on the SMN Tudor domain and explain the observed deficiency in mRNA localization and local translation, providing insight into SMA pathogenesis as a ribonucleoprotein (RNP-assembly disorder.

  11. Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Delorme, Caroline; Joshi, Monika [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada); Allingham, John S., E-mail: allinghj@queensu.ca [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. Black-Right-Pointing-Pointer The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. Black-Right-Pointing-Pointer The MBP-Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the 'ATP state' of the mechanochemical cycle. This site differs from the Kar3 neck-core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

  12. Translocation of double-stranded DNA through membrane-adapted phi29 motor protein nanopores

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    Wendell, David; Jing, Peng; Geng, Jia; Subramaniam, Varuni; Lee, Tae Jin; Montemagno, Carlo; Guo, Peixuan

    2009-11-01

    Biological pores have been used to study the transport of DNA and other molecules, but most pores have channels that allow only the movement of small molecules and single-stranded DNA and RNA. The bacteriophage phi29 DNA-packaging motor, which allows double-stranded DNA to enter the virus during maturation and exit during an infection, contains a connector protein with a channel that is between 3.6 and 6 nm wide. Here we show that a modified version of this connector protein, when reconstituted into liposomes and inserted into planar lipid bilayers, allows the translocation of double-stranded DNA. The measured conductance of a single connector channel was 4.8 nS in 1 M KCl. This engineered and membrane-adapted phage connector is expected to have applications in microelectromechanical sensing, microreactors, gene delivery, drug loading and DNA sequencing.

  13. Survival Motor Neuron (SMN) protein is required for normal mouse liver development

    Science.gov (United States)

    Szunyogova, Eva; Zhou, Haiyan; Maxwell, Gillian K.; Powis, Rachael A.; Francesco, Muntoni; Gillingwater, Thomas H.; Parson, Simon H.

    2016-01-01

    Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is associated with a range of systemic pathologies reported in severe patients. Despite high levels of SMN protein in normal liver, there is no comprehensive study of liver pathology in SMA. We describe failed liver development in response to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red, small and has: iron deposition; immature sinusoids congested with blood; persistent erythropoietic elements and increased immature red blood cells; increased and persistent megakaryocytes which release high levels of platelets found as clot-like accumulations in the heart. Myelopoiesis in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings. Antisense treatment from birth with PMO25, increased lifespan and ameliorated all morphological defects in liver by postnatal day 21. Defects in the liver are evident at birth, prior to motor system pathology, and impair essential liver function in SMA. Liver is a key recipient of SMA therapies, and systemically delivered antisense treatment, completely rescued liver pathology. Liver therefore, represents an important therapeutic target in SMA. PMID:27698380

  14. Loss of RAD-23 Protects Against Models of Motor Neuron Disease by Enhancing Mutant Protein Clearance.

    Science.gov (United States)

    Jablonski, Angela M; Lamitina, Todd; Liachko, Nicole F; Sabatella, Mariangela; Lu, Jiayin; Zhang, Lei; Ostrow, Lyle W; Gupta, Preetika; Wu, Chia-Yen; Doshi, Shachee; Mojsilovic-Petrovic, Jelena; Lans, Hannes; Wang, Jiou; Kraemer, Brian; Kalb, Robert G

    2015-10-21

    Misfolded proteins accumulate and aggregate in neurodegenerative disease. The existence of these deposits reflects a derangement in the protein homeostasis machinery. Using a candidate gene screen, we report that loss of RAD-23 protects against the toxicity of proteins known to aggregate in amyotrophic lateral sclerosis. Loss of RAD-23 suppresses the locomotor deficit of Caenorhabditis elegans engineered to express mutTDP-43 or mutSOD1 and also protects against aging and proteotoxic insults. Knockdown of RAD-23 is further neuroprotective against the toxicity of SOD1 and TDP-43 expression in mammalian neurons. Biochemical investigation indicates that RAD-23 modifies mutTDP-43 and mutSOD1 abundance, solubility, and turnover in association with altering the ubiquitination status of these substrates. In human amyotrophic lateral sclerosis spinal cord, we find that RAD-23 abundance is increased and RAD-23 is mislocalized within motor neurons. We propose a novel pathophysiological function for RAD-23 in the stabilization of mutated proteins that cause neurodegeneration. In this work, we identify RAD-23, a component of the protein homeostasis network and nucleotide excision repair pathway, as a modifier of the toxicity of two disease-causing, misfolding-prone proteins, SOD1 and TDP-43. Reducing the abundance of RAD-23 accelerates the degradation of mutant SOD1 and TDP-43 and reduces the cellular content of the toxic species. The existence of endogenous proteins that act as "anti-chaperones" uncovers new and general targets for therapeutic intervention. Copyright © 2015 the authors 0270-6474/15/3514286-21$15.00/0.

  15. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons

    DEFF Research Database (Denmark)

    Alvarez Herrero, Susana; Pinchenko, Volodymyr; Klein, Dennis

    2011-01-01

    by pharmacologic block using the subtype-selective Na(V)1.8 blocker A-803467 and chronically in Na(V)1.8 knock-outs. We found that in the context of dysmyelination, abnormal potassium ion currents and membrane depolarization, the ectopic Na(V)1.8 channels further impair the motor axon excitability in protein zero...... and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage gated sodium channel isoform, which...... is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold tracking' excitability studies...

  16. Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in Parkinson Disease.

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    Atsushi Umemura

    Full Text Available C-reactive protein (CRP, a blood inflammatory biomarker, is associated with the development of Alzheimer disease. In animal models of Parkinson disease (PD, systemic inflammatory stimuli can promote neuroinflammation and accelerate dopaminergic neurodegeneration. However, the association between long-term systemic inflammations and neurodegeneration has not been assessed in PD patients.To investigate the longitudinal effects of baseline CRP concentrations on motor prognosis in PD.Retrospective analysis of 375 patients (mean age, 69.3 years; mean PD duration, 6.6 years. Plasma concentrations of high-sensitivity CRP were measured in the absence of infections, and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III scores were measured at five follow-up intervals (Days 1-90, 91-270, 271-450, 451-630, and 631-900.Change of UPDRS-III scores from baseline to each of the five follow-up periods.Change in UPDRS-III scores was significantly greater in PD patients with CRP concentrations ≥0.7 mg/L than in those with CRP concentrations <0.7 mg/L, as determined by a generalized estimation equation model (P = 0.021 for the entire follow-up period and by a generalized regression model (P = 0.030 for the last follow-up interval (Days 631-900. The regression coefficients of baseline CRP for the two periods were 1.41 (95% confidence interval [CI] 0.21-2.61 and 2.62 (95% CI 0.25-4.98, respectively, after adjusting for sex, age, baseline UPDRS-III score, dementia, and incremental L-dopa equivalent dose.Baseline plasma CRP levels were associated with motor deterioration and predicted motor prognosis in patients with PD. These associations were independent of sex, age, PD severity, dementia, and anti-Parkinsonian agents, suggesting that subclinical systemic inflammations could accelerate neurodegeneration in PD.

  17. The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L

    Science.gov (United States)

    Assis, L. H. P.; Silva-Junior, R. M. P.; Dolce, L. G.; Alborghetti, M. R.; Honorato, R. V.; Nascimento, A. F. Z.; Melo-Hanchuk, T. D.; Trindade, D. M.; Tonoli, C. C. C.; Santos, C. T.; Oliveira, P. S. L.; Larson, R. E.; Kobarg, J.; Espreafico, E. M.; Giuseppe, P. O.; Murakami, M. T.

    2017-01-01

    Myosin Va (MyoVa) is an actin-based molecular motor abundantly found at the centrosome. However, the role of MyoVa at this organelle has been elusive due to the lack of evidence on interacting partners or functional data. Herein, we combined yeast two-hybrid screen, biochemical studies and cellular assays to demonstrate that MyoVa interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning. MyoVa binds to the C2 domains of RPGRIP1L via residues located near or in the Rab11a-binding site, a conserved site in the globular tail domain (GTD) from class V myosins. According to proximity ligation assays, MyoVa and RPGRIP1L can interact near the cilium base in ciliated RPE cells. Furthermore, we showed that RPE cells expressing dominant-negative constructs of MyoVa are mostly unciliated, providing the first experimental evidence about a possible link between this molecular motor and cilia-related processes. PMID:28266547

  18. Minus end-directed kinesin-like motor protein, Kcbp, localizes to anaphase spindle poles in Haemanthus endosperm.

    Science.gov (United States)

    Smirnova, E A; Reddy, A S; Bowser, J; Bajer, A S

    1998-01-01

    Microtubule-based motor proteins assemble and reorganize acentrosomal mitotic and meiotic spindles in animal cells. The functions of motor proteins in acentrosomal plant spindles are unknown. The cellulosic cell wall and relative small size of most plant cells precludes accurate detection of the spatial distribution of motors in mitosis. Large cell size and absence of a cellulosic cell wall in Haemanthus endosperm make these cells ideally suited for studies of the spatial distribution of motor proteins during cell division. Immunolocalization of a kinesin-like calmodulin-binding protein (KCBP) in Haemanthus endosperm revealed its mitotic distribution. KCBP appears first in association with the prophase spindle. Highly concentrated within the cores of individual kinetochore fibers, KCBP decorates microtubules of kinetochore-fibers through metaphase. By mid-anaphase (when a barrel-shaped spindle becomes convergent), the protein redistributes and accumulates at the spindle polar regions. In telophase, KCBP relocates toward the phragmoplast and cell plate. These data suggest a role for KCBP in anaphase spindle microtubule convergence, which assures coherence of kinetochore-fibers within each sister chromosome group. Increasing coherence of kinetochore-fibers prevents splitting within each sister chromosome group and formation of multinucleated cells.

  19. Centromere-associated protein E: a motor that puts the brakes on the mitotic checkpoint.

    Science.gov (United States)

    Wood, Kenneth W; Chua, Penelope; Sutton, David; Jackson, Jeffrey R

    2008-12-01

    Cell cycle checkpoints have long been recognized as important nodes for regulating cell proliferation and maintaining genomic integrity. These checkpoints are often altered in cancer and represent promising points for therapeutic intervention. Until recently, direct targeting of the mitotic checkpoint has been an untapped area for cancer drug discovery. Regulation of the mitotic checkpoint is complex, but many of the critical players have been identified and functionally characterized. A substantial number of these proteins can be localized to the kinetochore, a structure located at the centromeric region of each mitotic chromosome. The kinetochore mediates chromosome attachment to spindle microtubules and subsequent chromosome movement. The mitotic checkpoint monitors microtubule attachment and chromosome position on the mitotic spindle, inhibiting progression into anaphase until proper attachment and metaphase positioning is achieved. Centromere-associated protein E is a kinesin microtubule motor protein that plays an essential role in integrating the mechanics of microtubule-chromosome interactions with mitotic checkpoint signaling, and has emerged as a novel target for cancer therapy.

  20. Survival motor neuron protein regulates stem cell division, proliferation, and differentiation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Stuart J Grice

    2011-04-01

    Full Text Available Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 (SMN1 gene. SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death. It is currently unknown how the reduction of this ubiquitously essential protein can lead to tissue-specific abnormalities. In addition, it is still not known whether the disease is caused by developmental or degenerative defects. Using the Drosophila system, we show that SMN is enriched in postembryonic neuroblasts and forms a concentration gradient in the differentiating progeny. In addition to the developing Drosophila larval CNS, Drosophila larval and adult testes have a striking SMN gradient. When SMN is reduced in postembryonic neuroblasts using MARCM clonal analysis, cell proliferation and clone formation defects occur. These SMN mutant neuroblasts fail to correctly localise Miranda and have reduced levels of snRNAs. When SMN is removed, germline stem cells are lost more frequently. We also show that changes in SMN levels can disrupt the correct timing of cell differentiation. We conclude that highly regulated SMN levels are essential to drive timely cell proliferation and cell differentiation.

  1. Alteration of protein folding and degradation in motor neuron diseases : Implications and protective functions of small heat shock proteins

    NARCIS (Netherlands)

    Carra, Serena; Crippa, Valeria; Rusmini, Paola; Boncoraglio, Alessandra; Minoia, Melania; Giorgetti, Elisa; Kampinga, Harm H.; Poletti, Angelo

    2012-01-01

    Motor neuron diseases (MNDs) are neurodegenerative disorders that specifically affect the survival and function of upper and/or lower motor neurons. Since motor neurons are responsible for the control of voluntary muscular movement, MNDs are characterized by muscle spasticity, weakness and atrophy.

  2. Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson's disease.

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    Ding, Jian; Zhang, Jiejin; Wang, Xixi; Zhang, Li; Jiang, Siming; Yuan, Yongsheng; Li, Junyi; Zhu, Lin; Zhang, Kezhong

    2017-03-01

    The aim of our study is to examine the plasma levels of the four kinds of neurodegenerative proteins in plasma: α-syn, T-tau, P-tau181, and Aβ-42 in Parkinson's disease (PD) and to evaluate the relationship between their plasma levels and PD motor subtypes. 84 patients with PD were enrolled in our study, and finally, 73 of them were classified into the tremor-dominant subtype (TD) and the postural instability gait difficulty subtype (PIGD). Their motor performance was evaluated by a series of clinical assessments: Freezing of Gait Questionnaire (FOGQ), Timed Up and Go (TUGs), Tinetti balance, and Tinetti gait. Plasma levels of these proteins were measured by enzyme-linked immunosorbent assay (ELISA). The plasma level of α-syn was significantly higher in PD patients when compared to controls (p = 0.004), and significantly higher in the PIGD group when compared to the TD group (p = 0.03). While the plasma level of Aβ-42 was significantly lower in PD patients than in controls (p = 0.002), and significantly lower in the PIGD group than in the TD group (p = 0.05). In PD patients, the plasma level of α-syn (r = -0.355, p score, even after performing multiple linear regression (p = 0.002). While the plasma level of Aβ-42 (r = -0.261, p score and remained correlate when performed multiple linear regression (p = 0.005). The patients with PIGD subtype are characterized with a lower level of plasma Aβ-42 and a higher plasma level of α-syn, which may be used as biomarkers for diagnosis and progression of the subtypes of PD.

  3. Tug of War in Motor Protein Ensembles Revealed with a Programmable DNA Origami Scaffold

    Science.gov (United States)

    Derr, N. D.; Goodman, B. S.; Jungmann, R.; Leschziner, A. E.; Shih, W. M.; Reck-Peterson, S. L.

    2013-01-01

    Cytoplasmic dynein and kinesin-1 are opposite-polarity, microtubule-based motors that transport a wide variety of cargo in eukaryotic cells. Many cellular cargos demonstrate bi-directional movement due to the presence of ensembles of dynein and kinesin, but are ultimately sorted with spatial and temporal precision. To investigate the mechanisms that coordinate motor ensemble behavior, we built a programmable synthetic cargo using three-dimensional DNA origami to which varying numbers of DNA oligonucleotide-linked motors could be attached, allowing control of motor type, number, spacing, and orientation in vitro. In ensembles of 1–7 identical-polarity motors, motor number had minimal affect on directional velocity, while ensembles of opposite-polarity motors engaged in a tug of war resolvable by disengaging one motor species. PMID:23065903

  4. Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration.

    Science.gov (United States)

    Sellers, Drew L; Bergen, Jamie M; Johnson, Russell N; Back, Heidi; Ravits, John M; Horner, Philip J; Pun, Suzie H

    2016-03-01

    A significant unmet need in treating neurodegenerative disease is effective methods for delivery of biologic drugs, such as peptides, proteins, or nucleic acids into the central nervous system (CNS). To date, there are no operative technologies for the delivery of macromolecular drugs to the CNS via peripheral administration routes. Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAxI), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection. In animals with transected peripheral nerve roots, TAxI delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS. Notably, TAxI-Cre recombinase fusion proteins induced selective recombination and tdTomato-reporter expression in motor neurons after intramuscular injections. Furthermore, TAxI peptide was shown to label motor neurons in the human tissue. The demonstration of a nonviral-mediated delivery of functional proteins into the spinal cord establishes the clinical potential of this technology for minimally invasive administration of CNS-targeted therapeutics.

  5. Selective cell-surface labeling of the molecular motor protein prestin

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, Ryan M. [Department of Bioengineering, Rice University, Houston, TX 77251 (United States); Silberg, Jonathan J., E-mail: joff@rice.edu [Department of Bioengineering, Rice University, Houston, TX 77251 (United States); Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251 (United States); Pereira, Fred A. [Department of Bioengineering, Rice University, Houston, TX 77251 (United States); Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Raphael, Robert M., E-mail: rraphael@rice.edu [Department of Bioengineering, Rice University, Houston, TX 77251 (United States)

    2011-06-24

    Highlights: {yields} Trafficking to the plasma membrane is required for prestin function. {yields} Biotin acceptor peptide (BAP) was fused to prestin through a transmembrane domain. {yields} BAP-prestin can be metabolically labeled with biotin in HEK293 cells. {yields} Biotin-BAP-prestin allows for selective imaging of fully trafficked prestin. {yields} The biotin-BAP-prestin displays voltage-sensitive activity. -- Abstract: Prestin, a multipass transmembrane protein whose N- and C-termini are localized to the cytoplasm, must be trafficked to the plasma membrane to fulfill its cellular function as a molecular motor. One challenge in studying prestin sequence-function relationships within living cells is separating the effects of amino acid substitutions on prestin trafficking, plasma membrane localization and function. To develop an approach for directly assessing prestin levels at the plasma membrane, we have investigated whether fusion of prestin to a single pass transmembrane protein results in a functional fusion protein with a surface-exposed N-terminal tag that can be detected in living cells. We find that fusion of the biotin-acceptor peptide (BAP) and transmembrane domain of the platelet-derived growth factor receptor (PDGFR) to the N-terminus of prestin-GFP yields a membrane protein that can be metabolically-labeled with biotin, trafficked to the plasma membrane, and selectively detected at the plasma membrane using fluorescently-tagged streptavidin. Furthermore, we show that the addition of a surface detectable tag and a single-pass transmembrane domain to prestin does not disrupt its voltage-sensitive activity.

  6. Importance of anisotropy in detachment rates for force production and cargo transport by a team of motor proteins.

    Science.gov (United States)

    Takshak, Anjneya; Kunwar, Ambarish

    2016-05-01

    Many cellular processes are driven by collective forces generated by a team consisting of multiple molecular motor proteins. One aspect that has received less attention is the detachment rate of molecular motors under mechanical force/load. While detachment rate of kinesin motors measured under backward force increases rapidly for forces beyond stall-force; this scenario is just reversed for non-yeast dynein motors where detachment rate from microtubule decreases, exhibiting a catch-bond type behavior. It has been shown recently that yeast dynein responds anisotropically to applied load, i.e. detachment rates are different under forward and backward pulling. Here, we use computational modeling to show that these anisotropic detachment rates might help yeast dynein motors to improve their collective force generation in the absence of catch-bond behavior. We further show that the travel distance of cargos would be longer if detachment rates are anisotropic. Our results suggest that anisotropic detachment rates could be an alternative strategy for motors to improve the transport properties and force production by the team.

  7. Protein Misdirection Inside and Outside Motor Neurons in Amyotrophic Lateral Sclerosis (ALS: A Possible Clue for Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Akemi Ido

    2011-10-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating neurodegenerative disease characterized by progressive muscle wasting and weakness with no effective cure. Emerging evidence supports the notion that the abnormal conformations of ALS-linked proteins play a central role in triggering the motor neuron degeneration. In particular, mutant types of superoxide dismutase 1 (SOD1 and TAR DNA binding protein 43kDa (TDP-43 are key molecules involved in the pathogenesis of familial and sporadic ALS, respectively. The commonalities of the two proteins include a propensity to aggregate and acquire detrimental conformations through oligomerization, fragmentation, or post-translational modification that may drive abnormal subcellular localizations. Although SOD1 is a major cytosolic protein, mutated SOD1 has been localized to mitochondria, endoplasmic reticulum, and even the extracellular space. The nuclear exclusion of TDP-43 is a pathological hallmark for ALS, although the pathogenic priority remains elusive. Nevertheless, these abnormal behaviors based on the protein misfolding are believed to induce diverse intracellular and extracellular events that may be tightly linked to non-cell-autonomous motor neuron death. The generation of mutant- or misfolded protein-specific antibodies would help to uncover the distribution and propagation of the ALS-linked proteins, and to design a therapeutic strategy to clear such species. Herein we review the literature regarding the mislocalization of ALS-linked proteins, especially mutant SOD1 and TDP-43 species, and discuss the rationale of molecular targeting strategies including immunotherapy.

  8. Dysregulated striatal neuronal processing and impaired motor behavior in mice lacking huntingtin interacting protein 14 (HIP14.

    Directory of Open Access Journals (Sweden)

    Ana María Estrada-Sánchez

    Full Text Available Palmitoyl acyl transferases (PATs play a critical role in protein trafficking and function. Huntingtin interacting protein 14 (HIP14 is a PAT that acts on proteins associated with neuronal transmission, suggesting that deficient protein palmitoylation by HIP14, which occurs in the YAC128 model of Huntington's disease (HD, might have deleterious effects on neurobehavioral processing. HIP14 knockout mice show biochemical and neuropathological changes in the striatum, a forebrain region affected by HD that guides behavioral choice and motor flexibility. Thus, we evaluated the performance of these mice in two tests of motor ability: nest-building and plus maze turning behavior. Relative to wild-type controls, HIP14 knockout mice show impaired nest building and decreased turning in the plus maze. When we recorded the activity of striatal neurons during plus-maze performance, we found faster firing rates and dysregulated spike bursting in HIP14 knockouts compared to wild-type. There was also less correlated firing between simultaneously recorded neuronal pairs in the HIP14 knockouts. Overall, our results indicate that HIP14 is critically involved in behavioral modulation of striatal processing. In the absence of HIP14, striatal neurons become dysfunctional, leading to impaired motor behavior.

  9. Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

    Science.gov (United States)

    Murashov, A. K.; Talebian, S.; Wolgemuth, D. J.

    1998-01-01

    Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

  10. Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

    Science.gov (United States)

    Murashov, A. K.; Talebian, S.; Wolgemuth, D. J.

    1998-01-01

    Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

  11. Molecular determinants of survival motor neuron (SMN protein cleavage by the calcium-activated protease, calpain.

    Directory of Open Access Journals (Sweden)

    Jennifer L Fuentes

    Full Text Available Spinal muscular atrophy (SMA is a leading genetic cause of childhood mortality, caused by reduced levels of survival motor neuron (SMN protein. SMN functions as part of a large complex in the biogenesis of small nuclear ribonucleoproteins (snRNPs. It is not clear if defects in snRNP biogenesis cause SMA or if loss of some tissue-specific function causes disease. We recently demonstrated that the SMN complex localizes to the Z-discs of skeletal and cardiac muscle sarcomeres, and that SMN is a proteolytic target of calpain. Calpains are implicated in muscle and neurodegenerative disorders, although their relationship to SMA is unclear. Using mass spectrometry, we identified two adjacent calpain cleavage sites in SMN, S192 and F193. Deletion of small motifs in the region surrounding these sites inhibited cleavage. Patient-derived SMA mutations within SMN reduced calpain cleavage. SMN(D44V, reported to impair Gemin2 binding and amino-terminal SMN association, drastically inhibited cleavage, suggesting a role for these interactions in regulating calpain cleavage. Deletion of A188, a residue mutated in SMA type I (A188S, abrogated calpain cleavage, highlighting the importance of this region. Conversely, SMA mutations that interfere with self-oligomerization of SMN, Y272C and SMNΔ7, had no effect on cleavage. Removal of the recently-identified SMN degron (Δ268-294 resulted in increased calpain sensitivity, suggesting that the C-terminus of SMN is important in dictating availability of the cleavage site. Investigation into the spatial determinants of SMN cleavage revealed that endogenous calpains can cleave cytosolic, but not nuclear, SMN. Collectively, the results provide insight into a novel aspect of the post-translation regulation of SMN.

  12. The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET.

    Science.gov (United States)

    Ho, James; Sielaff, Hendrik; Nadeem, Aftab; Svanborg, Catharina; Grüber, Gerhard

    2015-05-22

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected. As shown by fluorescence correlation spectroscopy, HAMLET binds to the F1 domain of the F1F0 ATP synthase with a dissociation constant (KD) of 20.5μM. Increasing concentrations of the tumoricidal protein HAMLET added to the enzymatically active α3β3γ complex of the F-ATP synthase lowered its ATPase activity, demonstrating that HAMLET binding to the F-ATP synthase effects the catalysis of this molecular motor. Single-molecule analysis was applied to study HAMLET-α3β3γ complex interaction. Whereas the α3β3γ complex of the F-ATP synthase rotated in a counterclockwise direction with a mean rotational rate of 3.8±0.7s(-1), no rotation could be observed in the presence of bound HAMLET. Our findings suggest that direct effects of HAMLET on the F-ATP synthase may inhibit ATP-dependent cellular processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Effects of motor patterns on water-soluble and membrane proteins and cholinesterase activity in subcellular fractions of rat brain tissue

    Science.gov (United States)

    Pevzner, L. Z.; Venkov, L.; Cheresharov, L.

    1980-01-01

    Albino rats were kept for a year under conditions of daily motor load or constant hypokinesia. An increase in motor activity results in a rise in the acetylcholinesterase activity determined in the synaptosomal and purified mitochondrial fractions while hypokinesia induces a pronounced decrease in this enzyme activity. The butyrylcholinesterase activity somewhat decreases in the synaptosomal fraction after hypokinesia but does not change under the motor load pattern. Motor load causes an increase in the amount of synaptosomal water-soluble proteins possessing an intermediate electrophoretic mobility and seem to correspond to the brain-specific protein 14-3-2. In the synaptosomal fraction the amount of membrane proteins with a low electrophoretic mobility and with the cholinesterase activity rises. Hypokinesia, on the contrary, decreases the amount of these membrane proteins.

  14. KIFC1-like motor protein associates with the cephalopod manchette and participates in sperm nuclear morphogenesis in Octopus tankahkeei.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available BACKGROUND: Nuclear morphogenesis is one of the most fundamental cellular transformations taking place during spermatogenesis. In rodents, a microtubule-based perinuclear structure, the manchette, and a C-terminal kinesin motor KIFC1 are believed to play crucial roles in this process. Spermatogenesis in Octopus tankahkeei is a good model system to explore whether evolution has created a cephalopod prototype of mammalian manchette-based and KIFC1-dependent sperm nuclear shaping machinery. METHODOLOGY/PRINCIPAL FINDINGS: We detected the presence of a KIFC1-like protein in the testis, muscle, and liver of O. tankahkeei by Western Blot. Then we tracked its dynamic localization in spermatic cells at various stages using Immunofluorescence and Immunogold Electron Microscopy. The KIFC1-like protein was not expressed at early stages of spermatogenesis when no significant morphological changes occur, began to be present in early spermatid, localized around and in the nucleus of intermediate and late spermatids where the nucleus was dramatically elongated and compressed, and concentrated at one end of final spermatid. Furthermore, distribution of the motor protein during nuclear elongation and condensation overlapped with that of the cephalopod counterpart of manchette at a significant level. CONCLUSIONS/SIGNIFICANCE: The results support the assumption that the protein is actively involved in sperm nuclear morphogenesis in O. tankahkeei possibly through bridging the manchette-like perinuclear microtubules to the nucleus and assisting in the nucleocytoplasmic trafficking of specific cargoes. This study represents the first description of the role of a motor protein in sperm nuclear shaping in cephalopod.

  15. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons.

    Science.gov (United States)

    Moldovan, Mihai; Alvarez, Susana; Pinchenko, Volodymyr; Klein, Dennis; Nielsen, Finn Cilius; Wood, John N; Martini, Rudolf; Krarup, Christian

    2011-02-01

    Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage gated sodium channel isoform, which is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold tracking' excitability studies with conventional nerve conduction studies, behavioural studies using rotor-rod measurements, and histological measures to assess membrane dysfunction and its progression in protein zero deficient homozygous mutants as compared with age-matched wild-type controls. The involvement of Na(V)1.8 was investigated by pharmacologic block using the subtype-selective Na(V)1.8 blocker A-803467 and chronically in Na(V)1.8 knock-outs. We found that in the context of dysmyelination, abnormal potassium ion currents and membrane depolarization, the ectopic Na(V)1.8 channels further impair the motor axon excitability in protein zero deficient homozygous mutants to an extent that precipitates conduction failure in severely affected axons. Our data suggest that a Na(V)1.8 channelopathy contributed to the poor motor function of protein zero deficient homozygous mutants, and that the conduction failure was associated with partially reversible reduction of the electrically evoked muscle response and of the clinical function as indicated by the partial recovery of function at rotor-rod measurements. As a

  16. Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobility.

    Science.gov (United States)

    Santos-Sacchi, Joseph; Zhao, Hong-Bo

    2003-08-01

    The outer hair cell motor protein, prestin, which resides exclusively in the cell's lateral membrane, underlies the mammal's exquisite sense of hearing. Here we show that photoexposure of the commonly used dyes Lucifer yellow, 6-carboxy-fluorescein, and 4-(2-[6-(dioctylamino)-2-naphthalenyl]ethenyl)-1-(3-sulfopropyl)-pyridinium (di-8-ANEPPS), that are in contact with the cell's lateral membrane can photo-inactivate the motor irreversibly, as evidenced by reduction in prestin's gating charge displacement or non-linear capacitance. Furthermore, utilizing restricted fiber optic illumination of the lateral membrane, we show that whole-cell, non-linear capacitance is depleted beyond that expected for an immobile population in the exposed area. These data indicate that lateral diffusion of prestin occurs within the cell's lateral plasma membrane.

  17. Viral and cellular SOS-regulated motor proteins: dsDNA translocation mechanisms with divergent functions.

    Science.gov (United States)

    Wolfe, Annie; Phipps, Kara; Weitao, Tao

    2014-01-01

    DNA damage attacks on bacterial cells have been known to activate the SOS response, a transcriptional response affecting chromosome replication, DNA recombination and repair, cell division and prophage induction. All these functions require double-stranded (ds) DNA translocation by ASCE hexameric motors. This review seeks to delineate the structural and functional characteristics of the SOS response and the SOS-regulated DNA translocases FtsK and RuvB with the phi29 bacteriophage packaging motor gp16 ATPase as a prototype to study bacterial motors. While gp16 ATPase, cellular FtsK and RuvB are similarly comprised of hexameric rings encircling dsDNA and functioning as ATP-driven DNA translocases, they utilize different mechanisms to accomplish separate functions, suggesting a convergent evolution of these motors. The gp16 ATPase and FtsK use a novel revolution mechanism, generating a power stroke between subunits through an entropy-DNA affinity switch and pushing dsDNA inward without rotation of DNA and the motor, whereas RuvB seems to employ a rotation mechanism that remains to be further characterized. While FtsK and RuvB perform essential tasks during the SOS response, their roles may be far more significant as SOS response is involved in antibiotic-inducible bacterial vesiculation and biofilm formation as well as the perspective of the bacteria-cancer evolutionary interaction.

  18. The UNC-4 homeobox protein represses mab-9 expression in DA motor neurons in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Jafari, Gholamali; Appleford, Peter J; Seago, Julian;

    2011-01-01

    The T-box transcription factor mab-9 has been shown to be required for the correct fate of the male-specific blast cells B and F, normal posterior hypodermal morphogenesis, and for the correct axon migration of motor neurons that project circumferential commissures to dorsal muscles. In this stud...

  19. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration

    NARCIS (Netherlands)

    Simpson, Claire L.; Lemmens, Robin; Miskiewicz, Katarzyna; Broom, Wendy J.; Hansen, Valerie K.; van Vught, Paul W. J.; Landers, John E.; Sapp, Peter; Van Den Bosch, Ludo; Knight, Joanne; Neale, Benjamin M.; Turner, Martin R.; Veldink, Jan H.; Ophoff, Roel A.; Tripathi, Vineeta B.; Beleza, Ana; Shah, Meera N.; Proitsi, Petroula; Van Hoecke, Annelies; Carmeliet, Peter; Horvitz, H. Robert; Leigh, P. Nigel; Shaw, Christopher E.; van den Berg, Leonard H.; Sham, Pak C.; Powell, John F.; Verstreken, Patrik; Brown, Robert H.; Robberecht, Wim; Al-Chalabi, Ammar

    2009-01-01

    Amyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both

  20. NanoShuttles: Harnessing Motor Proteins to Transport Cargo in Synthetic Environments

    Science.gov (United States)

    Vogel, V.; Hess, H.

    Motors have become a crucial commodity in our daily lives, from transportation to driving conveyor belts that enable the sequential assembly of cars and other industrial machines. For the sequential assembly of building blocks at the nanoscale that would not assemble spontaneously into larger functional systems, however, active transport systems are not yet available. In contrast, cells have evolved sophisticated molecular machinery that drives movement and active transport. Driven by the conversion of chemical into mechanical energy, namely through hydrolysis of the biological fuel ATP, molecular motors enable cells to operate far away from equilibrium by transporting organelles and molecules to designated locations within the cell, often against concentration gradients. Inspired by the biological concept of active transport, major efforts are underway to learn how to build nanoscale transport systems that are driven by molecular motors. Emerging engineering principles are discussed of how to build tracks and junctions to guide such nanoshuttles, how to load them with cargo and control their speed, how to use active transport to assemble mesoscopic structures that would otherwise not assemble spontaneously and what polymeric materials to choose to integrate motors into MEMS and other biohybrid devices. Finally, two applications that exploit the physical properties of microtubules are discussed, surface imaging by a swarm of microtubules and a self-assembled picoNewton force meter to probe receptor-ligand interactions.

  1. The family of mammalian small heat shock proteins (HSPBs) : Implications in protein deposit diseases and motor neuropathies

    NARCIS (Netherlands)

    Boncoraglio, Alessandra; Minoia, Melania; Carra, Serena

    2012-01-01

    A number of neurological and muscular disorders are characterized by the accumulation of aggregate-prone proteins and are referred to as protein deposit or protein conformation diseases. Besides some sporadic forms, most of them are genetically inherited in an autosomal dominant manner, although rec

  2. The family of mammalian small heat shock proteins (HSPBs) : Implications in protein deposit diseases and motor neuropathies

    NARCIS (Netherlands)

    Boncoraglio, Alessandra; Minoia, Melania; Carra, Serena

    2012-01-01

    A number of neurological and muscular disorders are characterized by the accumulation of aggregate-prone proteins and are referred to as protein deposit or protein conformation diseases. Besides some sporadic forms, most of them are genetically inherited in an autosomal dominant manner, although

  3. Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish

    Directory of Open Access Journals (Sweden)

    Yang Song

    2013-03-01

    Mutations in patatin-like phospholipase domain containing 6 (PNPLA6, also known as neuropathy target esterase (NTE or SPG39, cause hereditary spastic paraplegia (HSP. Although studies on animal models, including mice and Drosophila, have extended our understanding of PNPLA6, its roles in neural development and in HSP are not clearly understood. Here, we describe the generation of a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio. Pnpla6 knockdown resulted in developmental abnormalities and motor neuron defects, including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrate an important role of PNPLA6 in motor neuron development and implicate overexpression of BMP signaling as a possible mechanism underlying the developmental defects in pnpla6 morphants.

  4. Survival of motor neurone protein is required for normal postnatal development of the spleen.

    Science.gov (United States)

    Thomson, Alison K; Somers, Eilidh; Powis, Rachael A; Shorrock, Hannah K; Murphy, Kelley; Swoboda, Kathryn J; Gillingwater, Thomas H; Parson, Simon H

    2017-02-01

    Spinal muscular atrophy (SMA), traditionally described as a predominantly childhood form of motor neurone disease, is the leading genetic cause of infant mortality. Although motor neurones are undoubtedly the primary affected cell type, the severe infantile form of SMA (Type I SMA) is now widely recognised to represent a multisystem disorder where a variety of organs and systems in the body are also affected. Here, we report that the spleen is disproportionately small in the 'Taiwanese' murine model of severe SMA (Smn(-/-) ;SMN2(tg/0) ), correlated to low levels of cell proliferation and increased cell death. Spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganised fibrotic architecture. Histologically distinct white pulp failed to form and this was reflected in an almost complete absence of B lymphocytes necessary for normal immune function. In addition, megakaryoctyes persisted in the red pulp. However, the vascular density remained unchanged in SMA spleen. Assessment of the spleen in SMA patients with the infantile form of the disease indicated a range of pathologies. We conclude that development of the spleen fails to occur normally in SMA mouse models and human patients. Thus, further analysis of immune function is likely to be required to fully understand the full extent of systemic disease pathology in SMA.

  5. Dual interaction of scaffold protein Tim44 of mitochondrial import motor with channel-forming translocase subunit Tim23.

    Science.gov (United States)

    Ting, See-Yeun; Yan, Nicholas L; Schilke, Brenda A; Craig, Elizabeth A

    2017-04-25

    Proteins destined for the mitochondrial matrix are targeted to the inner membrane Tim17/23 translocon by their presequences. Inward movement is driven by the matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the matrix face of the translocon, recruits other motor subunits and binds incoming presequence. The basis of these interactions and their functional relationships remains unclear. Using site-specific in vivo crosslinking and genetic approaches in Saccharomyces cerevisiae, we found that both domains of Tim44 interact with the major matrix-exposed loop of Tim23, with the C-terminal domain (CTD) binding Tim17 as well. Results of in vitro experiments showed that the N-terminal domain (NTD) is intrinsically disordered and binds presequence near a region important for interaction with Hsp70 and Tim23. Our data suggest a model in which the CTD serves primarily to anchor Tim44 to the translocon, whereas the NTD is a dynamic arm, interacting with multiple components to drive efficient translocation.

  6. An oral Na(V)1.8 blocker improves motor function in mice completely deficient of myelin protein P-0

    DEFF Research Database (Denmark)

    Rosberg, Mette R.; Alvarez Herrero, Susana; Krarup, Christian

    2016-01-01

    -/-, a CMT model with a much more severe neuropathy. We found that the progressive impairment of motor performance from 1 to 4 months of age in P0-/- could be acutely reversed by C31 treatment. The effect was associated with an improvement of the amplitude of the plantar CMAP evoked by tibial nerve...... stimulation. The corresponding motor nerve excitability studies by “threshold tracking” showed changes after C31 consistent with attenuation of a resting membrane depolarization. Our data suggest that the depolarizing motor conduction failure in P0-/- could be acutely improved by C31. This provides proof......Mice deficient of myelin protein P0 are established models of demyelinating Charcot-Marie-Tooth (CMT) disease. Dysmyelination in these mice is associated with an ectopic expression of the sensory neuron specific sodium channel isoform NaV1.8 on motor axons. We reported that in P0+/−, a model of CMT...

  7. Drosophila Torsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein

    Directory of Open Access Journals (Sweden)

    Phuong Nguyen

    2016-01-01

    Full Text Available We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor by DTor-specific inhibitory double-stranded RNA (RNAi induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH. Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved.

  8. Single Molecule Analysis of the Arabidopsis FRA1 Kinesin Shows that It Is a Functional Motor Protein with Unusually High Processivity

    Institute of Scientific and Technical Information of China (English)

    Chuanmei Zhu; Ram Dixit

    2011-01-01

    The Arabidopsis FRA1 kinesin contributes to the organization of cellulose microfibrils through an unknown mechanism.The cortical localization of this kinesin during interphase raises the possibility that it transports cell wallrelated cargoes along cortical microtubules that either directly or indirectly influence cellulose microfibril patterning.To determine whether FRA1 is an authentic motor protein,we combined bulk biochemical assays and single molecule fluorescence imaging to analyze the motor properties of recombinant,GFP-tagged FRA1 containing the motor and coiled-coil domains (designated as FRA1(707)-GFP).We found that FRA1(707)-GFP binds to microtubules in an ATP-dependent manner and that its ATPase activity is dramatically stimulated by the presence of microtubules.Using single molecule studies,we found that FRA1(707)-GFP moves processively along microtubule tracks at a velocity of about 0.4 μm s-1.In addition,we found that FRA1(707)-GFP is a microtubule plus-end-directed motor and that it moves along microtubules as a dimer.Interestingly,our single molecule analysis shows that the processivity of FRA1(707)-GFP is at least twice the processivity of conventional kinesin,making FRA1 the most processive kinesin to date.Together,our data show that FRA1 is a bona fide motor protein that has the potential to drive long-distance transport of cargo along cortical microtubules.

  9. G-protein-coupled receptor 30-mediated antiapoptotic effect of estrogen on spinal motor neurons following injury and its underlying mechanisms.

    Science.gov (United States)

    Chen, Jingyu; Hu, Rong; Ge, Hongfei; Duanmu, Wangsheng; Li, Yuhong; Xue, Xingseng; Hu, Shengli; Feng, Hua

    2015-08-01

    Spinal cord injury (SCI) may result in severe dysfunction of motor neurons. G-protein-coupled receptor 30 (GPR30) expression in the motor neurons of the ventral horn of the spinal cord mediates neuroprotection through estrogen signaling. The present study explored the antiapoptotic effect of estrogen, mediated by GPR30 following SCI, and the mechanisms underlying this effect. Spinal motor neurons from rats were cultured in vitro in order to establish cell models of oxygen and glucose deprivation (OGD). The effects of estrogen, the estrogen agonist, G1, and the estrogen inhibitor, G15, on motor neurons were observed using MTT assays. The effects of E2, G1 and G15 on spinal motor neuron apoptosis following OGD, were detected using flow cytometry. The role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) inhibitor, LY294002, was also determined using flow cytometry. Rat SCI models were established. E2, G1 and E2+LY294002 were administered in vivo. Motor function was scored at 3, 7, 14, 21 and 28 d following injury, using Basso-Beattie-Bresnahan (BBB) standards. Cell activity in the estrogen and G1 groups was higher than that in the solvent group, whereas cell activity in the E2+G15 group was lower than that in the E2 group (Pestrogen group was significantly lower than that in the solvent group, whereas the proportion of apoptotic cells in the E2+G15 and E2+LY294002 groups was higher than that in the E2 group (PEstrogen thus appears to exert a protective effect on spinal motor neurons following OGD, via GPR30. The PI3K/Akt pathway may be one of those involved in the estrogen‑related antiapoptotic effects mediated by GPR30.

  10. The actin-binding protein capulet genetically interacts with the microtubule motor kinesin to maintain neuronal dendrite homeostasis.

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    Paul M B Medina

    Full Text Available BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.

  11. D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16 and the R7 binding protein RSBP-1 in Caenoerhabditis elegans motor neurons.

    Directory of Open Access Journals (Sweden)

    Khursheed A Wani

    Full Text Available Dopamine signaling modulates voluntary movement and reward-driven behaviors by acting through G protein-coupled receptors in striatal neurons, and defects in dopamine signaling underlie Parkinson's disease and drug addiction. Despite the importance of understanding how dopamine modifies the activity of striatal neurons to control basal ganglia output, the molecular mechanisms that control dopamine signaling remain largely unclear. Dopamine signaling also controls locomotion behavior in Caenorhabditis elegans. To better understand how dopamine acts in the brain we performed a large-scale dsRNA interference screen in C. elegans for genes required for endogenous dopamine signaling and identified six genes (eat-16, rsbp-1, unc-43, flp-1, grk-1, and cat-1 required for dopamine-mediated behavior. We then used a combination of mutant analysis and cell-specific transgenic rescue experiments to investigate the functional interaction between the proteins encoded by two of these genes, eat-16 and rsbp-1, within single cell types and to examine their role in the modulation of dopamine receptor signaling. We found that EAT-16 and RSBP-1 act together to modulate dopamine signaling and that while they are coexpressed with both D1-like and D2-like dopamine receptors, they do not modulate D2 receptor signaling. Instead, EAT-16 and RSBP-1 act together to selectively inhibit D1 dopamine receptor signaling in cholinergic motor neurons to modulate locomotion behavior.

  12. D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16 and the R7 binding protein RSBP-1 in Caenoerhabditis elegans motor neurons.

    Science.gov (United States)

    Wani, Khursheed A; Catanese, Mary; Normantowicz, Robyn; Herd, Muriel; Maher, Kathryn N; Chase, Daniel L

    2012-01-01

    Dopamine signaling modulates voluntary movement and reward-driven behaviors by acting through G protein-coupled receptors in striatal neurons, and defects in dopamine signaling underlie Parkinson's disease and drug addiction. Despite the importance of understanding how dopamine modifies the activity of striatal neurons to control basal ganglia output, the molecular mechanisms that control dopamine signaling remain largely unclear. Dopamine signaling also controls locomotion behavior in Caenorhabditis elegans. To better understand how dopamine acts in the brain we performed a large-scale dsRNA interference screen in C. elegans for genes required for endogenous dopamine signaling and identified six genes (eat-16, rsbp-1, unc-43, flp-1, grk-1, and cat-1) required for dopamine-mediated behavior. We then used a combination of mutant analysis and cell-specific transgenic rescue experiments to investigate the functional interaction between the proteins encoded by two of these genes, eat-16 and rsbp-1, within single cell types and to examine their role in the modulation of dopamine receptor signaling. We found that EAT-16 and RSBP-1 act together to modulate dopamine signaling and that while they are coexpressed with both D1-like and D2-like dopamine receptors, they do not modulate D2 receptor signaling. Instead, EAT-16 and RSBP-1 act together to selectively inhibit D1 dopamine receptor signaling in cholinergic motor neurons to modulate locomotion behavior.

  13. Spinocerebellar ataxia type 6 protein aggregates cause deficits in motor learning and cerebellar plasticity.

    Science.gov (United States)

    Mark, Melanie D; Krause, Martin; Boele, Henk-Jan; Kruse, Wolfgang; Pollok, Stefan; Kuner, Thomas; Dalkara, Deniz; Koekkoek, Sebastiaan; De Zeeuw, Chris I; Herlitze, Stefan

    2015-06-10

    Spinocerebellar ataxia type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming subunits of P/Q-type Ca(2+) channels (Cav2.1) and is characterized by CT protein aggregates found in cerebellar Purkinje cells (PCs). One hypothesis regarding SCA6 disease is that a CT fragment of the Cav2.1 channel, which is detected specifically in cytosolic and nuclear fractions in SCA6 patients, is associated with the SCA6 pathogenesis. To test this hypothesis, we expressed P/Q-type channel protein fragments from two different human CT splice variants, as predicted from SCA6 patients, in PCs of mice using viral and transgenic approaches. These splice variants represent a short (CT-short without polyQs) and a long (CT-long with 27 polyQs) CT fragment. Our results show that the different splice variants of the CTs differentially distribute within PCs, i.e., the short CTs reveal predominantly nuclear inclusions, whereas the long CTs prominently reveal both nuclear and cytoplasmic aggregates. Postnatal expression of CTs in PCs in mice reveals that only CT-long causes SCA6-like symptoms, i.e., deficits in eyeblink conditioning (EBC), ataxia, and PC degeneration. The physiological phenotypes associated specifically with the long CT fragment can be explained by an impairment of LTD and LTP at the parallel fiber-to-PC synapse and alteration in spontaneous PC activity. Thus, our results suggest that the polyQ carrying the CT fragment of the P/Q-type channel is sufficient to cause SCA6 pathogenesis in mice and identifies EBC as a new diagnostic strategy to evaluate Ca(2+) channel-mediated human diseases.

  14. Interaction of motor proteins of various types at melanosome redistribution in melanocytes under action of UV radiation

    Science.gov (United States)

    Stolnitz, Mikhail M.; Kudryashov, Alexey A.

    2004-05-01

    In the report the mathematical model of melanosome transport along filaments in intact and UV-irradiated melanocytes is submitted. Processes at three levels are considered: dynamics of the single motor, transport of melanosome by ensemble of motors, and melanosomes distribution along microtubules. A single motor is considered as > modeling of transitions between internal states described by chemical kinetics equations allows to determine "force-velocity" dependence for motor. The ensemble of motors is described by system of equations for average motor velocities, and transported melanosome moves with average velocity, which in turn is determined by sum of force generated by each elastic-coupled motor (self-consistence problem). Distribution of melanosomes along a microtubule is described by system of equations for bidirectional motion of attached melanosome under coordinated action of "plus-end" and "minus-end" motors and free diffusion of unattached melanosomes. Influence of UV-radiation is resulted in change of number of each type motors simultaneously linked to one melanosome. It induces redistribution of melanosomes between centre and periphery of melanocyte.

  15. Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice.

    Science.gov (United States)

    Wincott, Charlotte M; Kim, Seonil; Titcombe, Roseann F; Tukey, David S; Girma, Hiwot K; Pick, Joseph E; Devito, Loren M; Hofmann, Franz; Hoeffer, Charles; Ziff, Edward B

    2013-01-01

    Activity-dependent trafficking of AMPA receptors to synapses regulates synaptic strength. Activation of the NMDA receptor induces several second messenger pathways that contribute to receptor trafficking-dependent plasticity, including the NO pathway, which elevates cGMP. In turn, cGMP activates the cGMP-dependent protein kinase type II (cGKII), which phosphorylates the AMPA receptor subunit GluA1 at serine 845, a critical step facilitating synaptic delivery in the mechanism of activity-dependent synaptic potentiation. Since cGKII is expressed in the striatum, amygdala, cerebral cortex, and hippocampus, it has been proposed that mice lacking cGKII may present phenotypic differences compared to their wild-type littermates in emotion-dependent tasks, learning and memory, and drug reward salience. Previous studies have shown that cGKII KO mice ingest higher amounts of ethanol as well as exhibit elevated anxiety levels compared to wild-type (WT) littermates. Here, we show that cGKII KO mice are significantly deficient in spatial learning while exhibiting facilitated motor coordination, demonstrating a clear dependence of memory-based tasks on cGKII. We also show diminished GluA1 phosphorylation in the postsynaptic density (PSD) of cGKII KO prefrontal cortex while in hippocampal PSD fractions, phosphorylation was not significantly altered. These data suggest that the role of cGKII may be more robust in particular brain regions, thereby impacting complex behaviors dependent on these regions differently.

  16. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Directory of Open Access Journals (Sweden)

    Gareth W Morgan

    2010-02-01

    Full Text Available Vaccinia virus (VACV uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC, a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs. Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD motif, which is conserved in the kinesin-1-binding sequence (KBS of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  17. Collective motor dynamics in membrane transport in vitro

    NARCIS (Netherlands)

    Shaklee, Paige Marie

    2009-01-01

    Key cellular processes such as cell division, internal cellular organization, membrane compartmentalization and intracellular transport rely on motor proteins. Motor proteins, ATP-based mechanoenzymes, actively transport cargo throughout the cell by walking on cytoskeletal filaments. Motors have bee

  18. Triptolide increases transcript and protein levels of survival motor neurons in human SMA fibroblasts and improves survival in SMA-like mice.

    Science.gov (United States)

    Hsu, Ya-Yun; Jong, Yuh-Jyh; Tsai, Hsin-Hung; Tseng, Yu-Ting; An, Li-Mei; Lo, Yi-Ching

    2012-06-01

    Spinal muscular atrophy (SMA) is a progressive neuromuscular disease. Since disease severity is related to the amount of survival motor neuron (SMN) protein, up-regulated functional SMN protein levels from the SMN2 gene are considered a major SMA drug-discovery strategy. In this study, we investigated the possible effects of triptolide, a diterpene triepoxide purified from Tripterygium wilfordii Hook. F., as a new compound for increasing SMN protein. The effects and mechanisms of triptolide on the production of SMA protein were determined by cell-based assays using the motor neuronal cell line NSC34 and skin fibroblasts from SMA patients. Wild-type (Smn(+/+) SMN2(-/-) , C57BL/6) and SMA-like (Smn(-/-) SMN2) mice were injected with triptolide (0.01 or 0.1 mg·kg(-1) ·day(-1) , i.p.) and their survival rate and level of change in SMN protein in neurons and muscle tissue measured. In NSC34 cells and human SMA fibroblasts, pM concentrations of triptolide significantly increased SMN protein expression and the levels of SMN complex component (Gemin2 and Gemin3). In human SMA fibroblasts, triptolide increased SMN-containing nuclear gems and the ratio of full-length transcripts (FL-SMN2) to SMN2 transcripts lacking exon 7 (SMN2Δ7). Furthermore, in SMA-like mice, triptolide significantly increased SMN protein levels in the brain, spinal cord and gastrocnemius muscle. Furthermore, triptolide treatment increased survival and reduced weight loss in SMA-like mice. Triptolide enhanced SMN protein production by promoting SMN2 activation, exon 7 inclusion and increasing nuclear gems, and increased survival in SMA mice, which suggests triptolide might be a potential candidate for SMA therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  19. Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Spires Tara L

    2008-04-01

    Full Text Available Abstract Background Huntington's disease (HD is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line, expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit. Results We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks, with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running. Conclusion These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment

  20. A network of HSPG core proteins and HS modifying enzymes regulates netrin-dependent guidance of D-type motor neurons in Caenorhabditis elegans.

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    Stephan Gysi

    Full Text Available Heparan sulfate proteoglycans (HSPGs are proteins with long covalently attached sugar side chains of the heparan sulfate (HS type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1 and Glypican (LON-2 and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons.

  1. A Network of HSPG Core Proteins and HS Modifying Enzymes Regulates Netrin-Dependent Guidance of D-Type Motor Neurons in Caenorhabditis elegans

    Science.gov (United States)

    Gysi, Stephan; Rhiner, Christa; Flibotte, Stephane; Moerman, Donald G.; Hengartner, Michael O.

    2013-01-01

    Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons. PMID:24066155

  2. In vivo neuron-wide analysis of synaptic vesicle precursor trafficking.

    Science.gov (United States)

    Maeder, Celine I; San-Miguel, Adriana; Wu, Emily Ye; Lu, Hang; Shen, Kang

    2014-03-01

    During synapse development, synaptic proteins must be targeted to sites of presynaptic release. Directed transport as well as local sequestration of synaptic vesicle precursors (SVPs), membranous organelles containing many synaptic proteins, might contribute to this process. Using neuron-wide time-lapse microscopy, we studied SVP dynamics in the DA9 motor neuron in Caenorhabditis elegans. SVP transport was highly dynamic and bi-directional throughout the entire neuron, including the dendrite. While SVP trafficking was anterogradely biased in axonal segments prior to the synaptic domain, directionality of SVP movement was stochastic in the dendrite and distal axon. Furthermore, frequency of movement and speed were variable between different compartments. These data provide evidence that SVP transport is differentially regulated in distinct neuronal domains. It also suggests that polarized SVP transport in concert with local vesicle capturing is necessary for accurate presynapse formation and maintenance. SVP trafficking analysis of two hypomorphs for UNC-104/KIF1A in combination with mathematical modeling identified directionality of movement, entry of SVPs into the axon as well as axonal speeds as the important determinants of steady-state SVP distributions. Furthermore, detailed dissection of speed distributions for wild-type and unc-104/kif1a mutant animals revealed an unexpected role for UNC-104/KIF1A in dendritic SVP trafficking.

  3. Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene

    DEFF Research Database (Denmark)

    Rosberg, Mette Romer; Alvarez, Susana; Krarup, Christian

    2013-01-01

    threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated...... axons with only a borderline impairment in conduction and Rotor-Rod. Plantar muscle reinnervation occurred within 21 days in all mice. Shortly after reinnervation the conduction of P0+/- regenerated axons was markedly slower than WT, however, this difference decayed with time. Nevertheless, after 1...... month, regenerated P0+/- axons had longer strength-duration time constant, larger threshold changes during hyperpolarizing electrotonus and longer relative refractory period. Their performance at Rotor-Rod remained also markedly impaired. In contrast, the number and diameter distribution of regenerating...

  4. Changes in synapse quantity and growth associated protein 43 expression in the motor cortex of focal cerebral ischemic rats following catalpol treatment

    Institute of Scientific and Technical Information of China (English)

    Dong Wan; Huifeng Zhu; Yong Luo; Peng Xie

    2011-01-01

    The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia. A rat model of focal permanent brain ischemia was established using electrocoagulation. The rats were intraperitoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week. Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.

  5. Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in rat model of ischemic-hypoxic brain injury

    Institute of Scientific and Technical Information of China (English)

    Liping Zhang; Liping Zou

    2008-01-01

    BACKGROUND: Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function, and these positive effects might be due to neural plasticity. OBJECTIVE: Myelin basic protein (MBP), microtubule-associated protein 2 (MAP2), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) were selected as markers of neural remodeling, and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment. DESIGN, TIME AND SETTING: A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007. MATERIALS: Twenty-four Sprague Dawley rat pups, aged 7 days, were selected for the present experiment. The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS: All animals were randomly divided into three groups: sham operation, model, and electro-acupuncture treatment, with 8 rats in each group. Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury. Upon model established, rats underwent hypobaric oxygen intervention for 24 hours. Only the left common carotid artery was exposed in rats of the sham operation group, without model establishment or oxygen intervention. The rats in the electro-acupuncture treatment group were treated with electro-acupuncture. One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint. The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second, as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second. Maximal current through the two dectrodes was limited to 3-5 mA. The stimulation lasted for 30 minutes per day for 2 weeks. Rats in the sham operation and model groups were not treated

  6. Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.

    Science.gov (United States)

    Zhai, Jinbin; Lin, Hong; Julien, Jean-Pierre; Schlaepfer, William W

    2007-12-15

    Mutations in neurofilament light (NFL) subunit and small heat-shock protein B1 (HSPB1) cause autosomal-dominant axonal Charcot-Marie-Tooth disease type 2E (CMT2E) and type 2F (CMT2F). Previous studies have shown that CMT mutations in NFL and HSPB1 disrupt NF assembly and cause aggregation of NFL protein. In this study, we investigate the role of aggregation of NFL protein in the neurotoxicity of CMT mutant NFL and CMT mutant HSPB1 in motor neurons. We find that expression of CMT mutant NFL leads to progressive degeneration and loss of neuronal viability of cultured motor neurons. Degenerating motor neurons show fragmentation and loss of neuritic processes associated with disruption of NF network and aggregation of NFL protein. Co-expression of wild-type HSPB1 diminishes aggregation of CMT mutant NFL, induces reversal of CMT mutant NFL aggregates and reduces CMT mutant NFL-induced loss of motor neuron viability. Like CMT mutant NFL, expression of S135F CMT mutant HSPB1 also leads to progressive degeneration of motor neurons with disruption of NF network and aggregation of NFL protein. Further studies show that wild-type and S135F mutant HSPB1 associate with wild-type and CMT mutant NFL and that S135F mutant HSPB1 has dominant effect on disruption of NF assembly and aggregation of NFL protein. Finally, we show that deletion of NFL markedly reduces degeneration and loss of motor neuron viability induced by S135F mutant HSPB1. Together, our data support the view that disruption of NF network with aggregation of NFL is a common triggering event of motor neuron degeneration in CMT2E and CMT2F disease.

  7. KIFC1-Like Motor Protein Associates with the Cephalopod Manchette and Participates in Sperm Nuclear Morphogenesis in Octopus tankahkeei

    OpenAIRE

    Wei Wang; Jun-Quan Zhu; He-Ming Yu; Fu-Qing Tan; Wan-Xi Yang

    2010-01-01

    BACKGROUND: Nuclear morphogenesis is one of the most fundamental cellular transformations taking place during spermatogenesis. In rodents, a microtubule-based perinuclear structure, the manchette, and a C-terminal kinesin motor KIFC1 are believed to play crucial roles in this process. Spermatogenesis in Octopus tankahkeei is a good model system to explore whether evolution has created a cephalopod prototype of mammalian manchette-based and KIFC1-dependent sperm nuclear shaping machinery. METH...

  8. Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Basso, Manuela; Pozzi, Silvia; Tortarolo, Massimo; Fiordaliso, Fabio; Bisighini, Cinzia; Pasetto, Laura; Spaltro, Gabriella; Lidonnici, Dario; Gensano, Francesco; Battaglia, Elisa; Bendotti, Caterina; Bonetto, Valentina

    2013-05-31

    Amyotrophic lateral sclerosis is the most common motor neuron disease and is still incurable. The mechanisms leading to the selective motor neuron vulnerability are still not known. The interplay between motor neurons and astrocytes is crucial in the outcome of the disease. We show that mutant copper-zinc superoxide dismutase (SOD1) overexpression in primary astrocyte cultures is associated with decreased levels of proteins involved in secretory pathways. This is linked to a general reduction of total secreted proteins, except for specific enrichment in a number of proteins in the media, such as mutant SOD1 and valosin-containing protein (VCP)/p97. Because there was also an increase in exosome release, we can deduce that astrocytes expressing mutant SOD1 activate unconventional secretory pathways, possibly as a protective mechanism. This may help limit the formation of intracellular aggregates and overcome mutant SOD1 toxicity. We also found that astrocyte-derived exosomes efficiently transfer mutant SOD1 to spinal neurons and induce selective motor neuron death. We conclude that the expression of mutant SOD1 has a substantial impact on astrocyte protein secretion pathways, contributing to motor neuron pathology and disease spread.

  9. Regulation of jaw-specific isoforms of myosin-binding protein-C and tropomyosin in regenerating cat temporalis muscle innervated by limb fast and slow motor nerves.

    Science.gov (United States)

    Kang, Lucia H D; Hoh, Joseph F Y

    2010-11-01

    Cat jaw-closing muscles are a distinct muscle allotype characterized by the expression of masticatory-specific myofibrillar proteins. Transplantation studies showed that expression of masticatory myosin heavy chain (m-MyHC) is promoted by fast motor nerves, but suppressed by slow motor nerves. We investigated whether masticatory myosin-binding protein-C (m-MBP-C) and masticatory tropomyosin (m-Tm) are similarly regulated. Temporalis muscle strips were transplanted into limb muscle beds to allow innervation by fast or slow muscle nerve during regeneration. Regenerated muscles were examined postoperatively up to 168 days by peroxidase IHC using monoclonal antibodies to m-MyHC, m-MBP-C, and m-Tm. Regenerates in both muscle beds expressed fetal and slow MyHCs, m-MyHC, m-MBP-C, and m-Tm during the first 4 weeks. Longer-term regenerates innervated by fast nerve suppressed fetal and slow MyHCs, retaining m-MyHC, m-MBP-C, and m-Tm, whereas fibers innervated by slow nerve suppressed fetal MyHCs and the three masticatory-specific proteins, induced slow MyHC, and showed immunohistochemical characteristics of jaw-slow fibers. We concluded that expression of m-MBP-C and m-Tm is coregulated by m-MyHC and that neural impulses to limb slow muscle are capable of suppressing masticatory-specific proteins and to channel gene expression along the jaw-slow phenotype unique to jaw-closing muscle.

  10. Characterization of Mutants of Human Small Heat Shock Protein HspB1 Carrying Replacements in the N-Terminal Domain and Associated with Hereditary Motor Neuron Diseases.

    Directory of Open Access Journals (Sweden)

    Lydia K Muranova

    Full Text Available Physico-chemical properties of the mutations G34R, P39L and E41K in the N-terminal domain of human heat shock protein B1 (HspB1, which have been associated with hereditary motor neuron neuropathy, were analyzed. Heat-induced aggregation of all mutants started at lower temperatures than for the wild type protein. All mutations decreased susceptibility of the N- and C-terminal parts of HspB1 to chymotrypsinolysis. All mutants formed stable homooligomers with a slightly larger apparent molecular weight compared to the wild type protein. All mutations analyzed decreased or completely prevented phosphorylation-induced dissociation of HspB1 oligomers. When mixed with HspB6 and heated, all mutants yielded heterooligomers with apparent molecular weights close to ~400 kDa. Finally, the three HspB1 mutants possessed lower chaperone-like activity towards model substrates (lysozyme, malate dehydrogenase and insulin compared to the wild type protein, conversely the environmental probe bis-ANS yielded higher fluorescence with the mutants than with the wild type protein. Thus, in vitro the analyzed N-terminal mutations increase stability of large HspB1 homooligomers, prevent their phosphorylation-dependent dissociation, modulate their interaction with HspB6 and decrease their chaperoning capacity, preventing normal functioning of HspB1.

  11. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways. The catalog of the intrinsic response properties, their underlying mechanisms, and regulation obtained from motoneurons...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  12. Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer׳s disease.

    Science.gov (United States)

    Kishimoto, Yasushi; Shishido, Hajime; Sawanishi, Mayumi; Toyota, Yasunori; Ueno, Masaki; Kubota, Takashi; Kirino, Yutaka; Tamiya, Takashi; Kawai, Nobuyuki

    2016-12-01

    This data article contains supporting information regarding the research article entitled "Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer׳s disease" (H. Shishido, Y. Kishimoto, N. Kawai, Y. Toyota, M. Ueno, T. Kubota, Y. Kirino, T. Tamiya, 2016) [1]. Triple-transgenic (3×Tg)-Alzheimer׳s disease (AD) model mice exhibited significantly poorer spatial learning than sham-treated 3×Tg-AD mice 28 days after traumatic brain injury (TBI). Correspondingly, amyloid-β (Aβ) deposition within the hippocampus was significantly greater in 3×Tg-AD mice 28 days after TBI. However, data regarding the short-term and long-term influences of TBI on amyloid precursor protein (APP) accumulation in AD model mice remain limited. Furthermore, there is little data showing whether physical activity and motor learning are affected by TBI in AD model mice. Here, we provide immunocytochemistry data confirming that TBI induces significant increases in APP accumulation in 3×Tg-AD mice at both 7 days and 28 days after TBI. Furthermore, 3×Tg-AD model mice exhibit a reduced ability to acquire conditioned responses (CRs) during delay eyeblink conditioning compared to sham-treated 3×Tg-AD model mice 28 days after TBI. However, physical activity and motor performance are not significantly changed in TBI-treated 3×Tg-AD model mice.

  13. Motor syndromes.

    Science.gov (United States)

    Corea, Francesco; Micheli, Sara

    2012-01-01

    Motor disturbances alone or associated with other focal deficits are the most common symptoms suggesting a neurovascular event. An appropriate clinical assessment of these signs and symptoms may help physicians to better diagnose and to both better treat and predict outcome. In this paper the main clinical features of motor deficit are described together with other motor-related events such as ataxia and movement disturbances.

  14. Progressive motor deficit is mediated by the denervation of neuromuscular junctions and axonal degeneration in transgenic mice expressing mutant (P301S) tau protein

    NARCIS (Netherlands)

    Yin, Zhuoran; Valkenburg, Femke; Hornix, Betty E; Mantingh-Otter, Ietje; Zhou, Xingdong; Mari, Muriel; Reggiori, Fulvio; Van Dam, Debby; Eggen, Bart J L; De Deyn, Peter P; Boddeke, Erik

    2017-01-01

    Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we

  15. Progressive motor deficit is mediated by the denervation of neuromuscular junctions and axonal degeneration in transgenic mice expressing mutant (P301S) tau protein

    NARCIS (Netherlands)

    Yin, Zhuoran; Valkenburg, Femke; Hornix, Betty E; Mantingh-Otter, Ietje; Zhou, Xingdong; Mari, Muriel; Reggiori, Fulvio; Van Dam, Debby; Eggen, Bart J L; De Deyn, Peter P; Boddeke, Erik

    2017-01-01

    Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we

  16. Protective effect of parvalbumin on excitotoxic motor neuron death

    DEFF Research Database (Denmark)

    Van den Bosch, L.; Schwaller, B.; Vleminckx, V.

    2002-01-01

    Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin......Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin...

  17. The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type

    Science.gov (United States)

    Choi, Seong-Kyoon; Huh, Yang Hoon; Fang, Zi; Park, Seo Jin; Kim, Myoung Ok; Ryoo, Zae Young; Kang, Kyeongjin; Kweon, Hee-Seok; Jeon, Won Bae; Li, Chris; Kim, Kyuhyung

    2015-01-01

    The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In C. elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In lim-4 mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the flp-12 neuropeptide gene, is completely abolished and thus the function of the SMB neurons is compromised. LIM-4 activity promotes SMB identity by directly regulating the expression of the SMB marker genes via a distinct cis-regulatory motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM-4 in C. elegans. Furthermore, C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in the human neuronal cell lines. Our results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain proteins function in generation of precise neuronal subtypes. PMID:26305787

  18. Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats.

    Science.gov (United States)

    Zhang, Bei; He, Qiang; Li, Ying-Ying; Li, Ce; Bai, Yu-Long; Hu, Yong-Shan; Zhang, Feng

    2015-12-01

    Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT) involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of 'learned non-use' and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model) group, a CIMT + model (CIMT) group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

  19. Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

    Directory of Open Access Journals (Sweden)

    Bei Zhang

    2015-01-01

    Full Text Available Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of ′learned non-use′ and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model group, a CIMT + model (CIMT group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

  20. Chloride-driven electromechanical phase lags at acoustic frequencies are generated by SLC26a5, the outer hair cell motor protein.

    Science.gov (United States)

    Santos-Sacchi, Joseph; Song, Lei

    2014-07-01

    Outer hair cells (OHC) possess voltage-dependent membrane bound molecular motors, identified as the solute carrier protein SLC26a5, that drive somatic motility at acoustic frequencies. The electromotility (eM) of OHCs provides for cochlear amplification, a process that enhances auditory sensitivity by up to three orders of magnitude. In this study, using whole cell voltage clamp and mechanical measurement techniques, we identify disparities between voltage sensing and eM that result from stretched exponential electromechanical behavior of SLC26a5, also known as prestin, for its fast responsiveness. This stretched exponential behavior, which we accurately recapitulate with a new kinetic model, the meno presto model of prestin, influences the protein's responsiveness to chloride binding and provides for delays in eM relative to membrane voltage driving force. The model predicts that in the frequency domain, these delays would result in eM phase lags that we confirm by measuring OHC eM at acoustic frequencies. These lags may contribute to canceling viscous drag, a requirement for many models of cochlear amplification. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Major facilitator superfamily domain-containing protein 2a (MFSD2A has roles in body growth, motor function, and lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Justin H Berger

    Full Text Available The metabolic adaptations to fasting in the liver are largely controlled by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα, where PPARα upregulates genes encoding the biochemical pathway for β-oxidation of fatty acids and ketogenesis. As part of an effort to identify and characterize nutritionally regulated genes that play physiological roles in the adaptation to fasting, we identified Major facilitator superfamily domain-containing protein 2a (Mfsd2a as a fasting-induced gene regulated by both PPARα and glucagon signaling in the liver. MFSD2A is a cell-surface protein homologous to bacterial sodium-melibiose transporters. Hepatic expression and turnover of MFSD2A is acutely regulated by fasting/refeeding, but expression in the brain is constitutive. Relative to wildtype mice, gene-targeted Mfsd2a knockout mice are smaller, leaner, and have decreased serum, liver and brown adipose triglycerides. Mfsd2a knockout mice have normal liver lipid metabolism but increased whole body energy expenditure, likely due to increased β-oxidation in brown adipose tissue and significantly increased voluntary movement, but surprisingly exhibited a form of ataxia. Together, these results indicate that MFSD2A is a nutritionally regulated gene that plays myriad roles in body growth and development, motor function, and lipid metabolism. Moreover, these data suggest that the ligand(s that are transported by MFSD2A play important roles in these physiological processes and await future identification.

  2. Activation of Growth-associated Protein by Intragastric Brazilein in Motor Neuron of Spinal Cord Connected with Injured Sciatic Nerve in Mice

    Institute of Scientific and Technical Information of China (English)

    CAO Jian; LI Li-sen; LIU Biao; LIU Hao-yu; ZHANG Hui; ZHAO Ming-ming; YIN Wei-tian

    2011-01-01

    The purpose of this study is to explore the expression of growth-associated protein(GAP-43) in spinal cord segments connected with injured sciatic nerve by the treatment with brazilein in mice. Unilateral sciatic nerve interruption and anastomosis were performed. Physiological saline(blank group), high dose, middle dose and low dose of brazilein were administrated intragastrically to healthy adult BALB/c mice in separate groups. L4-6 spinal segments connected with the sciatic nerve were harvested. Real-time PCR(Polymerase chain reaction) and Western blot analysis were performed to detect the expression of GAP-43 in spinal segments. Histological staining on myelin and the electrophysiology were performed to examine the sciatic nerve recovery. GAP-43 was activated in spinal cord L4-6 connected with injured sciatic nerve. In the survival time of 12 h, 24 h, 3 d, 5 d, 7 d and 14 d, GAP-43 expression in the motor neurons of spinal cord of the high dose group and that in the middle dose group were significantly higher than those on the low dose and blank groups. Myelin in the high dose group and that in the middle dose group were more mature and the potential amplitude and MNCV(motor nerve conduction velocity) in the high and middle dose groups were obviously higher than those in the low dose group and blank group. Brazilein facilitates the expression of GAP-43 in neurons in spinal cord L4-6 segments connected with injured sciatic nerve, which promotes nerve regeneration.

  3. Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

    Directory of Open Access Journals (Sweden)

    Loy Clement T

    2008-08-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

  4. Motor homopolar

    OpenAIRE

    Agustín Martín Muñoz

    2007-01-01

    Mostramos la construcción de un modelo de motor homopolar, uno de los más antiguos tipos de motores eléctricos. Se caracterizan porque el campo magnético del imán mantiene siempre la misma polaridad (de ahí su nombre, del griego homos, igual), de modo que, cuando una corriente eléctrica atraviesa el campo magnético, aparece una fuerza que hace girar los elementos no fijados mecánicamente. En el sencillísimo motor homopolar colgado (Schlichting y Ucke 2004), el imán puede girar ...

  5. A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice.

    Directory of Open Access Journals (Sweden)

    Fotis Ioakeimidis

    Full Text Available Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases.

  6. A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice.

    Science.gov (United States)

    Ioakeimidis, Fotis; Ott, Christine; Kozjak-Pavlovic, Vera; Violitzi, Foteini; Rinotas, Vagelis; Makrinou, Eleni; Eliopoulos, Elias; Fasseas, Costas; Kollias, George; Douni, Eleni

    2014-01-01

    Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases.

  7. Ultrasonic Motors

    Science.gov (United States)

    2003-06-01

    and T. Higuchi, "Cylindrical Micro Ultrasonic Motor Utilizing Bulk Lead Zirconate Titanate (PZT)," Japanese Journal of Applied Physics Part 1-Regular Papers Short Notes & Review Papers, vol. 38, pp. 3347-3350, 1999.

  8. The Maize Divergent spindle-1 (dv1) Gene Encodes a Kinesin-14A Motor Protein Required for Meiotic Spindle Pole Organization.

    Science.gov (United States)

    Higgins, David M; Nannas, Natalie J; Dawe, R Kelly

    2016-01-01

    The classic maize mutant divergent spindle-1 (dv1) causes failures in meiotic spindle assembly and a decrease in pollen viability. By analyzing two independent dv1 alleles we demonstrate that this phenotype is caused by mutations in a member of the kinesin-14A subfamily, a class of C-terminal, minus-end directed microtubule motors. Further analysis demonstrates that defects in early spindle assembly are rare, but that later stages of spindle organization promoting the formation of finely focused spindle poles are strongly dependent on Dv1. Anaphase is error-prone in dv1 lines but not severely so, and the majority of cells show normal chromosome segregation. Live-cell imaging of wild type and mutant plants carrying CFP-tagged β-tubulin confirm that meiosis in dv1 lines fails primarily at the pole-sharpening phase of spindle assembly. These data indicate that plant kinesin-14A proteins help to enforce bipolarity by focusing spindle poles and that this stage of spindle assembly is not required for transition through the spindle checkpoint but improves the accuracy of chromosome segregation.

  9. Association of copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein gene with the natural history in a Chinese spinal muscular atrophy cohort.

    Science.gov (United States)

    Qu, Yu-jin; Ge, Xiu-shan; Bai, Jin-li; Wang, Li-wen; Cao, Yan-yan; Lu, Yan-yu; Jin, Yu-wei; Wang, Hong; Song, Fang

    2015-03-01

    We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP.

  10. The maize Divergent spindle-1 (dv1 gene encodes a kinesin-14A motor protein required for meiotic spindle pole organization

    Directory of Open Access Journals (Sweden)

    David M Higgins

    2016-08-01

    Full Text Available The classic maize mutant divergent spindle-1 (dv1 causes failures in meiotic spindle assembly and a decrease in pollen viability. By analyzing two independent dv1 alleles we demonstrate that this phenotype is caused by mutations in a member of the kinesin-14A subfamily, a class of C-terminal, minus-end directed microtubule motors. Further analysis demonstrates that defects in early spindle assembly are rare, but that later stages of spindle organization promoting the formation of finely focused spindle poles are strongly dependent on Dv1. Anaphase is error-prone in dv1 lines but not severely so, and the majority of cells show normal chromosome segregation. Live-cell imaging of wild type and mutant plants carrying CFP-tagged β-tubulin confirm that meiosis in dv1 lines fails primarily at the pole-sharpening phase of spindle assembly. These data indicate that plant kinesin-14A proteins help to enforce bipolarity by focusing spindle poles and that this stage of spindle assembly is not required for transition through the spindle checkpoint but improves the accuracy of chromosome segregation.

  11. Structural attributes for the recognition of weak and anomalous regions in coiled-coils of myosins and other motor proteins

    Directory of Open Access Journals (Sweden)

    Sunitha Margaret S

    2012-09-01

    Full Text Available Abstract Background Coiled-coils are found in different proteins like transcription factors, myosin tail domain, tropomyosin, leucine zippers and kinesins. Analysis of various structures containing coiled-coils has revealed the importance of electrostatic and hydrophobic interactions. In such domains, regions of different strength of interactions need to be identified since they could be biologically relevant. Findings We have updated our coiled-coil validation webserver, now called COILCHECK+, where new features were added to efficiently identify the strength of interaction at the interface region and measure the density of charged residues and hydrophobic residues. We have examined charged residues and hydrophobic ladders, using a new algorithm called CHAHO, which is incorporated within COILCHECK + server. CHAHO permits the identification of spatial charged residue patches and the continuity of hydrophobic ladder which stabilizes and destabilizes the coiled-coil structure. Conclusions The availability of such computational tools should be useful to understand the importance of spatial clustering of charged residues and the continuity of hydrophobic residues at the interface region of coiled-coil dimers. COILCHECK + is a structure based tool to validate coiled-coil stability; it can be accessed at http://caps.ncbs.res.in/coilcheckplus.

  12. Crystallographic and molecular dynamics analysis of loop motions unmasking the peptidoglycan-binding site in stator protein MotB of flagellar motor.

    Directory of Open Access Journals (Sweden)

    Cyril F Reboul

    Full Text Available BACKGROUND: The C-terminal domain of MotB (MotB-C shows high sequence similarity to outer membrane protein A and related peptidoglycan (PG-binding proteins. It is believed to anchor the power-generating MotA/MotB stator unit of the bacterial flagellar motor to the peptidoglycan layer of the cell wall. We previously reported the first crystal structure of this domain and made a puzzling observation that all conserved residues that are thought to be essential for PG recognition are buried and inaccessible in the crystal structure. In this study, we tested a hypothesis that peptidoglycan binding is preceded by, or accompanied by, some structural reorganization that exposes the key conserved residues. METHODOLOGY/PRINCIPAL FINDINGS: We determined the structure of a new crystalline form (Form B of Helicobacter pylori MotB-C. Comparisons with the existing Form A revealed conformational variations in the petal-like loops around the carbohydrate binding site near one end of the β-sheet. These variations are thought to reflect natural flexibility at this site required for insertion into the peptidoglycan mesh. In order to understand the nature of this flexibility we have performed molecular dynamics simulations of the MotB-C dimer. The results are consistent with the crystallographic data and provide evidence that the three loops move in a concerted fashion, exposing conserved MotB residues that have previously been implicated in binding of the peptide moiety of peptidoglycan. CONCLUSION/SIGNIFICANCE: Our structural analysis provides a new insight into the mechanism by which MotB inserts into the peptidoglycan mesh, thus anchoring the power-generating complex to the cell wall.

  13. Motor Planning.

    Science.gov (United States)

    Wong, Aaron L; Haith, Adrian M; Krakauer, John W

    2015-08-01

    Motor planning colloquially refers to any process related to the preparation of a movement that occurs during the reaction time prior to movement onset. However, this broad definition encompasses processes that are not strictly motor-related, such as decision-making about the identity of task-relevant stimuli in the environment. Furthermore, the assumption that all motor-planning processes require processing time, and can therefore be studied behaviorally by measuring changes in the reaction time, needs to be reexamined. In this review, we take a critical look at the processes leading from perception to action and suggest a definition of motor planning that encompasses only those processes necessary for a movement to be executed-that is, processes that are strictly movement related. These processes resolve the ambiguity inherent in an abstract goal by defining a specific movement to achieve it. We propose that the majority of processes that meet this definition can be completed nearly instantaneously, which means that motor planning itself in fact consumes only a small fraction of the reaction time. © The Author(s) 2014.

  14. Theoretical Analysis of Dynamic Processes for Interacting Molecular Motors.

    Science.gov (United States)

    Teimouri, Hamid; Kolomeisky, Anatoly B; Mehrabiani, Kareem

    2015-02-13

    Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. It allows us to connect explicitly microscopic features of motor proteins with their collective dynamic properties. Theoretical analysis that combines various mean-field calculations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions, and correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motors transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  15. Intramanchette transport during primate spermiogenesis:expression of dynein, myosin Va, motor recruiter myosin Va,Ⅶa-Rab27a/b interacting protein, and Rab27b in the manchette during human and monkey spermiogenesis

    Institute of Scientific and Technical Information of China (English)

    Shinichi Hayasaka; Yukihiro Terada; Kichiya Suzuki; Haruo Murakawa; Ikuo Tachibana; Tadashi Sankai; Takashi Murakami; Nobuo Yaegashi; Kunihiro Okamura

    2008-01-01

    Aim: To show whether molecular motor dynein on a microtubule track, molecular motor myosin Va, motor recruiter myosin Va, Ⅶa-Rab27a/b interacting protein (MyRIP), and vesicle receptor Rab27b on an F-actin track were present during human and monkey spermiogenesis involving intramanchette transport (IMT). Methods: Spermiogenic cells were obtained from three men with obstructive azoospermia and normal adult cynomolgus monkey (Macaca fascieularis). Immunocytochemical detection and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the pro- teins were carried out. Samples were analyzed by light microscope. Results: Using RT-PCR, we found that dynein, myosin Va, MyRIP and Rab27b were expressed in monkey testis. These proteins were localized to the manchette, as shown by immunofluorescence, particularly during human and monkey spermiogenesis. Conclusion: We speculate that during primate spermiogenesis, those proteins that compose microtubule-based and actin-based vesicle transport systems are actually present in the manchette and might possibly be involved in intramanchette transport. (Asian J Androl 2008 Jul; 10: 561-568)

  16. THE MOTOR

    DEFF Research Database (Denmark)

    Gammelgaard Nielsen, Anders

    2011-01-01

    MOTOR is the first assignment that students at Unit 1a of the School of Architecture are introduced to. The purpose of the assignment is to shake up the students and their preconceptions of what architec- ture is. This is done by introducing them to a working method that al- lows them to develop...

  17. THE MOTOR

    DEFF Research Database (Denmark)

    Gammelgaard Nielsen, Anders

    2011-01-01

    MOTOR is the first assignment that students at Unit 1a of the School of Architecture are introduced to. The purpose of the assignment is to shake up the students and their preconceptions of what architec- ture is. This is done by introducing them to a working method that al- lows them to develop...

  18. Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

    Science.gov (United States)

    Freund, Ronald K; Gibson, Emily S; Potter, Huntington; Dell'Acqua, Mark L

    2016-05-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aβ-induced synaptic dysfunction, but we recently found that Aβ(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aβ(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aβ, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aβ(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aβ(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0μM Aβ(1-42) or 1-5μM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aβon LTP and synapse loss, suggesting that Aβinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

  19. Protein

    Science.gov (United States)

    ... Food Service Resources Additional Resources About FAQ Contact Protein Protein is found throughout the body—in muscle, ... the heart and respiratory system, and death. All Protein Isn’t Alike Protein is built from building ...

  20. Progressive Motor Deficit is Mediated by the Denervation of Neuromuscular Junctions and Axonal Degeneration in Transgenic Mice Expressing Mutant (P301S) Tau Protein.

    Science.gov (United States)

    Yin, Zhuoran; Valkenburg, Femke; Hornix, Betty E; Mantingh-Otter, Ietje; Zhou, Xingdong; Mari, Muriel; Reggiori, Fulvio; Van Dam, Debby; Eggen, Bart J L; De Deyn, Peter P; Boddeke, Erik

    2017-02-10

    Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging. Hyperphosphorylated tau was detected in the cell bodies and axons of motor neurons. At the age of 9 and 12 months, significant denervation of the neuromuscular junction in the extensor digitorum longus muscle was observed in Tau 58/4 mice, compared to wild-type mice. Muscle hypotrophy was observed in Tau 58/4 mice at 9 and 12 months. Using electron microscopy, we observed ultrastructural changes in the sciatic nerve of 12-month-old Tau 58/4 mice indicative of the loss of large axonal fibers and hypomyelination (assessed by g-ratio). We conclude that the accumulated hyperphosphorylated tau in the axon terminals may induce dying-back axonal degeneration, myelin abnormalities, neuromuscular junction denervation, and muscular atrophy, which may be the mechanisms responsible for the deterioration of the motor function in Tau 58/4 mice. Tau 58/4 mice represent an interesting neuromuscular degeneration model, and the pathological mechanisms might be responsible for motor signs observed in some human tauopathies.

  1. Brain distribution of dipeptide repeat proteins in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72.

    Science.gov (United States)

    Davidson, Yvonne S; Barker, Holly; Robinson, Andrew C; Thompson, Jennifer C; Harris, Jenny; Troakes, Claire; Smith, Bradley; Al-Saraj, Safa; Shaw, Chris; Rollinson, Sara; Masuda-Suzukake, Masami; Hasegawa, Masato; Pickering-Brown, Stuart; Snowden, Julie S; Mann, David M

    2014-06-20

    A hexanucleotide (GGGGCC) expansion in C9ORF72 gene is the most common genetic change seen in familial Frontotemporal Lobar Degeneration (FTLD) and familial Motor Neurone Disease (MND). Pathologically, expansion bearers show characteristic p62 positive, TDP-43 negative inclusion bodies within cerebellar and hippocampal neurons which also contain dipeptide repeat proteins (DPR) formed from sense and antisense RAN (repeat associated non ATG-initiated) translation of the expanded repeat region itself. 'Inappropriate' formation, and aggregation, of DPR might therefore confer neurotoxicity and influence clinical phenotype. Consequently, we compared the topographic brain distribution of DPR in 8 patients with Frontotemporal dementia (FTD), 6 with FTD + MND and 7 with MND alone (all 21 patients bearing expansions in C9ORF72) using a polyclonal antibody to poly-GA, and related this to the extent of TDP-43 pathology in key regions of cerebral cortex and hippocampus. There were no significant differences in either the pattern or severity of brain distribution of DPR between FTD, FTD + MND and MND groups, nor was there any relationship between the distribution of DPR and TDP-43 pathologies in expansion bearers. Likewise, there were no significant differences in the extent of TDP-43 pathology between FTLD patients bearing an expansion in C9ORF72 and non-bearers of the expansion. There were no association between the extent of DPR pathology and TMEM106B or APOE genotypes. However, there was a negative correlation between the extent of DPR pathology and age at onset. Present findings therefore suggest that although the presence and topographic distribution of DPR may be of diagnostic relevance in patients bearing expansion in C9ORF72 this has no bearing on the determination of clinical phenotype. Because TDP-43 pathologies are similar in bearers and non-bearers of the expansion, the expansion may act as a major genetic risk factor for FTLD and MND by rendering the brain

  2. Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP‐43 pathology and not associated with aggregated forms of dipeptide repeat proteins

    OpenAIRE

    2015-01-01

    Aims A hexanucleotide expansion in C9orf72 is the major genetic cause of inherited behavioural variant Frontotemporal dementia (bvFTD) and motor neurone disease (MND), although the pathological mechanism(s) underlying disease remains uncertain. Methods Using antibodies to poly‐GA, poly‐GP, poly‐GR, poly‐AP and poly‐PR proteins, we examined sections of cerebral cortex, hippocampus, thalamus, cerebellum and spinal cord, from 20 patients with bvFTD and/or MND bearing an expansion in C9orf72 for ...

  3. Lipid - Motor Interactions: Soap Opera or Symphony?

    Science.gov (United States)

    Pathak, Divya; Mallik, Roop

    2017-02-01

    Intracellular transport of organelles can be driven by multiple motor proteins that bind to the lipid membrane of the organelle and work as a team. We review present knowledge on how lipids orchestrate the recruitment of motors to a membrane. Looking beyond recruitment, we also discuss how heterogeneity and local mechanical properties of the membrane may influence function of motor-teams. These issues gain importance because phagocytosed pathogens use lipid-centric strategies to manipulate motors and survive in host cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Gross motor control

    Science.gov (United States)

    Gross motor control is the ability to make large, general movements (such as waving an arm or lifting a leg). ... Gross motor control is a milestone in the development of an infant. Infants develop gross motor control before they develop ...

  5. Motor function in interpolar microtubules during metaphase

    OpenAIRE

    Deutsch, J. M.; Lewis, Ian P.

    2013-01-01

    We analyze experimental observations of microtubules undergoing small fluctuations about a "balance point" when mixed in solution of two different kinesin motor proteins, KLP61F and Ncd. It has been proposed that the microtubule movement is due to stochastic variations in the densities of the two species of motor proteins. We test this hypothesis here by showing how it maps onto a one-dimensional random walk in a random environment. Our estimate of the amplitude of the fluctuations agrees wit...

  6. Motor control for a brushless DC motor

    Science.gov (United States)

    Peterson, William J. (Inventor); Faulkner, Dennis T. (Inventor)

    1985-01-01

    This invention relates to a motor control system for a brushless DC motor having an inverter responsively coupled to the motor control system and in power transmitting relationship to the motor. The motor control system includes a motor rotor speed detecting unit that provides a pulsed waveform signal proportional to rotor speed. This pulsed waveform signal is delivered to the inverter to thereby cause an inverter fundamental current waveform output to the motor to be switched at a rate proportional to said rotor speed. In addition, the fundamental current waveform is also pulse width modulated at a rate proportional to the rotor speed. A fundamental current waveform phase advance circuit is controllingly coupled to the inverter. The phase advance circuit is coupled to receive the pulsed waveform signal from the motor rotor speed detecting unit and phase advance the pulsed waveform signal as a predetermined function of motor speed to thereby cause the fundamental current waveform to be advanced and thereby compensate for fundamental current waveform lag due to motor winding reactance which allows the motor to operate at higher speeds than the motor is rated while providing optimal torque and therefore increased efficiency.

  7. The Maize Divergent spindle-1 (dv1) Gene Encodes a Kinesin-14A Motor Protein Required for Meiotic Spindle Pole Organization

    OpenAIRE

    Higgins, David M.; Nannas, Natalie J.; R Kelly Dawe

    2016-01-01

    The classic maize mutant divergent spindle-1 (dv1) causes failures in meiotic spindle assembly and a decrease in pollen viability. By analyzing two independent dv1 alleles we demonstrate that this phenotype is caused by mutations in a member of the kinesin-14A subfamily, a class of C-terminal, minus-end directed microtubule motors. Further analysis demonstrates that defects in early spindle assembly are rare, but that later stages of spindle organization promoting the formation of finely focu...

  8. SMN is required for sensory-motor circuit function in Drosophila.

    Science.gov (United States)

    Imlach, Wendy L; Beck, Erin S; Choi, Ben Jiwon; Lotti, Francesco; Pellizzoni, Livio; McCabe, Brian D

    2012-10-12

    Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous survival motor neuron (SMN) protein. Drosophila SMN mutants have reduced muscle size and defective locomotion, motor rhythm, and motor neuron neurotransmission. Unexpectedly, restoration of SMN in either muscles or motor neurons did not alter these phenotypes. Instead, SMN must be expressed in proprioceptive neurons and interneurons in the motor circuit to nonautonomously correct defects in motor neurons and muscles. SMN depletion disrupts the motor system subsequent to circuit development and can be mimicked by the inhibition of motor network function. Furthermore, increasing motor circuit excitability by genetic or pharmacological inhibition of K(+) channels can correct SMN-dependent phenotypes. These results establish sensory-motor circuit dysfunction as the origin of motor system deficits in this SMA model and suggest that enhancement of motor neural network activity could ameliorate the disease.

  9. High efficiency motors; Motores de alta eficiencia

    Energy Technology Data Exchange (ETDEWEB)

    Uranga Favela, Ivan Jaime [Energia Controlada de Mexico, S. A. de C. V., Mexico, D. F. (Mexico)

    1992-12-31

    This paper is a technical-financial study of the high efficiency and super-premium motors. As it is widely known, more than 60% of the electrical energy generated in the country is used for the operation of motors, in industry as well as in commerce. Therefore the importance that the motors have in the efficient energy use. [Espanol] El presente trabajo es un estudio tecnico-financiero de los motores de alta eficiencia y los motores super premium. Como es ampliamente conocido, mas del 60% de la energia electrica generada en el pais, es utilizada para accionar motores, dentro de la industria y el comercio. De alli la importancia que los motores tienen en el uso eficiente de la energia.

  10. A reconsideration of the link between the energetics of water and of ATP hydrolysis energy in the power strokes of molecular motors in protein structures.

    Science.gov (United States)

    Widdas, Wilfred F

    2008-09-01

    Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick's work, energetics were revised by Joule's experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration.

  11. Motor Priming in Neurorehabilitation

    OpenAIRE

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2015-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few ...

  12. Motor Priming in Neurorehabilitation

    OpenAIRE

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2015-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few ...

  13. Motor neuropathies and lower motor neuron syndromes.

    Science.gov (United States)

    Verschueren, A

    2017-05-01

    Motor or motor-predominant neuropathies may arise from disease processes affecting the motor axon and/or its surrounding myelin. Lower motor neuron syndrome (LMNS) arises from a disease process affecting the spinal motor neuron itself. The term LMNS is more generally used, rather than motor neuronopathy, although both entities are clinically similar. Common features are muscle weakness (distal or proximal) with atrophy and hyporeflexia, but no sensory involvement. They can be acquired or hereditary. Immune-mediated neuropathies (multifocal motor neuropathy, motor-predominant chronic inflammatory demyelinating polyneuropathy) are important to identify, as effective treatments are available. Other acquired neuropathies, such as infectious, paraneoplastic and radiation-induced neuropathies are also well known. Focal LMNS is an amyotrophic lateral sclerosis (ALS)-mimicking syndrome especially affecting young adults. The main hereditary LMNSs in adulthood are Kennedy's disease, late-onset spinal muscular atrophy and distal hereditary motor neuropathies. Motor neuropathies and LMNS are all clinical entities that should be better known, despite being rare diseases. They can sometimes be difficult to differentially diagnose from other diseases, particularly from the more frequent ALS in its pure LMN form. Nevertheless, correct identification of these syndromes is important because their treatment and prognoses are definitely different. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Cargo transport by several motors

    CERN Document Server

    Zhang, Yunxin

    2010-01-01

    In cells, organelles and vesicles are usually transported by cooperation of several motor proteins, including plus-end directed motor kinesin and minus-end directed motor dynein. Many biophysical models have been constructed to understand the mechanism of this motion. However, so far, the basic principle about it remains unclosed. In this paper, based on the recent experimental results and existing theoretical models, a spider-like model is provided. In this model, each motor is regarded as a bead-spring system. The bead can bind to or unbind from the track stochastically, and step forward or backward with fixed step size L and force dependent transition rates. The spring connects the bead to cargo tightly. At any time, the position of cargo is determined by force balance condition. The obvious characteristics of our model are that, the motors interact with each other and they do not share the external load equally. Our results indicate, the stall force of cargo, under which the mean velocity of cargo vanishe...

  15. A Reconsideration of the Link between the Energetics of Water and of ATP Hydrolysis Energy in the Power Strokes of Molecular Motors in Protein Structures

    Directory of Open Access Journals (Sweden)

    Wilfred F. Widdas

    2008-09-01

    Full Text Available Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick’s work, energetics were revised by Joule’s experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration.

  16. GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

    Science.gov (United States)

    Sabharwal, Priyanka; Lee, Changhee; Park, Sungjin; Rao, Meenakshi; Sockanathan, Shanthini

    2011-09-22

    The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors. Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell-autonomous feedback mechanism that directly regulates progenitor cell differentiation, implying that subtype specification initiates within motor neuron progenitor populations prior to their differentiation into postmitotic motor neurons.

  17. Electric motor handbook

    CERN Document Server

    Chalmers, B J

    2013-01-01

    Electric Motor Handbook aims to give practical knowledge in a wide range of capacities such as plant design, equipment specification, commissioning, operation and maintenance. The book covers topics such as the modeling of steady-state motor performance; polyphase induction, synchronous, and a.c. commutator motors; ambient conditions, enclosures, cooling and loss dissipation; and electrical supply systems and motor drives. Also covered are topics such as variable-speed drives and motor control; materials and motor components; insulation types, systems, and techniques; and the installation, sit

  18. UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons.

    Science.gov (United States)

    Edwards, Stacey L; Morrison, Logan M; Yorks, Rosalina M; Hoover, Christopher M; Boominathan, Soorajnath; Miller, Kenneth G

    2015-09-01

    The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16's organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-α). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(-) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADα (a SAD-1-interacting protein) in the CSS system. In an unc-16(-) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(-) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16's organelle transport regulatory function.

  19. The distal hereditary motor neuropathies.

    Science.gov (United States)

    Rossor, Alexander M; Kalmar, Bernadett; Greensmith, Linda; Reilly, Mary M

    2012-01-01

    The distal hereditary motor neuropathies (dHMN) comprise a heterogeneous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT2) and with juvenile forms of amyotrophic lateral sclerosis and hereditary spastic paraplegia. Eleven causative genes and four loci have been identified with autosomal dominant, recessive and X-linked patterns of inheritance. Despite advances in the identification of novel gene mutations, 80% of patients with dHMN have a mutation in an as-yet undiscovered gene. The causative genes have implicated proteins with diverse functions such as protein misfolding (HSPB1, HSPB8, BSCL2), RNA metabolism (IGHMBP2, SETX, GARS), axonal transport (HSPB1, DYNC1H1, DCTN1) and cation-channel dysfunction (ATP7A and TRPV4) in motor-nerve disease. This review will summarise the clinical features of the different subtypes of dHMN to help focus genetic testing for the practising clinician. It will also review the neuroscience that underpins our current understanding of how these mutations lead to a motor-specific neuropathy and highlight potential therapeutic strategies. An understanding of the functional consequences of gene mutations will become increasingly important with the advent of next-generation sequencing and the need to determine the pathogenicity of large amounts of individual genetic data.

  20. Introduction to ultrasonic motors

    Energy Technology Data Exchange (ETDEWEB)

    Sashida, Toshiiku; Kenjo, Takashi.

    1993-01-01

    The ultrasonic motor, invented in 1980, utilizes the piezoelectric effect in the ultrasonic frequency range to provide the motive force. (In conventional electric motors the motive force is electromagnetic.) The result is a motor with unusually good low-speed high-torque and power-to-weight characteristics. It has already found applications in camera autofocus mechanisms, medical equipment subject to high magnetic fields, and motorized car accessories. Its applications will increase as designers become more familiar with its unique characteristics. This book is the result of a collaboration between the inventor and an expert in conventional electric motors: the result is an introduction to the general theory presented in a way that links it to conventional motor theory. It will be invaluable both to motor designers and to those who design with and use electric motors as an introduction to this important new invention.

  1. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  2. Piezoelectric Motors, an Overview

    OpenAIRE

    Karl Spanner; Burhanettin Koc

    2016-01-01

    Piezoelectric motors are used in many industrial and commercial applications. Various piezoelectric motors are available in the market. All of the piezoelectric motors use the inverse piezoelectric effect, where microscopically small oscillatory motions are converted into continuous or stepping rotary or linear motions. Methods of obtaining long moving distance have various drive and functional principles that make these motors categorized into three groups: resonance-drive (piezoelectric ult...

  3. Electric Motor Thermal Management

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-01

    Thermal management enables more efficient and cost-effective motors. This Annual Merit Review presentation describes the technical accomplishments and progress in electric motor thermal management R&D over the last year. This project supports a broad industry demand for data, analysis methods, and experimental techniques to improve and better understand motor thermal management.

  4. Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex.

    Science.gov (United States)

    Popov-Čeleketić, Dušan; Waegemann, Karin; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

    2011-06-01

    The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion.

  5. Towards synthetic molecular motors: a model elastic-network study

    Science.gov (United States)

    Sarkar, Amartya; Flechsig, Holger; Mikhailov, Alexander S.

    2016-04-01

    Protein molecular motors play a fundamental role in biological cells and development of their synthetic counterparts is a major challenge. Here, we show how a model motor system with the operation mechanism resembling that of muscle myosin can be designed at the concept level, without addressing the implementation aspects. The model is constructed as an elastic network, similar to the coarse-grained descriptions used for real proteins. We show by numerical simulations that the designed synthetic motor can operate as a deterministic or Brownian ratchet and that there is a continuous transition between such two regimes. The motor operation under external load, approaching the stall condition, is also analysed.

  6. Validate Mitotic Checkpoint and Kinetochore Motor Proteins in Breast Cancer Cells as Targets for the Development of Novel Anti-Mitotic Drugs

    Science.gov (United States)

    2005-07-01

    of the Human Kinetochore Protein CENP-E Isabel Garcia-Saez’, Tim Yen 2, Richard H. Wade’ and Frank Kozielskil* ’Laboratoire de Microscopic The human...kinetochore is a highly complex macromolecular structure Electronique Structurale that connects chromosomes to spindle microtubules (MTs) in order to

  7. The DNA maturation domain of gpA, the DNA packaging motor protein of bacteriophage lambda, contains an ATPase site associated with endonuclease activity.

    Science.gov (United States)

    Ortega, Marcos E; Gaussier, Hélène; Catalano, Carlos E

    2007-11-02

    Terminase enzymes are common to double-stranded DNA (dsDNA) viruses and are responsible for packaging viral DNA into the confines of an empty capsid shell. In bacteriophage lambda the catalytic terminase subunit is gpA, which is responsible for maturation of the genome end prior to packaging and subsequent translocation of the matured DNA into the capsid. DNA packaging requires an ATPase catalytic site situated in the N terminus of the protein. A second ATPase catalytic site associated with the DNA maturation activities of the protein has been proposed; however, direct demonstration of this putative second site is lacking. Here we describe biochemical studies that define protease-resistant peptides of gpA and expression of these putative domains in Escherichia coli. Biochemical characterization of gpA-DeltaN179, a construct in which the N-terminal 179 residues of gpA have been deleted, indicates that this protein encompasses the DNA maturation domain of gpA. The construct is folded, soluble and possesses an ATP-dependent nuclease activity. Moreover, the construct binds and hydrolyzes ATP despite the fact that the DNA packaging ATPase site in the N terminus of gpA has been deleted. Mutation of lysine 497, which alters the conserved lysine in a predicted Walker A "P-loop" sequence, does not affect ATP binding but severely impairs ATP hydrolysis. Further, this mutation abrogates the ATP-dependent nuclease activity of the protein. These studies provide direct evidence for the elusive nucleotide-binding site in gpA that is directly associated with the DNA maturation activity of the protein. The implications of these results with respect to the two roles of the terminase holoenzyme, DNA maturation and DNA packaging, are discussed.

  8. Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation.

    Science.gov (United States)

    Rioult-Pedotti, Mengia-Seraina; Pekanovic, Ana; Atiemo, Clement Osei; Marshall, John; Luft, Andreas Rüdiger

    2015-01-01

    Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease.

  9. Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation.

    Directory of Open Access Journals (Sweden)

    Mengia-Seraina Rioult-Pedotti

    Full Text Available Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA, leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease.

  10. A Reconfigurable Stepping Motor

    Science.gov (United States)

    Rogers, Charles; Selvaggi, Richard

    2009-04-01

    Multiphase brushless actuators, commonly known as the stepper motors, are ubiquitous for many precision control applications. Developments in the microelectronics have lead to their use as efficient drive motors for modern electric vehicles. Understanding the physics and the control logic for interfacing these transducers continues to be important for scientists and engineers. An overview of the stepping motor principles and interfacing requirements is presented and a simple working model used to teach the concepts of stepper motors is described and demonstrated. This model was used to design a much larger stepper motor required to precisely rotate a massive optical system in the undergraduate advanced physics laboratory.

  11. Induction motor control design

    CERN Document Server

    Marino, Riccardo; Verrelli, Cristiano M

    2010-01-01

    ""Nonlinear and Adaptive Control Design for Induction Motors"" is a unified exposition of the most important steps and concerns in the design of estimation and control algorithms for induction motors. A single notation and modern nonlinear control terminology is used to make the book accessible to readers who are not experts in electric motors at the same time as giving a more theoretical control viewpoint to those who are. In order to increase readability, the book concentrates on the induction motor, eschewing the much more complex and less-well-understood control of asynchronous motors. The

  12. Solid propellant motor

    Science.gov (United States)

    Shafer, J. I.; Marsh, H. E., Jr. (Inventor)

    1978-01-01

    A case bonded end burning solid propellant rocket motor is described. A propellant with sufficiently low modulus to avoid chamber buckling on cooling from cure and sufficiently high elongation to sustain the stresses induced without cracking is used. The propellant is zone cured within the motor case at high pressures equal to or approaching the pressure at which the motor will operate during combustion. A solid propellant motor with a burning time long enough that its spacecraft would be limited to a maximum acceleration of less than 1 g is provided by one version of the case bonded end burning solid propellant motor of the invention.

  13. Motor/generator

    Science.gov (United States)

    Hickam, Christopher Dale

    2008-05-13

    A motor/generator is provided for connecting between a transmission input shaft and an output shaft of a prime mover. The motor/generator may include a motor/generator housing, a stator mounted to the motor/generator housing, a rotor mounted at least partially within the motor/generator housing and rotatable about a rotor rotation axis, and a transmission-shaft coupler drivingly coupled to the rotor. The transmission-shaft coupler may include a clamp, which may include a base attached to the rotor and a plurality of adjustable jaws.

  14. Effects of a High Protein Food Supplement on Physical Activity, Motor Performance and Health Related Quality of Life of HIV Infected Botswana Children on Anti-Retroviral Therapy (ART

    Directory of Open Access Journals (Sweden)

    Leapetswe Malete

    2017-05-01

    Full Text Available Objective: Despite existing evidence about the benefits of nutrition, physical activity (PA and sport to the overall health and wellbeing of children, knowledge gaps remain on this relationship in children living with chronic conditions like HIV/AIDS. Such knowledge should inform context specific programs that could enhance the quality of life of children. The purpose of this study was to examine the effects of integrating a nutrition intervention (culturally tailored food supplement into antiretroviral therapy (ART on psychosocial outcomes and physical activity among HIV-positive children in Botswana. Method: 201 HIV-positive children (6–15 years; M = 9.44, SD = 2.40 were recruited and randomly assigned (stratified by age and gender to two groups. The intervention group (n = 97 received a high protein (bean-sorghum plus micronutrients food supplement, while the control group (n = 104 received a sorghum plus micronutrients supplement. Participants were followed over 12 months. Anthropometric measures, PA, motor performance, and health related quality of life (HRQL were collected at baseline, 6 and 12 months. Results: Mixed repeated-measures ANOVA revealed a significant time effect of the food supplement on target variables except body fat percentage, speed, and school functioning. Time×treatment interaction was found for physical functioning, psyioning achosocial functnd total quality of life score. Scores on physical functioning and total of quality life in the intervention group significantly increased from baseline to 6 months compared with the control group (p = 0.015. Conclusion: A combination of ART and nutritional intervention had a positive effect on physical functioning and total quality of life of HIV-positive children in this study. There were also improvements to physical activity and motor performance tests over time. More research is needed on long term effects of nutrition and PA interventions on HRQL in children living with

  15. Motor degradation prediction methods

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, J.R.; Kelly, J.F.; Delzingaro, M.J.

    1996-12-01

    Motor Operated Valve (MOV) squirrel cage AC motor rotors are susceptible to degradation under certain conditions. Premature failure can result due to high humidity/temperature environments, high running load conditions, extended periods at locked rotor conditions (i.e. > 15 seconds) or exceeding the motor`s duty cycle by frequent starts or multiple valve stroking. Exposure to high heat and moisture due to packing leaks, pressure seal ring leakage or other causes can significantly accelerate the degradation. ComEd and Liberty Technologies have worked together to provide and validate a non-intrusive method using motor power diagnostics to evaluate MOV rotor condition and predict failure. These techniques have provided a quick, low radiation dose method to evaluate inaccessible motors, identify degradation and allow scheduled replacement of motors prior to catastrophic failures.

  16. Neuroplasticity & Motor Learning

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye

    Practice of a new motor task is usually associated with an improvement in performance. Indeed, if we stop practicing and return the next day to the same task, we find that our performance has been maintained and may even be better than it was at the start of the first day. This improvement...... is a measure of our ability to form and store a motor memory of the task. However, the initial memory of the task is labile and may be subject to interference. During and following motor learning plastic changes occur within the central nervous system. On one hand these changes are driven by motor practice......, on the other hand the changes underlie the formation of motor memory and the retention of improved motor performance. During motor learning changes may occur at many different levels within the central nervous system dependent on the type of task and training. Here, we demonstrate different studies from our...

  17. Piezoelectric Motors, an Overview

    Directory of Open Access Journals (Sweden)

    Karl Spanner

    2016-02-01

    Full Text Available Piezoelectric motors are used in many industrial and commercial applications. Various piezoelectric motors are available in the market. All of the piezoelectric motors use the inverse piezoelectric effect, where microscopically small oscillatory motions are converted into continuous or stepping rotary or linear motions. Methods of obtaining long moving distance have various drive and functional principles that make these motors categorized into three groups: resonance-drive (piezoelectric ultrasonic motors, inertia-drive, and piezo-walk-drive. In this review, a comprehensive summary of piezoelectric motors, with their classification from initial idea to recent progress, is presented. This review also includes some of the industrial and commercial applications of piezoelectric motors that are presently available in the market as actuators.

  18. Monte Carlo simulations of single and coupled synthetic molecular motors.

    Science.gov (United States)

    Chen, C-M; Zuckermann, M

    2012-11-01

    We use a minimal model to study the processive motion of coupled synthetic molecular motors along a DNA track and we present data from Monte Carlo (MC) computer simulations based on this model. The model was originally proposed by Bromley et al. [HFSP J. 3, 204 (2009)] for studying the properties of a synthetic protein motor, the "Tumbleweed" (TW), and involves rigid Y-shaped motors diffusively rotating along the track while controlled by a series of periodically injected ligand pulses into the solution. The advantage of the model is that it mimics the mechanical properties of the TW motor in detail. Both the average first passage time which measures the diffusive motion of the motors, and the average dwell time on the track which measures their processivity are investigated by varying the parameters of the model. The latter includes ligand concentration and the range and strength of the binding interaction between motors and the track. In particular, it is of experimental interest to study the dependence of these dynamic time scales of the motors on the ligand concentration. Single rigid TW motors were first studied since no previous MC simulations of these motors have been performed. We first studied single motors for which we found a logarithmic decrease of the average first passage time and a logarithmic increase of the average dwell time with increasing ligand concentration. For two coupled motors, the dependence on ligand concentration is still logarithmic for the average first passage time but becomes linear for the average dwell time. This suggests a much greater stability in the processive motion of coupled motors as compared to single motors in the limit of large ligand concentration. By increasing the number of coupled motors, m, it was found that the average first passage time of the coupled motors only increases slowly with m while the average dwell time increases exponentially with m. Thus the stability of coupled motors on the track can be

  19. Aging, Alzheimer’s, and APOE genotype influence the expression and neuronal distribution patterns of microtubule motor protein dynactin-P50

    Directory of Open Access Journals (Sweden)

    Orwa eAboud

    2015-03-01

    Full Text Available Reports from neural cell cultures and experimental animal studies provide evidence of age- and disease-related changes in retrograde transport of spent or misfolded proteins destined for degradation or recycling. However, few studies address these issues in human brain from those who either age without dementia and overt neuropathology, or succumb to Alzheimer’s; especially as such propensity may be influenced by APOE genotype. We studied the expression and distribution of the dynein subunit dynactin-P50, the β amyloid precursor protein (βAPP, and hyperphosphorylated tau (P-tau in tissues and tissue sections of brains from non-demented, neuropathology-free patients and from Alzheimer patients, with either APOE ε3,3 or APOE ε4,4. We found that advanced age in patients without dementia or neuropathological change was associated with coordinated increases in dynactin-P50 and βAPP in neurons in pyramidal layers of the hippocampus. In contrast, in Alzheimer’s, βAPP and dynactin were significantly reduced. Furthermore, the dynactin-P50 and βAPP that was present was located primarily in dystrophic neurites in Aβ plaques. Tissues from Alzheimer patients with APOE ε3,3 had less P-tau, more βAPP, dynactin-P50, and synaptophysin than did tissues from Alzheimer patients carrying APOE ε4,4. It is logical to conclude, then, that as neurons age successfully, there is coordination between retrograde delivery and maintenance and repair, as well as between retrograde delivery and degradation and/or recycling of spent proteins. The buildup of proteins slated for repair, synaptic viability, transport, and re-cycling in neuron soma and dystrophic neurites suggest a loss of this coordination in Alzheimer neurons. Inheritance of APOE ε3,3 rather than APOE ε4,4, is associated with neuronal resilience, suggestive of better repair capabilities, more synapses, more efficient transport, and less hyperphosphorylation of tau. We conclude that even in disease

  20. Crowding of molecular motors determines microtubule depolymerization

    CERN Document Server

    Reese, Louis; Frey, Erwin

    2011-01-01

    Assembly and disassembly dynamics of microtubules (MTs) is tightly controlled by MT associated proteins. Here, we investigate how plus-end-directed depolymerases of the kinesin-8 family regulate MT depolymerization dynamics. Employing an individual-based model, we reproduce experimental findings. Moreover, crowding is identified as the key regulatory mechanism of depolymerization dynamics. Our analysis gives two qualitatively distinct regimes. For motor densities above a particular threshold, a macroscopic traffic jam emerges at the plus-end and the MT dynamics become independent of the motor concentration. Below this threshold, microscopic traffic jams at the tip arise which cancel out the effect of the depolymerization kinetics such that the depolymerization speed is solely determined by the motor density. Because this density changes over the MT length, length-dependent regulation is possible. Remarkably, motor cooperativity does not affect the depolymerization speed but only the end-residence time of depo...

  1. Microtubule length dependence of motor traffic in cells.

    Science.gov (United States)

    Zhang, Yunxin

    2012-10-01

    Motor proteins in living cells, such as kinesin and dynein, can move processively along the microtubule (MT), and can also detach from or attach to MT stochastically. Experiments found that the traffic of motors along MT may be jammed; thus various theoretical models were designed to understand this process. However, previous studies mainly focused on motor attachment/detachment rate dependent properties. Leduc et al. recently found that the traffic jam of motor protein Kip3 depends on MT length (Proc. Natl. Acad. Sci. U.S.A. 109, 6100 (2012)). Therefore, this study discusses the MT length-dependent properties of motor traffic. The results showed that MT length has one critical value N(c); a traffic jam occurs only when MT length N > N(c). The jammed MT length increases with total MT length N , whereas the non-jammed MT length may not change monotonically with N . The critical value N(c) increases with motor detachment rate from MT, but decreases with motor attachment rate to MT. Therefore, the traffic of motors will be more likely to be jammed when the MT is long, motor detachment rate is high, and motor detachment rate is low.

  2. Modularity for Motor Control and Motor Learning.

    Science.gov (United States)

    d'Avella, Andrea

    2016-01-01

    How the central nervous system (CNS) overcomes the complexity of multi-joint and multi-muscle control and how it acquires or adapts motor skills are fundamental and open questions in neuroscience. A modular architecture may simplify control by embedding features of both the dynamic behavior of the musculoskeletal system and of the task into a small number of modules and by directly mapping task goals into module combination parameters. Several studies of the electromyographic (EMG) activity recorded from many muscles during the performance of different tasks have shown that motor commands are generated by the combination of a small number of muscle synergies, coordinated recruitment of groups of muscles with specific amplitude balances or activation waveforms, thus supporting a modular organization of motor control. Modularity may also help understanding motor learning. In a modular architecture, acquisition of a new motor skill or adaptation of an existing skill after a perturbation may occur at the level of modules or at the level of module combinations. As learning or adapting an existing skill through recombination of modules is likely faster than learning or adapting a skill by acquiring new modules, compatibility with the modules predicts learning difficulty. A recent study in which human subjects used myoelectric control to move a mass in a virtual environment has tested this prediction. By altering the mapping between recorded muscle activity and simulated force applied on the mass, as in a complex surgical rearrangement of the tendons, it has been possible to show that it is easier to adapt to a perturbation that is compatible with the muscle synergies used to generate hand force than to a similar but incompatible perturbation. This result provides direct support for a modular organization of motor control and motor learning.

  3. Dendrite-derived supernumerary axons on adult axotomized motor neurons possess proteins that are essential for the initiation and propagation of action potentials and synaptic vesicle release

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; MacDermid, Victoria E; Montague, Steven J

    2011-01-01

    on these processes matches the arrangement of these channels that is necessary for the initiation and conduction of action potentials. At terminal bouton-like structures they possess key proteins necessary for the release of synaptic vesicles (SV2 and synaptophysin). Thus, axon-like processes emanating from the tips......Axotomy can trigger profound alterations in the neuronal polarity of adult neurons in vivo. This can manifest itself in the development of new axon-like processes emanating from the tips of distal dendrites. Previously, these processes have been defined as axonal based on their axonal morphology....... This study extends this definition to determine whether, more importantly, these processes possess the prerequisite molecular machinery to function as axons. Using a combination of intracellular labeling and immunohistochemistry, we demonstrate that the distribution of voltage-gated sodium channels...

  4. Force-activated substrates for high-precision, high-throughput optical trapping assays of ssDNA motor proteins (Conference Presentation)

    Science.gov (United States)

    Okoniewski, Stephen; Perkins, Thomas T.

    2016-09-01

    Optical-trapping-based assays can measure individual proteins bind to and move along DNA with sub-nm resolution, and have yielded insight into a broad array of protein-DNA interactions. Unfortunately, collecting large numbers of high-resolution traces remains an ongoing challenge. Studying helicase motion along DNA exemplifies this challenge. One major difficulty is that helicase binding often requires a single stranded (ss)-double stranded (ds) DNA junction flanked by ssDNA with a minimum size and orientation. Historically, creating such DNA substrates is inefficient. More problematic is that data throughput is low in standard surface-based assays since all substrates are unwound upon introduction of ATP. The net result is 2-4 high-resolution traces on a good day. To improve throughput, we sought to turn-on or activate a substrate for a helicase one molecule at a time and thereby sequentially study many molecules on an individual microscope slide. As a first step towards this goal, we engineered a dsDNA that contains two site-specific nicks along the same strand of the dsDNA but no ssDNA. Upon overstretching the DNA (F = 65 pN), the strand between the two nicks was mechanically dissociated. We demonstrated this with two different substrates: one yielding an internal ssDNA region of 1100 nt and the other yielding a 20-bp long hairpin flanked by 30 nt of ssDNA. Unwinding a hairpin yields a 3-fold larger signal while the 30-nt ssDNA serves as the binding site for the helicase. We expect that these force-activated substrates to significantly accelerate high-resolution optical-trapping studies of DNA helicases.

  5. ELECTRIC MOTOR CARS.

    Science.gov (United States)

    PASSENGER VEHICLES , ELECTRIC MOTORS), FEASIBILITY STUDIES, BATTERY COMPONENTS, ELECTRIC BATTERIES, FUEL CELLS, ENERGY CONVERSION, NUCLEAR ENERGY, THERMIONIC CONVERTERS , THERMOELECTRICITY, POWER EQUIPMENT, COSTS

  6. The bacteriophage DNA packaging motor.

    Science.gov (United States)

    Rao, Venigalla B; Feiss, Michael

    2008-01-01

    An ATP-powered DNA translocation machine encapsidates the viral genome in the large dsDNA bacteriophages. The essential components include the empty shell, prohead, and the packaging enzyme, terminase. During translocation, terminase is docked on the prohead's portal protein. The translocation ATPase and the concatemer-cutting endonuclease reside in terminase. Remarkably, terminases, portal proteins, and shells of tailed bacteriophages and herpes viruses show conserved features. These DNA viruses may have descended from a common ancestor. Terminase's ATPase consists of a classic nucleotide binding fold, most closely resembling that of monomeric helicases. Intriguing models have been proposed for the mechanism of dsDNA translocation, invoking ATP hydrolysis-driven conformational changes of portal or terminase powering DNA motion. Single-molecule studies show that the packaging motor is fast and powerful. Recent advances permit experiments that can critically test the packaging models. The viral genome translocation mechanism is of general interest, given the parallels between terminases, helicases, and other motor proteins.

  7. Scale dependence of mechanics and dynamics of active gels with increasing motor concentration

    CERN Document Server

    Sonn-Segev, Adar; Roichman, Yael

    2016-01-01

    The cytoskeleton protein actin assembles into large bundles when supporting stresses in the cell, but grows into a fine branched network to induce cell motion. Such self-organization processes are studied in artificial networks of cytoskeleton proteins with thick actin bundles and large motor protein aggregates to enable optical observation. The effect of motor aggregate size on the cytoskeleton mechanical properties is studied here in networks comprised of much smaller motor assemblies. Large motor protein clusters are known to increase the stiffness of actin based networks by introducing tension and additional cross-linking cites. We find that these effects are universal to actin gels regardless of actin bundle thickness and motor aggregate size and are relevant, therefore, to a wide range of cytoskeleton based cellular processes. In contrast, motor induced active fluctuations depend significantly on motor assembly size, featuring unique non-Gaussian statistics at high concentrations of small assemblies.

  8. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system...

  9. To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

    NARCIS (Netherlands)

    Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Prekoracka-Krawczyk, Anna; Jaskowski, Wojciech; van der Lubbe, Robert Henricus Johannes

    2016-01-01

    Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and

  10. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  11. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    1990-01-01

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  12. MISR Motor Data V003

    Data.gov (United States)

    National Aeronautics and Space Administration — This file contains the output for the Level 1A Motor data (Suggested Usage: MISR SCF processing needs the MISR motor data samples for the analysis of motor anomalies...

  13. Bicaudal-D: Switching motors, cargo and direction

    NARCIS (Netherlands)

    G.D. Splinter (Daniël)

    2008-01-01

    textabstractScope of this thesis Transport of vesicles and organelles is an essential cellular process. Proteins like Rab GTPases, specialized adaptor proteins and motor proteins are involved in targeting and movement of cargos to their destination. This thesis describes the function of the mammalia

  14. High-Pressure Microscopy for Studying Molecular Motors.

    Science.gov (United States)

    Nishiyama, Masayoshi

    2015-01-01

    Movement is a fundamental characteristic of all living things. This biogenic function is carried out by various nanometer-sized molecular machines. Molecular motor is a typical molecular machinery in which the characteristic features of proteins are integrated; these include enzymatic activity, energy conversion, molecular recognition and self-assembly. These biologically important reactions occur with the association of water molecules that surround the motors. Applied pressures can alter the intermolecular interactions between the motors and water. In this chapter we describe the development of a high-pressure microscope and a new motility assay that enables the visualization of the motility of molecular motors under conditions of high-pressure. Our results demonstrate that applied pressure dynamically changes the motility of molecular motors such as kinesin, F1-ATPase and bacterial flagellar motors.

  15. Engineering Nanoscale Biological Molecular Motors

    OpenAIRE

    Korosec, Chapin; Forde, Nancy R.

    2017-01-01

    Understanding the operation of biological molecular motors, nanoscale machines that transduce electrochemical energy into mechanical work, is enhanced by bottom-up strategies to synthesize novel motors.

  16. Improve Motor System Efficiency for a Broad Range of Motors with MotorMaster+ International

    Energy Technology Data Exchange (ETDEWEB)

    None

    2005-05-01

    Available at no charge, MotorMaster+ International is designed to support motor systems improvement planning at industrial facilities by identifying the most cost-effective choice when deciding to repair or replace older motor models.

  17. Protein kinase C inhibitor improves motor complications in a rat model of Parkinson's disease%蛋白激酶C抑制剂改善帕金森病大鼠异动症的研究

    Institute of Scientific and Technical Information of China (English)

    孔敏; 宋璐; 巴茂文; 刘振国

    2010-01-01

    Objective To investigate the cytological and behavioral effects of protein kinase C (PKC) inhibitor tamoxifen on levodopa-induced motor complications of a rat model. Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-hydroxydopamine (6-OHDA) into right medial forebrain bundle (MFB). Two sets of experiments were performed. First, rats were intraperitoneally treated with 50 mg/kg levodopa plus 12.5 mg/kg henserazide, twice daily for 22 days. On day 23, the rats received either tamoxifen or vehicle before levodopa administration. Rotational duration and peak rotation were estimated. After being sacrificed, subcellular distribution and phosphorylation (S890 and S896) of N-methyl-D-aspartate receptor subunit 1 (NR1) were observed by Western blot. Results Our study showed that tamoxifen reduced peak rotation [(121.0±7.6) times vs. (161.55±22.1) times, t=2.6, P<0.05]. Moreover, tamoxifen could regulate subcellular distribution of NR1 which was closely associated with levodopa-induced motor complications, reduce the expression of NR1 in the membrane protein as compared with levodopa+ vehicle group [(82.4%±5.1%) vs. (103.0%±3.5%), t= 6.7, P<0.05], and reduce the phosphorylation of NR1S890 (77.2%±4.2%) and NR1S896 (98.4%±6. 4%), respectively (t= 5.9,3.6,both P<0.05). Conclusions These results indicate that chronic levodopa treatment activates serine kinase and leads to phosphorylation of glutamate receptors, and thus contributes to development of motor complications. Pharmaceuticals which inhibit serine kinase, such as PKC, may be useful in the treatment and prevention of motor complications in parkinsonian patients.%目的 探讨蛋白激酶C(PKC)抑制剂他莫昔芬对左旋多巴诱发异动症的细胞学与行为学效应. 方法将6-羟多巴胺立体定向注射于大鼠前脑内侧束建立帕金森病(PD)动物模型.模型成功的PD大鼠接受每天2次左旋多巴(50 mg/kg左旋多巴+12.5 mg

  18. PTPRR, cerebellum, and motor coordination.

    Science.gov (United States)

    Schmitt, Ina; Bitoun, Emmanuelle; Manto, Mario

    2009-06-01

    Tyrosine phosphorylation is a powerful mechanism of modulation for proliferation, differentiation, and functioning of neurons. The protein products of the neuronal mouse gene PTPRR are physiological regulators of mitogen-activated protein kinase (MAPK) activities. PTPRR(-/-) mice display deficits of motor coordination and balance skills. PTPRR gene orthologues are found in many vertebrates. Recent observations suggest that the human episodic ataxia 2 (EA2) and spinocerebellar ataxia types 6 (SCA6), 12 (SCA12), and 14 (SCA14) might be associated with impaired phosphorylation levels of cerebellum calcium channels and receptors. The concept that MAPK signaling is a key process in tuning synaptic plasticity in cerebellar circuits is now emerging, with numerous implications for understanding cerebellar functions and cerebellar disorders.

  19. Mechanism of Processive Movement of Monomeric and Dimeric Kinesin Molecules

    Directory of Open Access Journals (Sweden)

    Ping Xie

    2010-01-01

    Full Text Available Kinesin molecules are motor proteins capable of moving along microtubule by hydrolyzing ATP. They generally have several forms of construct. This review focuses on two of the most studied forms: monomers such as KIF1A (kinesin-3 family and dimers such as conventional kinesin (kinesin-1 family, both of which can move processively towards the microtubule plus end. There now exist numerous models that try to explain how the kinesin molecules convert the chemical energy of ATP hydrolysis into the mechanical energy to “power” their proceesive movement along microtubule. Here, we attempt to present a comprehensive review of these models. We further propose a new hybrid model for the dimeric kinesin by combining the existing models and provide a framework for future studies in this subject.

  20. General Motors Goes Metric

    Science.gov (United States)

    Webb, Ted

    1976-01-01

    Describes the program to convert to the metric system all of General Motors Corporation products. Steps include establishing policy regarding employee-owned tools, setting up training plans, and making arrangements with suppliers. (MF)

  1. Piezoelectric Rotary Tube Motor

    Science.gov (United States)

    Fisher, Charles D.; Badescu, Mircea; Braun, David F.; Culhane, Robert

    2011-01-01

    A custom rotary SQUIGGLE(Registered TradeMark) motor has been developed that sets new benchmarks for small motor size, high position resolution, and high torque without gear reduction. Its capabilities cannot be achieved with conventional electromagnetic motors. It consists of piezoelectric plates mounted on a square flexible tube. The plates are actuated via voltage waveforms 90 out of phase at the resonant frequency of the device to create rotary motion. The motors were incorporated into a two-axis postioner that was designed for fiber-fed spectroscopy for ground-based and space-based projects. The positioner enables large-scale celestial object surveys to take place in a practical amount of time.

  2. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...

  3. Congenital Ocular Motor Apraxia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-06-01

    Full Text Available The clinical and neuroradiological findings, and long-term intellectual prognosis in 10 patients (4 boys and 6 girls with congenital ocular motor apraxia (COMA are reviewed by researchers at Tottori University, Yonago, Japan.

  4. Motor Carrier Crash Data -

    Data.gov (United States)

    Department of Transportation — Contains data on large trucks and buses involved in Federally reportable crashes as per Title 49 U.S.C. Part 390.5 (crashes involving a commercial motor vehicle, and...

  5. Split-phase motor running as capacitor starts motor and as capacitor run motor

    Directory of Open Access Journals (Sweden)

    Yahaya Asizehi ENESI

    2016-07-01

    Full Text Available In this paper, the input parameters of a single phase split-phase induction motor is taken to investigate and to study the output performance characteristics of capacitor start and capacitor run induction motor. The value of these input parameters are used in the design characteristics of capacitor run and capacitor start motor with each motor connected to rated or standard capacitor in series with auxiliary winding or starting winding respectively for the normal operational condition. The magnitude of capacitor that will develop maximum torque in capacitor start motor and capacitor run motor are investigated and determined by simulation. Each of these capacitors is connected to the auxiliary winding of split-phase motor thereby transforming it into capacitor start or capacitor run motor. The starting current and starting torque of the split-phase motor (SPM, capacitor run motor (CRM and capacitor star motor (CSM are compared for their suitability in their operational performance and applications.

  6. A Stochastic Markov Model for Coordinated Molecular Motors

    CERN Document Server

    Materassi, Donatello; Salapaka, Murti V

    2010-01-01

    Many cell functions are accomplished thanks to intracellular transport mechanisms of macromolecules along filaments. Molecular motors such as dynein or kinesin are proteins playing a primary role in these processes. The behavior of such proteins is quite well understood when there is only one of them moving a cargo particle. Indeed, numerous in vitro experiments have been performed to derive accurate models for a single molecular motor. However, in vivo macromolecules are often carried by multiple motors. The main focus of this paper is to provide an analysis of the behavior of more molecular motors interacting together in order to improve the understanding of their actual physiological behavior. Previous studies provide analyses based on results obtained from Monte Carlo simulations. Different from these studies, we derive an equipollent probabilistic model to describe the dynamics of multiple proteins coupled together and provide an exact theoretical analysis. We are capable of obtaining the probability den...

  7. Knowledge and motor performance.

    Science.gov (United States)

    Kerr, R; Boucher, J L

    1992-06-01

    Traditionally, motor skill acquisition has implied that the performance of a given individual on a particular skill is dependent on the amount of prior practice of that skill. However, concepts such as schema theory, or kinetic formulae, or the strategic allocation of resources imply that, even when practising specific skills, performers gain knowledge about their own motor performance which can be used or applied to related or novel situations. An attempt was made to relate the performance of a complex psychomotor task to differing levels of motor skill expertise or knowledge (athlete and nonathlete). 20 subjects performed (1600 responses) on a novel pursuit or tracking task. Analysis indicated that the athletes performed significantly better. Their main advantage appeared to be more in their ability to control and produce fast, accurate movements than in their decision-making. Accepting Henry and Rogers' 1960 proposition that there is no such thing as a general motor ability or coordination factor does not imply that the only alternative is for all motor skills to be specific. It is argued that the differences in the present study arose from the athletes' greater knowledge (schema, kinetic formulae) related to their understanding of their own motor capabilities.

  8. Shape memory alloy based motor

    Indian Academy of Sciences (India)

    S V Sharma; M M Nayak; N S Dinesh

    2008-10-01

    Design and characterization of a new shape memory alloy wire based Poly Phase Motor has been reported in this paper. The motor can be used either in stepping mode or in servo mode of operation. Each phase of the motor consists of an SMA wire with a spring in series. The principle of operation of the poly phase motor is presented. The motor resembles a stepper motor in its functioning though the actuation principles are different and hence has been characterized similar to a stepper motor. The motor can be actuated in either direction with different phase sequencing methods, which are presented in this work. The motor is modelled and simulated and the results of simulations and experiments are presented. The experimental model of the motor is of dimension 150 mm square, 20 mm thick and uses SMA wire of 0·4 mm diameter and 125 mm of length in each phase.

  9. Sensing with the Motor Cortex

    OpenAIRE

    Hatsopoulos, Nicholas G.; Suminski, Aaron J.

    2011-01-01

    The primary motor cortex is a critical node in the network of brain regions responsible for voluntary motor behavior. It has been less appreciated, however, that the motor cortex exhibits sensory responses in a variety of modalities including vision and somatosensation. We review current work that emphasizes the heterogeneity in sensori-motor responses in the motor cortex and focus on its implications for cortical control of movement as well as for brain-machine interface development.

  10. Embedding dual function into molecular motors through collective motion.

    Science.gov (United States)

    Saito, Nen; Kaneko, Kunihiko

    2017-03-10

    Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently.

  11. Cooperative behavior of molecular motors: Cargo transport and traffic phenomena

    Science.gov (United States)

    Lipowsky, Reinhard; Beeg, Janina; Dimova, Rumiana; Klumpp, Stefan; Müller, Melanie J. I.

    2010-01-01

    All eukaryotic cells including those of our own body contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and make discrete mechanical steps with a step size of the order of 10 nm but are able to pull cargo particles over much larger distances, from micrometers up to meters. In vivo, the intracellular cargos include large membrane-bounded organelles, smaller vesicles, a subset of mRNAs, cytoskeletal filaments, and various protein building blocks, which are transported between different cell compartments. This cargo transport is usually performed by teams of motors. If all motors belong to the same molecular species, the cooperative action of the motors leads to uni-directional transport with a strongly increased run length and with a characteristic force dependence of the velocity distributions. If two antagonistic teams of motors pull on the same cargo particle, they perform a stochastic tug-of-war, which is characterized by a subtle force balance between the two motor teams and leads to several distinct patterns of bi-directional transport. So far, all experimental observations on bi-directional transport are consistent with such a tug-of-war. If many motors and/or cargo particles are transported along the filaments, one encounters various traffic phenomena. Depending on their mutual interactions and the compartment geometry, the motors form various spatio-temporal patterns such as traffic jams, and undergo nonequilibrium phase transitions between different patterns of transport.

  12. Advances in motor neurone disease.

    Science.gov (United States)

    Bäumer, Dirk; Talbot, Kevin; Turner, Martin R

    2014-01-01

    Motor neurone disease (MND), the commonest clinical presentation of which is amyotrophic lateral sclerosis (ALS), is regarded as the most devastating of adult-onset neurodegenerative disorders. The last decade has seen major improvements in patient care, but also rapid scientific advances, so that rational therapies based on key pathogenic mechanisms now seem plausible. ALS is strikingly heterogeneous in both its presentation, with an average one-year delay from first symptoms to diagnosis, and subsequent rate of clinical progression. Although half of patients succumb within 3-4 years of symptom onset, typically through respiratory failure, a significant minority survives into a second decade. Although an apparently sporadic disorder for most patients, without clear environmental triggers, recent genetic studies have identified disease-causing mutations in genes in several seemingly disparate functional pathways, so that motor neuron degeneration may need to be understood as a common final pathway with a number of upstream causes. This apparent aetiological and clinical heterogeneity suggests that therapeutic studies should include detailed biomarker profiling, and consider genetic as well as clinical stratification. The most common mutation, accounting for 10% of all Western hemisphere ALS, is a hexanucleotide repeat expansion in C9orf72. This and several other genes implicate altered RNA processing and protein degradation pathways in the core of ALS pathogenesis. A major gap remains in understanding how such fundamental processes appear to function without obvious deficit in the decades prior to symptom emergence, and the study of pre-symptomatic gene carriers is an important new initiative.

  13. Magnetostrictive direct drive motor

    Science.gov (United States)

    Naik, Dipak; Dehoff, P. H.

    1991-01-01

    Highly magnetostrictive materials such as Tb.3Dy.7Fe2, commercially known as TERFENOL-D, have been used to date in a variety of devices such as high power actuators and linear motors. The larger magnetostriction available in twinned single crystal TERFENOL-D, approx. 2000 ppm at moderate magnetic field strengths, makes possible a new generation of magnetomechanical devices. NASA researchers are studying the potential of this material as the basis for a direct microstepping rotary motor with torque densities on the order of industrial hydraulics and five times greater than that of the most efficient, high power electric motors. Such a motor would be a micro-radian stepper, capable of precision movements and self-braking in the power-off state. Innovative mechanical engineering techniques are juxtaposed on proper magnetic circuit design to reduce losses in structural flexures, inertias, thermal expansions, eddy currents, and magneto-mechanical coupling, thus optimizing motor performance and efficiency. Mathematical models are presented, including magnetic, structural, and both linear and nonlinear dynamic calculations and simulations. In addition, test results on prototypes are presented.

  14. Energetics and efficiency of a molecular motor model

    DEFF Research Database (Denmark)

    C. Fogedby, Hans; Svane, Axel

    2013-01-01

    The energetics and efficiency of a linear molecular motor model proposed by Mogilner et al. (Phys. Lett. 237, 297 (1998)) is analyzed from an analytical point of view. The model which is based on protein friction with a track is described by coupled Langevin equations for the motion in combination...... with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor is addressed using a many body scheme with focus on the efficiency at maximum power (EMP). It is found that the EMP is reduced from about 10 pct in a heuristic description of the motor to about 1 per mille...... when incorporating the full motor dynamics, owing to the strong dissipation associated with the motor action....

  15. Biasing the random walk of a molecular motor

    Energy Technology Data Exchange (ETDEWEB)

    Astumian, R Dean [Department of Physics, University of Maine, Orono, ME 04469-5709 (United States)

    2005-11-30

    Biomolecular motors are often described in mechanical terms, with analogy to cars, turbines, judo throws, levers, etc. It is important to remember however that because of their small size, and because of the aqueous environment in which molecular motors move, viscous drag and thermal noise dominate the inertial forces that drive macroscopic machines. The sequence of motions-conformational changes-by which a motor protein moves can best be described as a random walk, with transitions from one state to another occurring by thermal activation over energy barriers. In this paper I will address the question of how this random walk is biased by a non-equilibrium chemical reaction (ATP hydrolysis) so that the motor molecule moves preferentially (with almost unit certainty) in one direction, even when an external force is applied to drive it in the opposite direction. I will also discuss how these 'soft matter' motors can achieve thermodynamic efficiencies of nearly 100%.

  16. Bidirectionality From Cargo Thermal Fluctuations in Motor-Mediated Transport

    CERN Document Server

    Miles, Christopher E

    2016-01-01

    Molecular motor proteins serve as an essential component of intracellular transport by generating forces to haul cargoes along cytoskeletal filaments. In some circumstances, two species of motors that are directed oppositely (e.g. kinesin, dynein) can be attached to the same cargo. The resulting net motion is known to be bidirectional, but the mechanism of switching remains unclear. In this work, we propose a mean-field mathematical model of the mechanical interactions of two populations of molecular motors with diffusion of the cargo (thermal fluctuations) as the fundamental noise source. By studying a simplified model, the delayed response of motors to rapid fluctuations in the cargo is quantified, allowing for the reduction of the full model to two "characteristic positions" of each of the motor populations. The system is then found to be "metastable", switching between two distinct directional transport states, or bidirectional motion. The time to switch between these states is then investigated using WKB...

  17. Advanced AC Motor Control

    Energy Technology Data Exchange (ETDEWEB)

    Kazmierkowski, M.P. [Institute of Control and Industrial Electronics, Warsaw University of Technology, Warszawa (Poland)

    1997-12-31

    In this paper a review of control methods for high performance PWM inverter-fed induction motor drives is presented. Starting from the description of an induction motor by the help of the space vectors, three basic control strategic are discussed. As first, the most popular Field Oriented Control (FOC) is described. Secondly, the Direct Torque and Flux vector Control (DTFC) method, which - in contrast to FOC - depart from idea of coordinate transformation and analogy with DC motor, is briefly characterized. The last group is based on Feedback Linearization Control (FLC) and can be easy combined with sliding mode control. The simulation and experimental oscillograms that illustrate the performance of the discussed control strategies are shown. (orig.) 35 refs.

  18. Mechanical design of electric motors

    CERN Document Server

    Tong, Wei

    2014-01-01

    Rapid increases in energy consumption and emphasis on environmental protection have posed challenges for the motor industry, as has the design and manufacture of highly efficient, reliable, cost-effective, energy-saving, quiet, precisely controlled, and long-lasting electric motors.Suitable for motor designers, engineers, and manufacturers, as well as maintenance personnel, undergraduate and graduate students, and academic researchers, Mechanical Design of Electric Motors provides in-depth knowledge of state-of-the-art design methods and developments of electric motors. From motor classificati

  19. Induction motor starting current

    Energy Technology Data Exchange (ETDEWEB)

    Arneaud, J.M.; Langman, R.A. [Tasmania Univ., Hobart, TAS (Australia)

    1995-12-31

    Large errors may occur if leakage path saturation is neglected when reduced-voltage test results are used to predict the direct-on-line starting current of induction motors. The results of applying three existing and two new methods for starting current prediction are compared with test data from 52 motors. A quantitative assessment is made of the probable reduction in error that would be achieved by increasing the number of available sets of reduced-voltage, locked rotor test results or by including slot design data. Guidelines are given for selecting an appropriate predictive method. (author). 4 tabs., 1 fig., 6 refs.

  20. Step Motor Control System

    Institute of Scientific and Technical Information of China (English)

    ZhangShuochengt; WangDan; QiaoWeimin; JingLan

    2003-01-01

    All kinds of step motors and servomotors are widely used in CSR control system, such as many vacuum valves control that set on the HIRFL-CSR; all kinds of electric switches and knobs of ECR Ion Source; equipment of CSR Beam Diagnostics and a lot of large equipment like Inside Gun Toroid and Collector Toroid of HIRFL. A typical control system include up to 32 16-I/O Control boards, and each 16-I/O Control board can control 4 motors at the same time (including 8 Limit Switches).

  1. Transformers and motors

    CERN Document Server

    Shultz, George

    1991-01-01

    Transformers and Motors is an in-depth technical reference which was originally written for the National Joint Apprenticeship Training Committee to train apprentice and journeymen electricians. This book provides detailed information for equipment installation and covers equipment maintenance and repair. The book also includes troubleshooting and replacement guidelines, and it contains a minimum of theory and math.In this easy-to-understand, practical sourcebook, you'll discover:* Explanations of the fundamental concepts of transformers and motors* Transformer connections and d

  2. Carnitine palmitoyltransferase 1C deficiency causes motor impairment and hypoactivity.

    Science.gov (United States)

    Carrasco, Patricia; Jacas, Jordi; Sahún, Ignasi; Muley, Helena; Ramírez, Sara; Puisac, Beatriz; Mezquita, Pau; Pié, Juan; Dierssen, Mara; Casals, Núria

    2013-11-01

    Carnitine palmitoyltransferase 1c (CPT1C), a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions, but its only known functions to date are involved in the hypothalamic control of energy homeostasis and in hippocampus-dependent spatial learning. To identify other physiological and behavioral functions of this protein, we performed a battery of neurological tests on Cpt1c-deficient mice. The animals showed intact autonomic and sensory systems, but some motor disturbances were observed. A more detailed study of motor function revealed impaired coordination and gait, severe muscle weakness, and reduced daily locomotor activity. Analysis of motor function in these mice at ages of 6-24 weeks showed that motor disorders were already present in young animals and that impairment increased progressively with age. Analysis of CPT1C expression in different motor brain areas during development revealed that CPT1C levels were low from birth to postnatal day 10 and then rapidly increased peaking at postnatal day 21, which suggests that CPT1C plays a relevant role in motor function during and after weaning. As CPT1C is known to regulate ceramide levels, we measured these biolipids in different motor areas in adult mice. Cerebellar, striatum, and motor cortex extracts from Cpt1c knockout mice showed reduced levels of ceramide and its derivative sphingosine when compared to wild-type animals. Our results indicate that altered ceramide metabolism in motor brain areas induced by Cpt1c deficiency causes progressive motor dysfunction from a young age. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Tuning Multiple Motor Travel Via Single Motor Velocity

    Science.gov (United States)

    Xu, Jing; Shu, Zhanyong; King, Stephen J.; Gross, Steven P.

    2012-01-01

    Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport. PMID:22672518

  4. 46 CFR 169.684 - Overcurrent protection for motors and motor branch circuits.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Overcurrent protection for motors and motor branch... motors and motor branch circuits. (a) Except as provided in paragraph (d) of this section, each motor... motor that is responsive to motor current or to both motor current and temperature may be used. (b)...

  5. Method for assessing motor insulation on operating motors

    Science.gov (United States)

    Kueck, John D.; Otaduy, Pedro J.

    1997-01-01

    A method for monitoring the condition of electrical-motor-driven devices. The method is achieved by monitoring electrical variables associated with the functioning of an operating motor, applying these electrical variables to a three phase equivalent circuit and determining non-symmetrical faults in the operating motor based upon symmetrical components analysis techniques.

  6. Fluorescence imaging of single Kinesin motors on immobilized microtubules.

    Science.gov (United States)

    Korten, Till; Nitzsche, Bert; Gell, Chris; Ruhnow, Felix; Leduc, Cécile; Diez, Stefan

    2011-01-01

    Recent developments in optical microscopy and nanometer tracking have greatly improved our understanding of cytoskeletal motor proteins. Using fluorescence microscopy, dynamic interactions are now routinely observed in vitro on the level of single molecules mainly using a geometry, where fluorescently labeled motors move on surface-immobilized filaments. In this chapter, we review recent methods related to single-molecule kinesin motility assays. In particular, we aim to provide practical advice on: how to set up the assays, how to acquire high-precision data from fluorescently labeled kinesin motors and attached quantum dots, and how to analyze data by nanometer tracking.

  7. General Motors sidestream separator

    Energy Technology Data Exchange (ETDEWEB)

    Tessier, R.J.

    1981-01-01

    On February 15, 1980, the United States Environmental Protection Agency, acting pursuant to Paragraph 113(D) (4) of the Clean Air Act, issued to General Motors an innovative technology order covering fifteen coal-fired spreader-stoker boilers located at six General Motors plants in Ohio. The purpose and effect of this order was to permit General Motors time to develop a new, innovative technique for controlling particulate emissions from the specified boilers before compliance with the federally approved Ohio particulate control regulation was required. This new technology was christened, The Sidestream Separator, by General Motors. It provides a highly cost effective means of reducing particulate emissions below levels currently obtainable with conventionally used high efficiency mechanical collectors. These improvements could prove to be of substantial benefit to many industrial facilities with spreader-stoker coal-fired boilers that cannot be brought into compliance with applicble air pollution regulations except by application of far more expensive and unwieldly electrostatic precipitators (ESP's) or fabric filters (baghouses).

  8. Motor Vehicle Safety

    Science.gov (United States)

    ... to prevent these crashes is one part of motor vehicle safety. Here are some things you can do to be safer on the road: Make sure your vehicle is safe and in working order Use car seats for children Wear your seat belt Don' ...

  9. Aprendizaje y desarrollo motor

    OpenAIRE

    Guillén Guillén, Eva I.

    2006-01-01

    El desarrollo evolutivo general del niño/a en relación con los procesos de maduración motora, procesos de aprendizaje y desarrollo motor. Técnicas de aprendizaje. Técnica de solución de conflictos. Balances musculares.

  10. Gas-operated motor systems

    Energy Technology Data Exchange (ETDEWEB)

    Rilett, J.W.

    1980-09-30

    A gas-operated motor system of the stored energy type-as disclosed in U.S. Pat. No. 4,092,830-in which the gas exhausted from the motor is ducted to a chamber during operation of the motor and thereafter compressed back into the gas reservoir vessel. Recompression may be achieved, e.g., by providing the exhaust gas chamber with a movable piston, or by running the motor in the reverse mode as a compressor.

  11. MOTORIC STIMULATION RELATED TO FINE MOTORIC DEVELOPMENT ON CHILD

    Directory of Open Access Journals (Sweden)

    Mira Triharini

    2017-07-01

    Full Text Available Introduction: Motor developmental stimulation is an activity undertaken to stimulate the children basic skills and so they can grow and develop optimally. Children who obtain a direct stimulus will grow faster than who get less stimulus. Mother’s behavior of stimulation is very important for children, it is considering as the basic needs of children and it must be fulfilled. Providing good stimulation could optimize fine motor development in children. The purpose of this study was to analyze mother’s behavior about motor stimulation with fine motor development in toddler age 4-5 years old. Method: Design have been  used in this study was cross sectional. Population were mothers and their toddler in Group A of Dharma Wanita Persatuan Driyorejo Gresik Preschool. Sample were 51 respondents recruited by using purposive sampling technique according to inclusion and exclusion criteria. The independent variable was mother’s behavior about motor stimulation whereas dependent variable was fine motor development in toddler. The data were collected using questionnaire and conducting observation on fine motor development based on Denver Development Screening Test (DDST. Data then analyzed using Spearman Rho (r test to find relation between mother’s behaviors about stimulation motor on their toddler fine motor development. Result: Results  of this study showed that there were correlations between mother’s knowledge and fine motor development in toddler (p=0.000, between mother’s attitude and fine motor development in toddler (p=0.000, and between mother’s actions and fine motor development in toddler (p=0.000. Analysis: In sort study found that there were relation between fine motor development and mother’s behavior. Discussion: Therefore mother’s behavior needed to be improved. Further research about stimulation motor and fine motor development aspects in toddler is required.

  12. Rotation of artificial rotor axles in rotary molecular motors.

    Science.gov (United States)

    Baba, Mihori; Iwamoto, Kousuke; Iino, Ryota; Ueno, Hiroshi; Hara, Mayu; Nakanishi, Atsuko; Kishikawa, Jun-Ichi; Noji, Hiroyuki; Yokoyama, Ken

    2016-10-04

    F1- and V1-ATPase are rotary molecular motors that convert chemical energy released upon ATP hydrolysis into torque to rotate a central rotor axle against the surrounding catalytic stator cylinder with high efficiency. How conformational change occurring in the stator is coupled to the rotary motion of the axle is the key unknown in the mechanism of rotary motors. Here, we generated chimeric motor proteins by inserting an exogenous rod protein, FliJ, into the stator ring of F1 or of V1 and tested the rotation properties of these chimeric motors. Both motors showed unidirectional and continuous rotation, despite no obvious homology in amino acid sequence between FliJ and the intrinsic rotor subunit of F1 or V1 These results showed that any residue-specific interactions between the stator and rotor are not a prerequisite for unidirectional rotation of both F1 and V1 The torque of chimeric motors estimated from viscous friction of the rotation probe against medium revealed that whereas the F1-FliJ chimera generates only 10% of WT F1, the V1-FliJ chimera generates torque comparable to that of V1 with the native axle protein that is structurally more similar to FliJ than the native rotor of F1 This suggests that the gross structural mismatch hinders smooth rotation of FliJ accompanied with the stator ring of F1.

  13. Light-driven molecular motors

    OpenAIRE

    van Delden, RA; FERINGA, BL; Kuzmany, H.; Fink, J.; Mehring, M.; Roth, S.

    2004-01-01

    Molecular motors can be defined as molecules that are able to convert any type of energy input (a fuel) into controlled motion. These systems can be categorized into linear and rotary motors, depending on the motion induced. This brief account will discuss the state of affairs of the research on light-driven rotary molecular motors.

  14. Piezoelectric Torsional Vibration Driven Motor

    Science.gov (United States)

    2000-10-29

    20 which can provide large amplitude rotational motion with a high torque. 21 Piezoelectric ultrasonic motors have been developed using traveling...Motor for High Torque", T. S. Glenn, W.G. Hagwood, SPIE Volume 3041, 4 1997. These piezoelectric ultrasonic motors are of limited application

  15. Experiments with a DC Motor

    Science.gov (United States)

    Kraftmakher, Yaakov

    2010-01-01

    Experiments with an electric motor provide good opportunity to demonstrate some basic laws of electricity and magnetism. The aim of the experiments with a low-power dc motor is to show how the motor approaches its steady rotation and how its torque, mechanical power and efficiency depend on the rotation velocity. The tight relationship between the…

  16. Coordinated switching of bacterial flagellar motors: evidence for direct motor-motor coupling?

    Science.gov (United States)

    Hu, Bo; Tu, Yuhai

    2013-01-01

    The swimming of Escherichia coli is powered by its multiple flagellar motors. Each motor spins either clockwise (CW) or counterclockwise (CCW), under the control of an intracellular regulator, CheY-P. There can be two mechanisms (extrinsic and intrinsic) to coordinate the switching of bacterial motors. The extrinsic one arises from the fact that different motors in the same cell sense a common input (CheY-P) which fluctuates near the motors' response threshold. An alternative, intrinsic mechanism is direct motor-motor coupling which makes synchronized switching energetically favorable. Here, we develop simple models for both mechanisms and uncover their different hallmarks. A quantitative comparison to the recent experiments suggest that the direct coupling mechanism may be accountable for the observed sharp correlation between motors in a single E. coli. Possible origins of this coupling (e.g., hydrodynamic interaction) are discussed. PMID:25167320

  17. Split-phase motor running as capacitor starts motor and as capacitor run motor

    OpenAIRE

    2016-01-01

    In this paper, the input parameters of a single phase split-phase induction motor is taken to investigate and to study the output performance characteristics of capacitor start and capacitor run induction motor. The value of these input parameters are used in the design characteristics of capacitor run and capacitor start motor with each motor connected to rated or standard capacitor in series with auxiliary winding or starting winding respectively for the normal operational condition. The ma...

  18. Collective transport of weakly interacting molecular motors with Langmuir kinetics

    Science.gov (United States)

    Chandel, Sameep; Chaudhuri, Abhishek; Muhuri, Sudipto

    2015-04-01

    Filament-based intracellular transport involves the collective action of molecular motor proteins. Experimental evidences suggest that microtubule (MT) filament bound motor proteins such as kinesins weakly interact among themselves during transport and with the surrounding cellular environment. Motivated by these observations we study a driven lattice gas model for collective unidirectional transport of molecular motors on open filament. This model incorporates short-range next-nearest-neighbour (NNN) interactions between the motors and couples the transport process on filament with surrounding cellular environment through adsorption-desorption Langmuir kinetics (LK) of the motors. We analyse this model within the framework of a mean-field (MF) theory in the limit of weak interactions between the motors. We point to the mapping of this model with the non-conserved version of the Katz-Lebowitz-Spohn (KLS) model. The system exhibits rich phase behavior with a variety of inhomogeneous phases including localized shocks in the bulk of the filament. We obtain the steady-state density and current profiles, analyse their variation as a function of the strength of interaction and construct the non-equilibrium MF phase diagram. We compare these MF results with Monte Carlo simulations and find that the MF analysis shows reasonably good agreement with simulation results as long as the motors are weakly interacting. For sufficently strong NNN interaction between the motors, the mean-field results deviate significantly, and for very strong NNN interaction in the absence of LK, the current in the lattice is determined solely by the NNN interaction parameter and it becomes independent of entry and exit rates of motors at the filament boundaries.

  19. Control linear motor with DSP

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Han

    2003-06-15

    This book consists of control linear motor with DSP, which is composed of two parts. The title of the first part is control Algorithm and software with introduction and tracking controller, drive profile on decision of motion time, floating point DSP and quantization effect, motion override Algorithm and drive profile summary, design of digital controller on design for controller structure and analysis of PID control Loop and Motor turning, design for IIR digital filter and protocol structure for communication wit host. The second part describes control hardware, which mentions Linear motor and Amplifier, motor and power supply, DSP board and interface, control of Micro Linear Stepping Motor and conclusion.

  20. Acute exercise improves motor memory

    DEFF Research Database (Denmark)

    Skriver, Kasper Christen; Roig, Marc; Lundbye-Jensen, Jesper

    2014-01-01

    We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory...... practice whereas lactate correlated with better retention 1 hour as well as 24 hours and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning...... processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory....

  1. Magnetostrictive direct drive motors

    Science.gov (United States)

    Naik, Dipak; Dehoff, P. H.

    1992-01-01

    A new rare earth alloy, Terfenol-D, combines low frequency operation and extremely high energy density with high magnetostriction. Its material properties make it suitable as a drive element for actuators requiring high output torque. The high strains, the high forces and the high controllability of Terfenol alloys provide a powerful and challenging basis for new ways to generate motion in actuators. Two prototypes of motors using Terfenol-D rods were developed at NASA Goddard. The basic principles of operation are provided of the motor along with other relevant details. A conceptual design of a torque limiting safety clutch/brake under development is illustrated. Also, preliminary design drawings of a linear actuator using Terfenol-D is shown.

  2. Understanding social motor coordination.

    Science.gov (United States)

    Schmidt, R C; Fitzpatrick, Paula; Caron, Robert; Mergeche, Joanna

    2011-10-01

    Recently there has been much interest in social coordination of motor movements, or as it is referred to by some researchers, joint action. This paper reviews the cognitive perspective's common coding/mirror neuron theory of joint action, describes some of its limitations and then presents the behavioral dynamics perspective as an alternative way of understanding social motor coordination. In particular, behavioral dynamics' ability to explain the temporal coordination of interacting individuals is detailed. Two experiments are then described that demonstrate how dynamical processes of synchronization are apparent in the coordination underlying everyday joint actions such as martial art exercises, hand-clapping games, and conversations. The import of this evidence is that emergent dynamic patterns such as synchronization are the behavioral order that any neural substrate supporting joint action (e.g., mirror systems) would have to sustain.

  3. Ironless armature torque motor

    Science.gov (United States)

    Fisher, R. L.

    1972-01-01

    Four iron-less armature torque motors, four Hall device position sensor assemblies, and two test fixtures were fabricated. The design approach utilized samarium cobalt permanent magnets, a large airgap, and a three-phase winding in a stationary ironless armature. Hall devices were employed to sense rotor position. An ironless armature torque motor having an outer diameter of 4.25 inches was developed to produce a torque constant of 65 ounce-inches per ampere with a resistance of 20.5 ohms. The total weight, including structural elements, was 1.58 pounds. Test results indicated that all specifications were met except for generated voltage waveform. It is recommended that investigations be made concerning the generated voltage waveform to determine if it may be improved.

  4. Efficient differentiation of mouse embryonic stem cells into motor neurons.

    Science.gov (United States)

    Wu, Chia-Yen; Whye, Dosh; Mason, Robert W; Wang, Wenlan

    2012-06-09

    Direct differentiation of embryonic stem (ES) cells into functional motor neurons represents a promising resource to study disease mechanisms, to screen new drug compounds, and to develop new therapies for motor neuron diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Many current protocols use a combination of retinoic acid (RA) and sonic hedgehog (Shh) to differentiate mouse embryonic stem (mES) cells into motor neurons. However, the differentiation efficiency of mES cells into motor neurons has only met with moderate success. We have developed a two-step differentiation protocol that significantly improves the differentiation efficiency compared with currently established protocols. The first step is to enhance the neuralization process by adding Noggin and fibroblast growth factors (FGFs). Noggin is a bone morphogenetic protein (BMP) antagonist and is implicated in neural induction according to the default model of neurogenesis and results in the formation of anterior neural patterning. FGF signaling acts synergistically with Noggin in inducing neural tissue formation by promoting a posterior neural identity. In this step, mES cells were primed with Noggin, bFGF, and FGF-8 for two days to promote differentiation towards neural lineages. The second step is to induce motor neuron specification. Noggin/FGFs exposed mES cells were incubated with RA and a Shh agonist, Smoothened agonist (SAG), for another 5 days to facilitate motor neuron generation. To monitor the differentiation of mESs into motor neurons, we used an ES cell line derived from a transgenic mouse expressing eGFP under the control of the motor neuron specific promoter Hb9. Using this robust protocol, we achieved 51 ± 0.8% of differentiation efficiency (n = 3; p motor neuron specific markers, Islet-1 and choline acetyltransferase (ChAT). Our two-step differentiation protocol provides an efficient way to differentiate mES cells into spinal motor neurons.

  5. Steps in the bacterial flagellar motor.

    Directory of Open Access Journals (Sweden)

    Thierry Mora

    2009-10-01

    Full Text Available The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps. Here we propose a simple physical model, based on the storage of energy in protein springs, that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. We also predict a sublinear speed versus torque relationship for fixed load at low torque, and a peak in rotor diffusion as a function of torque. Our model provides a comprehensive framework for understanding and analyzing stepping behavior in the bacterial flagellar motor and proposes novel, testable predictions. More broadly, the storage of energy in protein springs by the flagellar motor may provide useful general insights into the design of highly efficient molecular machines.

  6. 350 KVA motor generators

    CERN Multimedia

    CERN PhotoLab

    1974-01-01

    Each logic circuit in the central computers consumes only a fraction of a watt: however, the final load constituted by many such circuits plus peripheral equipment is nearly half a million watts. Shown here are two 350 KVA motor generators used to convert 50 Hz mains to 60 Hz (US standard). Flywheels on the M.G. shafts remove power dropouts of up to 0.5 s.

  7. The St. Louis Motor

    Science.gov (United States)

    Greenslade, Thomas B.

    2011-10-01

    The St. Louis Motor, invented in 1909, is unique among physics apparatus for being named for a geographical place rather than a physicist. The sturdy little device (Fig. 1) has never been out of production. Any older school or physics department that has not done a catastrophic housecleaning in the last 20 years will certainly have a small flock of them in the back room.

  8. Motor neurone disease.

    Science.gov (United States)

    2016-03-23

    Essential facts Motor neurone disease describes a group of related diseases, affecting the neurones in the brain and spinal cord. Progressive, incurable and life-limiting, MND is rare, with about 1,100 people developing it each year in the UK and up to 5,000 people affected at any one time. One third of people will die within a year of diagnosis and more than half within two years. About 5% to 10% are alive at ten years.

  9. An Electrostatic Stepper Motor

    Science.gov (United States)

    Partington, E. C.; Wong, Edward Chun Kay; Bullough, W. A.

    This paper describes a new concept in pulse controlled motor and precision linear actuator techniques. Piezo translators [PZT] employed to provide reciprocating primary motion are connected to a load via a controllable electrorheological fluid [ERF] clutch to form a programmable speed and step-width drive. Ideal considerations are used to quantify the limiting potential of the drive and details are given of its development and progress.

  10. Lumbosacral motor polyneuropathy

    Directory of Open Access Journals (Sweden)

    S. A. Malmberg

    2012-01-01

    Full Text Available The case of lumbosacral motor neuropathy (LSMN in 15-yers old patient with diabetes mellitus (type I is presented. Clinical and electromyographical patterns are considered and effectiveness of corticosteroid therapy is estimated. The differential features and taxonomic position of LSMN and chronic inflammatory demyelinating polyneuropathy (CIDP are discussed. The necessity of some liberalization of CIDP diagnostic criteria is demonstrated.

  11. Motor Fuel Excise Taxes

    Energy Technology Data Exchange (ETDEWEB)

    2015-09-01

    A new report from the National Renewable Energy Laboratory (NREL) explores the role of alternative fuels and energy efficient vehicles in motor fuel taxes. Throughout the United States, it is common practice for federal, state, and local governments to tax motor fuels on a per gallon basis to fund construction and maintenance of our transportation infrastructure. In recent years, however, expenses have outpaced revenues creating substantial funding shortfalls that have required supplemental funding sources. While rising infrastructure costs and the decreasing purchasing power of the gas tax are significant factors contributing to the shortfall, the increased use of alternative fuels and more stringent fuel economy standards are also exacerbating revenue shortfalls. The current dynamic places vehicle efficiency and petroleum use reduction polices at direct odds with policies promoting robust transportation infrastructure. Understanding the energy, transportation, and environmental tradeoffs of motor fuel tax policies can be complicated, but recent experiences at the state level are helping policymakers align their energy and environmental priorities with highway funding requirements.

  12. Dyspraxia, motor function and visual-motor integration in autism.

    Science.gov (United States)

    Miller, M; Chukoskie, L; Zinni, M; Townsend, J; Trauner, D

    2014-08-01

    This project assessed dyspraxia in high-functioning school aged children with autism with a focus on Ideational Praxis. We examined the association of specific underlying motor function including eye movement with ideational dyspraxia (sequences of skilled movements) as well as the possible role of visual-motor integration in dyspraxia. We found that compared to IQ-, sex- and age-matched typically developing children, the children with autism performed significantly worse on: Ideational and Buccofacial praxis; a broad range of motor tests, including measures of simple motor skill, timing and accuracy of saccadic eye movements and motor coordination; and tests of visual-motor integration. Impairments in individual children with autism were heterogeneous in nature, although when we examined the praxis data as a function of a qualitative measure representing motor timing, we found that children with poor motor timing performed worse on all praxis categories and had slower and less accurate eye movements while those with regular timing performed as well as typical children on those same tasks. Our data provide evidence that both motor function and visual-motor integration contribute to dyspraxia. We suggest that dyspraxia in autism involves cerebellar mechanisms of movement control and the integration of these mechanisms with cortical networks implicated in praxis.

  13. How molecular motors are arranged on a cargo is important for vesicular transport.

    Science.gov (United States)

    Erickson, Robert P; Jia, Zhiyuan; Gross, Steven P; Yu, Clare C

    2011-05-01

    The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

  14. How molecular motors are arranged on a cargo is important for vesicular transport.

    Directory of Open Access Journals (Sweden)

    Robert P Erickson

    2011-05-01

    Full Text Available The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s, significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

  15. 77 FR 11598 - Thermal Overload Protection for Electric Motors on Motor-Operated Valves

    Science.gov (United States)

    2012-02-27

    ... COMMISSION Thermal Overload Protection for Electric Motors on Motor-Operated Valves AGENCY: Nuclear... for Electric Motors on Motor-Operated Valves.'' This regulatory guide describes a method acceptable to... devices that are integral with the motor starter for electric motors on motor-operated valves....

  16. A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus.

    Directory of Open Access Journals (Sweden)

    Mattia Gazzola

    2009-12-01

    Full Text Available Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors.

  17. A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus.

    Science.gov (United States)

    Gazzola, Mattia; Burckhardt, Christoph J; Bayati, Basil; Engelke, Martin; Greber, Urs F; Koumoutsakos, Petros

    2009-12-01

    Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors.

  18. Microtubule length dependence of motor traffic in cells

    CERN Document Server

    Zhang, Yunxin

    2012-01-01

    In living cells, motor proteins, such as kinesin and dynein can move processively along microtubule (MT), and also detach from or attach to MT stochastically. Experiments have found that, the traffic of motor might be jammed, and various theoretical models have been designed to understand this traffic jam phenomenon. But previous studies mainly focus on motor attachment/detachment rate dependent properties. Recent experiment of Leduc {\\it et al.} found that the traffic jam formation of motor protein kinesin depends also on the length of MT [Proc. Natl. Acad. Sci. U.S.A. {\\bf 109}, 6100-6105 (2012)]. In this study, the MT length dependent properties of motor traffic will be analyzed. We found that MT length has one {\\it critical value} $N_c$, traffic jam occurs only when MT length $N>N_c$. The jammed length of MT increases with total MT length, while the non-jammed MT length might not change monotonically with the total MT length. The critical value $N_c$ increases with motor detachment rate from MT, but decre...

  19. A synthetic DNA motor that transports nanoparticles along carbon nanotubes

    Science.gov (United States)

    Cha, Tae-Gon; Pan, Jing; Chen, Haorong; Salgado, Janette; Li, Xiang; Mao, Chengde; Choi, Jong Hyun

    2014-01-01

    Intracellular protein motors have evolved to perform specific tasks critical to the function of cells such as intracellular trafficking and cell division. Kinesin and dynein motors, for example, transport cargoes in living cells by walking along microtubules powered by adenosine triphosphate hydrolysis. These motors can make discrete 8 nm centre-of-mass steps and can travel over 1 µm by changing their conformations during the course of adenosine triphosphate binding, hydrolysis and product release. Inspired by such biological machines, synthetic analogues have been developed including self-assembled DNA walkers that can make stepwise movements on RNA/DNA substrates or can function as programmable assembly lines. Here, we show that motors based on RNA-cleaving DNA enzymes can transport nanoparticle cargoes--CdS nanocrystals in this case--along single-walled carbon nanotubes. Our motors extract chemical energy from RNA molecules decorated on the nanotubes and use that energy to fuel autonomous, processive walking through a series of conformational changes along the one-dimensional track. The walking is controllable and adapts to changes in the local environment, which allows us to remotely direct `go' and `stop' actions. The translocation of individual motors can be visualized in real time using the visible fluorescence of the cargo nanoparticle and the near-infared emission of the carbon-nanotube track. We observed unidirectional movements of the molecular motors over 3 µm with a translocation velocity on the order of 1 nm min-1 under our experimental conditions.

  20. Neurological impairment in nephropathic cystinosis: motor coordination deficits.

    Science.gov (United States)

    Trauner, Doris A; Williams, Jennifer; Ballantyne, Angela O; Spilkin, Amy M; Crowhurst, Jennifer; Hesselink, John

    2010-10-01

    Nephropathic cystinosis is a rare genetic metabolic disorder that results in accumulation of the amino acid cystine in lysosomes due to lack of a cystine-specific transporter protein. Cystine accumulates in cells throughout the body and causes progressive damage to multiple organs, including the brain. Neuromotor deficits have been qualitatively described in individuals with cystinosis. This study quantitatively examined fine-motor coordination in individuals with cystinosis. Brain magnetic resonance imaging (MRI) scans were also performed to determine whether structural changes were associated with motor deficits. Participants were 52 children and adolescents with infantile nephropathic cystinosis and 49 controls, ages 2-17 years, divided into preacademic and school-age groups. Results indicated that both the preacademic and school-age cystinosis groups performed significantly more poorly than their matched control groups on the Motor Coordination Test. Further, the level of performance was not significantly different between the preacademic and school-age groups. There were no significant differences in motor coordination scores based on MRI findings. This is the first study to document a persistent, nonprogressive, fine-motor coordination deficit in children and adolescents with cystinosis. The fact that these difficulties are present in the preschool years lends further support to the theory that cystinosis adversely affects neurological functioning early in development. The absence of a relationship between brain structural changes and motor function suggests that an alternative cause for motor dysfunction must be at work in this disorder.

  1. Segmented motor drive - with multi-phase induction motor

    DEFF Research Database (Denmark)

    Bendixen, Flemming Buus

    This PhD project commences in modulation of motor drives, i.e. having the advantage of reducing the number of variants and improves the system reliability at error situations. Four different motor drive topologies with modular construction as common denominator are compared on a general level....... The multi-phase motor is selected for further analysis. The project is limited to examine if increasing the number of phases can improve the characteristics for induction motor drives. In the literature it is demonstrated that torque production in a six-phase motor can be increased, if a 3rd harmonic...... current with 1/6 amplitude is added to the 1st harmonic current. This claim is verified and the optimization of the motor design is extended to, beyond the stator tooth width, also to include the inner diameter of the stator. This means that the lamination sheet is optimized according to two geometrical...

  2. Acute autonomic, sensory and motor neuropathy associated with meningoencephalitis.

    Science.gov (United States)

    Kinoshita, Satoko; Sugie, Kazuma; Kataoka, Hiroshi; Sugie, Miho; Hirano, Makito; Ueno, Satoshi

    2009-01-01

    We report the first case of acute autonomic, motor and sensory neuropathy (AASMN) associated with meningoencephalitis. A 62-year-old man presented with fever, neck stiffness, and coma. Respiratory failure developed. Magnetic resonance images showed an abnormality in the medial temporal lobe. Cerebrospinal fluid analysis revealed pleocytosis with a high protein level. Intensive care gradually improved the consciousness level, but paralysis of the four extremities persisted. Nerve conduction studies revealed demyelinating sensory and motor polyneuropathy. Severe orthostatic hypotension, urinary retention, and constipation were also present. Clinical autonomic tests suggested both sympathetic and parasympathetic dysfunction. After intravenous immunoglobulin therapy, motor and sensory symptoms resolved rapidly; dysautonomia resolved gradually over the next 2 months. The response to immunological therapy and the presence of antecedent infection suggest that AASMN is a postinfectious, immune-mediated, autonomic, sensory and motor nervous system dysfunction.

  3. Functional motor microdomains of the outer hair cell lateral membrane.

    Science.gov (United States)

    Santos-Sacchi, Joseph

    2002-12-01

    The outer hair cell (OHC) of the mammalian inner ear is a highly partitioned neuroepithelial cell whose lateral membrane is devoted to electromotility, a fast mechanical length change owing to the motor protein, prestin. Spatially restricted measures of prestin-derived nonlinear capacitance or gating charge, using either electrical amputation or discrete membrane mechanical deformation, were used to determine that functional variation exists within the extensive lateral membrane of the cell. This was evidenced by variation in the motor's operating voltage range and sensitivity among microdomains within the lateral membrane. That is, localized regions of the membrane evidenced Boltzmann distributions of motor charge whose midpoint voltage and slope differed from those obtained for the whole cell. These data highlight the functional independence of microdomains and imply that measured whole cell characteristics may differ from the microscopic characteristics of elementary motors.

  4. 75 FR 76692 - Federal Motor Vehicle Safety Standards; Small Business Impacts of Motor Vehicle Safety

    Science.gov (United States)

    2010-12-09

    ..., and 571 Federal Motor Vehicle Safety Standards; Small Business Impacts of Motor Vehicle Safety AGENCY... passenger vehicles, trucks, buses, trailers, incomplete vehicles, motorcycles, and motor vehicle...

  5. Adequate sizing and motor exploitation: Motor energy management

    Directory of Open Access Journals (Sweden)

    Kostić Miloje M.

    2011-01-01

    Full Text Available Motor energy management includes adequate sizing, control and improvement of electric energy quality, i.e. voltage quality (reducing voltage unbalance and harmonics distortion, and the proper maintenance. The specific motor price per kW is approximately constant for motors rated from 5 kW to 20 kW. By adequate sizing, or by proper replacement of the old motor with the new one, with rated output power reduced by 20% to 50% the smaller motor will be also cheaper by 20% to 50%. When the 22 kW motor is replaced with the new 15 kW that costs 64% of the price of a new 22 kW motor, the efficiency is increased by 3.6% (Example in paper. On the basis of our investigation results, it is confirmed that there are significant possibilities for energy savings by setting voltage values within the ±5% voltage band (Un±5%, since more than 80% induction motors are under loaded (£70%, especially small and medium rated power (1-30 kW motors.

  6. dnc-1/dynactin 1 knockdown disrupts transport of autophagosomes and induces motor neuron degeneration.

    Science.gov (United States)

    Ikenaka, Kensuke; Kawai, Kaori; Katsuno, Masahisa; Huang, Zhe; Jiang, Yue-Mei; Iguchi, Yohei; Kobayashi, Kyogo; Kimata, Tsubasa; Waza, Masahiro; Tanaka, Fumiaki; Mori, Ikue; Sobue, Gen

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. We previously showed that the expression of dynactin 1, an axon motor protein regulating retrograde transport, is markedly reduced in spinal motor neurons of sporadic ALS patients, although the mechanisms by which decreased dynactin 1 levels cause neurodegeneration have yet to be elucidated. The accumulation of autophagosomes in degenerated motor neurons is another key pathological feature of sporadic ALS. Since autophagosomes are cargo of dynein/dynactin complexes and play a crucial role in the turnover of several organelles and proteins, we hypothesized that the quantitative loss of dynactin 1 disrupts the transport of autophagosomes and induces the degeneration of motor neuron. In the present study, we generated a Caenorhabditis elegans model in which the expression of DNC-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model. Thus, our results suggest that decreased expression of dynactin 1 induces motor neuron degeneration and that the transport of autophagosomes is a novel and substantial therapeutic target for motor neuron degeneration.

  7. dnc-1/dynactin 1 knockdown disrupts transport of autophagosomes and induces motor neuron degeneration.

    Directory of Open Access Journals (Sweden)

    Kensuke Ikenaka

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. We previously showed that the expression of dynactin 1, an axon motor protein regulating retrograde transport, is markedly reduced in spinal motor neurons of sporadic ALS patients, although the mechanisms by which decreased dynactin 1 levels cause neurodegeneration have yet to be elucidated. The accumulation of autophagosomes in degenerated motor neurons is another key pathological feature of sporadic ALS. Since autophagosomes are cargo of dynein/dynactin complexes and play a crucial role in the turnover of several organelles and proteins, we hypothesized that the quantitative loss of dynactin 1 disrupts the transport of autophagosomes and induces the degeneration of motor neuron. In the present study, we generated a Caenorhabditis elegans model in which the expression of DNC-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model. Thus, our results suggest that decreased expression of dynactin 1 induces motor neuron degeneration and that the transport of autophagosomes is a novel and substantial therapeutic target for motor neuron degeneration.

  8. Sport expert's motor imagery: functional imaging of professional motor skills and simple motor skills.

    Science.gov (United States)

    Wei, Gaoxia; Luo, Jing

    2010-06-23

    Numerous studies provide evidence that motor skill acquisition is associated with dynamic changes in cortical and subcortical regions. Athletes are a professional population who are engaged in extensive motor training for long periods. However, the neural substrates of extreme level motor performance have not been clarified. We used kinesthetic imagery task to induce the mental representation of sport expert's extraordinary performance in view of the shared substrates of executing movement and motor imagery. For the first time, we compared, through functional magnetic resonance imaging (fMRI), the pattern of cerebral activations in 12 professional divers and 12 normal people without extensive training, during imagery of professional skills and imagery of simple motor skills. The sport experts showed significant activation in the parahippocampus during imagery of professional skills relative to the novices, which might reflect the representation adapted to experience-related motor tasks. No significant difference was found between experts and novices when they imagined simple motor skills. These results indicated the experts might utilize their kinesthetic imagery more efficiently than novices, but only for the activity in which they had expertise. The sport experts also demonstrated more focused activation patterns in prefrontal areas in both of imagery tasks, which may be relevant to higher order of motor control during motor imagery. Moreover, this study suggested that the brains of sport experts could be regarded as the ideal subjects to explore the relationship between cerebral plasticity and learning of complex motor skills.

  9. Savonius wind motor

    Energy Technology Data Exchange (ETDEWEB)

    Kalopoulos, G.D.

    1993-01-13

    The Savonius motor has a plurality of floor or vertical stages, each floor comprising a pair of semicylindrical blades contained between two parallel horizontal circular discs, the blades being diametrically disposed so that one blade surmounts the other by a lead of 1/8th of their diameter. The bladings in each floor are arranged at a phase difference, so that it becomes possible to exploit even weak winds independent of the direction they blow from and without the wind engine being equipped with a special orientation system. (author)

  10. Control of synchronous motors

    CERN Document Server

    Louis, Jean-Paul

    2013-01-01

    Synchronous motors are indubitably the most effective device to drive industrial production systems and robots with precision and rapidity. Their control law is thus critical for combining at the same time high productivity to reduced energy consummation. As far as possible, the control algorithms must exploit the properties of these actuators. Therefore, this work draws on well adapted models resulting from the Park's transformation, for both the most traditional machines with sinusoidal field distribution and for machines with non-sinusoidal field distribution which are more and more used in

  11. A bottom hole motor

    Energy Technology Data Exchange (ETDEWEB)

    Kibishcher, G.B.; Karpenko, V.K.; Pogorelov, V.P.

    1982-01-01

    A bottom hole motor is proposed which includes a body, a push rod with a piston, a spindle, a mechanism for converting the reciprocal movement of the piston into rotation of the shaft and pump and drain cavities. In order to simplify the design the push rod is made with radial openings above and below the piston, while the shaft is made with two longitudinal channels at the level of the radial openings of the push rod on the diametrically opposite sides. The cavity of one channel is constantly connected with the pump cavity, while the other is permanently connected with the drain cavity.

  12. Motor timing under microgravity.

    Science.gov (United States)

    Semjen, A; Leone, G; Lipshits, M

    1998-01-01

    Five participants were tested on their ability to produce accurate and regular inter-response intervals in the 350 to 530 ms time range. Three of them were members of the French-Russian CASSIOPEE 96 spaceflight mission, and the other two were control subjects tested on the ground. During spaceflight, the target inter-response intervals were increasingly undershot and the timing became more variable (less regular). The increase in the timing variability was mostly attributable to the internal timekeeping processes rather than those involved in motor execution. The results are discussed with reference to the physiological mechanisms possibly underlying the timing of fast serial movements.

  13. Motor cortical plasticity induced by motor learning through mental practice.

    Directory of Open Access Journals (Sweden)

    Laura eAvanzino

    2015-04-01

    Full Text Available Several investigations suggest that actual and mental actions trigger similar neural substrates. Motor learning via physical practice results in long-term potentiation (LTP-like plasticity processes, namely potentiation of M1 and a temporary occlusion of additional LTP-like plasticity. However, whether this neuroplasticity process contributes to improve motor performance through mental practice remains to be determined. Here, we tested skill learning-dependent changes in primary motor cortex (M1 excitability and plasticity by means of transcranial magnetic stimulation in subjects trained to physically execute or mentally perform a sequence of finger opposition movements. Before and after physical practice and motor-imagery practice, M1 excitability was evaluated by measuring the input-output (IO curve of motor evoked potentials. M1 long-term potentiation (LTP and long-term depression (LTD-like plasticity was assessed with paired-associative stimulation (PAS of the median nerve and motor cortex using an interstimulus interval of 25 ms (PAS25 or 10 ms (PAS10, respectively. We found that even if after both practice sessions subjects significantly improved their movement speed, M1 excitability and plasticity were differentially influenced by the two practice sessions. First, we observed an increase in the slope of IO curve after physical but not after motor-imagery practice. Second, there was a reversal of the PAS25 effect from LTP-like plasticity to LTD-like plasticity following physical and motor-imagery practice. Third, LTD-like plasticity (PAS10 protocol increased after physical practice, whilst it was occluded after motor-imagery practice. In conclusion, we demonstrated that motor-imagery practice lead to the development of neuroplasticity, as it affected the PAS25- and PAS10- induced plasticity in M1. These results, expanding the current knowledge on how motor-imagery training shapes M1 plasticity, might have a potential impact in

  14. Movimento browniano e motores brownianos

    OpenAIRE

    Rezende, Guilherme Rocha de

    2012-01-01

    Neste trabalho utilizamos o formalismo da equação de Langevin generalizada, desenvolvido inicialmente por Robert Zwanzig e Hazime Mori, para estudarmos o comportamento de um tipo de motor browniano o motor liga-desliga aplicado no estudo de um separador de partículas e em um tipo de motor molecular: a cinesina. Neste estudo escolhemos quatro funções memórias diferentes e analisamos a influência destas memórias na velocidade e eficiência do motor browniano. ____________________________________...

  15. Overview of Bearingless Induction Motors

    Directory of Open Access Journals (Sweden)

    Xiaodong Sun

    2014-01-01

    Full Text Available Bearingless induction motors combining functions of both torque generation and noncontact magnetic suspension together have attracted more and more attention in the past decades due to their definite advantages of compactness, simple structure, less maintenance, no wear particles, high rotational speed, and so forth. This paper overviews the key technologies of the bearingless induction motors, with emphasis on motor topologies, mathematical models, and control strategies. Particularly, in the control issues, the vector control, independent control, direct torque control, nonlinear decoupling control, sensorless control, and so forth are investigated. In addition, several possible development trends of the bearingless induction motors are also discussed.

  16. The reciprocal coordination and mechanics of molecular motors in living cells.

    Science.gov (United States)

    Laib, Jeneva A; Marin, John A; Bloodgood, Robert A; Guilford, William H

    2009-03-03

    Molecular motors in living cells are involved in whole-cell locomotion, contractility, developmental shape changes, and organelle movement and positioning. Whether motors of different directionality are functionally coordinated in cells or operate in a semirandom "tug of war" is unclear. We show here that anterograde and retrograde microtubule-based motors in the flagella of Chlamydomonas are regulated such that only motors of a common directionality are engaged at any single time. A laser trap was used to position microspheres on the plasma membrane of immobilized paralyzed Chlamydomonas flagella. The anterograde and retrograde movements of the microsphere were measured with nanometer resolution as microtubule-based motors engaged the transmembrane protein FMG-1. An average of 10 motors acted to move the microsphere in either direction. Reversal of direction during a transport event was uncommon, and quiescent periods separated every transport event, suggesting the coordinated and exclusive action of only a single motor type. After a jump to 32 degrees C, temperature-sensitive mutants of kinesin-2 (fla10) showed exclusively retrograde transport events, driven by 7 motors on average. These data suggest that molecular motors in living cells can be reciprocally coordinated to engage simultaneously in large numbers and for exclusive transport in a single direction, even when a mixed population of motors is present. This offers a unique model for studying the mechanics, regulation, and directional coordination of molecular motors in a living intracellular environment.

  17. Interferometric Scattering Microscopy for the Study of Molecular Motors.

    Science.gov (United States)

    Andrecka, J; Takagi, Y; Mickolajczyk, K J; Lippert, L G; Sellers, J R; Hancock, W O; Goldman, Y E; Kukura, P

    2016-01-01

    Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis. Our approach is relevant not only for motor protein dynamics but also provides a general tool for single-particle tracking with high spatiotemporal precision, which overcomes the limitations of single-molecule fluorescence methods.

  18. Motor power control circuit for ac induction motors

    Science.gov (United States)

    Nola, F. J. (Inventor)

    1983-01-01

    A motor power control of the type which functions by controlling the power factor wherein one of the parameters of power factor current on time is determined by the on time of a triac through which current is supplied to the motor. By means of a positive feedback circuit, a wider range of control is effected.

  19. Segmented motor drive - with multi-phase induction motor

    DEFF Research Database (Denmark)

    Bendixen, Flemming Buus

    of the induction motor is set up. The model is able to calculate dynamical electric, magnetic and mechanic state variables, but initially it is used to calculate static characteristics in motors with different number of phases and different voltage supply shapes. This analysis show i.e. that the efficiency...... dimensions. The possible torque increase proves to be strongly dependent on the physical dimensions in the initial three-phase motor. The torque increase according to the optimization is listed for a range of Grundfos motors, but in most cases the increase is only a few percent. In a single example...... with 3rd harmonic or square. Another tendency is that the torque ripple is decreased as the number of phases is increased, regardless of the supply type used. Torque ripple can be a source of acoustic noise generation, in this context a multi-phase motor can therefore be an advantage. According...

  20. By Staying Together, Two Genes Keep the Motor Running.

    Science.gov (United States)

    Zhulin, Igor B

    2017-02-07

    In this issue of Structure, Lynch et al. (2017) reveal that the interaction between two key proteins in the bacterial flagellar motor results in a shared structural domain. This unusual arrangement keeps the corresponding genes together through the course of evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Energy-saving motor; Energiesparmotor

    Energy Technology Data Exchange (ETDEWEB)

    Lindegger, M.

    2002-07-01

    This report for the Swiss Federal Office of Energy (SFOE) describes the development and testing of an advanced electrical motor using a permanent-magnet rotor. The aims of the project - to study the technical feasibility and market potential of the Eco-Motor - are discussed and the three phases of the project described. These include the calculation and realisation of a 250-watt prototype operating at 230 V, the measurement of the motor's characteristics as well as those of a comparable asynchronous motor on the test bed at the University of Applied Science in Lucerne, Switzerland, and a market study to establish if the Eco-Motor and its controller can compete against normal asynchronous motors. Also, the results of an analysis of the energy-savings potential is made, should such Eco-Motors be used. Detailed results of the three phases of the project are presented and the prospects of producing such motors in Switzerland for home use as well as for export are examined.

  2. Power control for ac motor

    Science.gov (United States)

    Dabney, R. W. (Inventor)

    1984-01-01

    A motor controller employing a triac through which power is supplied to a motor is described. The open circuit voltage appearing across the triac controls the operation of a timing circuit. This timing circuit triggers on the triac at a time following turn off which varies inversely as a function of the amplitude of the open circuit voltage of the triac.

  3. Motor Coordination and Executive Functions

    Science.gov (United States)

    Michel, Eva

    2012-01-01

    Since Piaget, the view that motor and cognitive development are interrelated has gained wide acceptance. However, empirical research on this issue is still rare. Few studies show a correlation of performance in cognitive and motor tasks in typically developing children. More specifically, Diamond A. (2000) hypothesizes an involvement of executive…

  4. Motor Coordination and Executive Functions

    Science.gov (United States)

    Michel, Eva

    2012-01-01

    Since Piaget, the view that motor and cognitive development are interrelated has gained wide acceptance. However, empirical research on this issue is still rare. Few studies show a correlation of performance in cognitive and motor tasks in typically developing children. More specifically, Diamond A. (2000) hypothesizes an involvement of executive…

  5. Energy-saving motor; Energiesparmotor

    Energy Technology Data Exchange (ETDEWEB)

    Lindegger, M.

    2002-07-01

    This report for the Swiss Federal Office of Energy (SFOE) describes the development and testing of an advanced electrical motor using a permanent-magnet rotor. The aims of the project - to study the technical feasibility and market potential of the Eco-Motor - are discussed and the three phases of the project described. These include the calculation and realisation of a 250-watt prototype operating at 230 V, the measurement of the motor's characteristics as well as those of a comparable asynchronous motor on the test bed at the University of Applied Science in Lucerne, Switzerland, and a market study to establish if the Eco-Motor and its controller can compete against normal asynchronous motors. Also, the results of an analysis of the energy-savings potential is made, should such Eco-Motors be used. Detailed results of the three phases of the project are presented and the prospects of producing such motors in Switzerland for home use as well as for export are examined.

  6. 46 CFR 111.70-3 - Motor controllers and motor-control centers.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Motor controllers and motor-control centers. 111.70-3... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motor Circuits, Controllers, and Protection § 111.70-3 Motor controllers and motor-control centers. (a) General. The enclosure for each motor controller or...

  7. Enhanced Diffusion of Molecular Motors in the Presence of Adenosine Triphosphate and External Force

    Science.gov (United States)

    Shinagawa, Ryota; Sasaki, Kazuo

    2016-06-01

    The diffusion of a molecular motor in the presence of a constant external force is considered on the basis of a simple theoretical model. The motor is represented by a Brownian particle moving in a series of parabolic potentials placed periodically on a line, and the potential is switched stochastically from one parabola to another by a chemical reaction, which corresponds to the hydrolysis or synthesis of adenosine triphosphate (ATP) in motor proteins. It is found that the diffusion coefficient as a function of the force exhibits peaks. The mechanism of this diffusion enhancement and the possibility of observing it in F1-ATPase, a biological rotary motor, are discussed.

  8. From Conformational Spread to Allosteric and Cooperative models of E. coli flagellar motor

    CERN Document Server

    Pezzotta, Alberto; Celani, Antonio

    2016-01-01

    Escherichia coli swims using flagella activated by rotary motors. The direction of rotation of the motors is indirectly regulated by the binding of a single messenger protein. The conformational spread model has been shown to accurately describe the equilibrium properties as well as the dynamics of the flagellar motor. In this paper we study this model from an analytic point of view. By exploiting the separation of timescales observed in experiments, we show how to reduce the conformational spread model to a coarse-grained, cooperative binding model. We show that this simplified model reproduces very well the dynamics of the motor switch.

  9. From conformational spread to allosteric and cooperative models of E. coli flagellar motor

    Science.gov (United States)

    Pezzotta, A.; Adorisio, M.; Celani, A.

    2017-02-01

    Escherichia coli swims using flagella activated by rotary motors. The direction of rotation of the motors is indirectly regulated by the binding of a single messenger protein. The conformational spread model has been shown to accurately describe the equilibrium properties as well as the dynamics of the flagellar motor. In this paper we study this model from an analytic point of view. By exploiting the separation of timescales observed in experiments, we show how to reduce the conformational spread model to a coarse-grained, cooperative binding model. We show that this simplified model reproduces very well the dynamics of the motor switch.

  10. Motor-operated gearbox efficiency

    Energy Technology Data Exchange (ETDEWEB)

    DeWall, K.G.; Watkins, J.C.; Bramwell, D. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Weidenhamer, G.H.

    1996-12-01

    Researchers at the Idaho National Engineering Laboratory recently conducted tests investigating the operating efficiency of the power train (gearbox) in motor-operators typically used in nuclear power plants to power motor-operated valves. Actual efficiency ratios were determined from in-line measurements of electric motor torque (input to the operator gearbox) and valve stem torque (output from the gearbox) while the operators were subjected to gradually increasing loads until the electric motor stalled. The testing included parametric studies under reduced voltage and elevated temperature conditions. As part of the analysis of the results, the authors compared efficiency values determined from testing to the values published by the operator manufacturer and typically used by the industry in calculations for estimating motor-operator capabilities. The operators they tested under load ran at efficiencies lower than the running efficiency (typically 50%) published by the operator manufacturer.

  11. Piezoelectric wave motor

    Science.gov (United States)

    Yerganian, Simon Scott

    2001-07-17

    A piezoelectric motor having a stator in which piezoelectric elements are contained in slots formed in the stator transverse to the desired wave motion. When an electric field is imposed on the elements, deformation of the elements imposes a force perpendicular to the sides of the slot, deforming the stator. Appropriate frequency and phase shifting of the electric field will produce a wave in the stator and motion in a rotor. In a preferred aspect, the piezoelectric elements are configured so that deformation of the elements in direction of an imposed electric field, generally referred to as the d.sub.33 direction, is utilized to produce wave motion in the stator. In a further aspect, the elements are compressed into the slots so as to minimize tensile stresses on the elements in use.

  12. Permanent Magnet Boosted Modular Switched Reluctance Motor

    Directory of Open Access Journals (Sweden)

    SZABÓ Loránd

    2016-10-01

    Full Text Available This paper deals with the analyses of a novel motor structure obtained by boosting with permanent magnets a formerly studied modular switched reluctance motor. Upon dynamic simulation results the improvements of the proposed motor are emphasized.

  13. Engineering controllable bidirectional molecular motors based on myosin.

    Science.gov (United States)

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D; Parker, David; Bryant, Zev

    2012-02-19

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

  14. "Cargo-mooring" as an operating principle for molecular motors.

    Science.gov (United States)

    Lisowski, Bartosz; Kuśmierz, Łukasz; Żabicki, Michał; Bier, Martin

    2015-06-07

    Navigating through an ever-changing and unsteady environment, and utilizing chemical energy, molecular motors transport the cell׳s crucial components, such as organelles and vesicles filled with neurotransmitter. They generate force and pull cargo, as they literally walk along the polymeric tracks, e.g. microtubules. What we suggest in this paper is that the motor protein is not really pulling its load. The load is subject to diffusion and the motor may be doing little else than rectifying the fluctuations, i.e. ratcheting the load׳s diffusion. Below we present a detailed model to show how such ratcheting can quantitatively account for observed data. The consequence of such a mechanism is the dependence of the transport׳s speed and efficacy not only on the motor, but also on the cargo (especially its size) and on the environment (i.e. its viscosity and structure). Current experimental works rarely provide this type of information for in vivo studies. We suggest that even small differences between assays can impact the outcome. Our results agree with those obtained in wet laboratories and provide novel insight in a molecular motor׳s functioning.

  15. Noise characteristics of the Escherichia coli rotary motor

    Directory of Open Access Journals (Sweden)

    Clausznitzer Diana

    2011-09-01

    Full Text Available Abstract Background The chemotaxis pathway in the bacterium Escherichia coli allows cells to detect changes in external ligand concentration (e.g. nutrients. The pathway regulates the flagellated rotary motors and hence the cells' swimming behaviour, steering them towards more favourable environments. While the molecular components are well characterised, the motor behaviour measured by tethered cell experiments has been difficult to interpret. Results We study the effects of sensing and signalling noise on the motor behaviour. Specifically, we consider fluctuations stemming from ligand concentration, receptor switching between their signalling states, adaptation, modification of proteins by phosphorylation, and motor switching between its two rotational states. We develop a model which includes all signalling steps in the pathway, and discuss a simplified version, which captures the essential features of the full model. We find that the noise characteristics of the motor contain signatures from all these processes, albeit with varying magnitudes. Conclusions Our analysis allows us to address how cell-to-cell variation affects motor behaviour and the question of optimal pathway design. A similar comprehensive analysis can be applied to other two-component signalling pathways.

  16. Multiple-motor based transport and its regulation by Tau

    Science.gov (United States)

    Vershinin, Michael; Carter, Brian C.; Razafsky, David S.; King, Stephen J.; Gross, Steven P.

    2007-01-01

    Motor-based intracellular transport and its regulation are crucial to the functioning of a cell. Disruption of transport is linked to Alzheimer's and other neurodegenerative diseases. However, many fundamental aspects of transport are poorly understood. An important issue is how cells achieve and regulate efficient long-distance transport. Mounting evidence suggests that many in vivo cargoes are transported along microtubules by more than one motor, but we do not know how multiple motors work together or can be regulated. Here we first show that multiple kinesin motors, working in conjunction, can achieve very long distance transport and apply significantly larger forces without the need of additional factors. We then demonstrate in vitro that the important microtubule-associated protein, tau, regulates the number of engaged kinesin motors per cargo via its local concentration on microtubules. This function of tau provides a previously unappreciated mechanism to regulate transport. By reducing motor reattachment rates, tau affects cargo travel distance, motive force, and cargo dispersal. We also show that different isoforms of tau, at concentrations similar to those in cells, have dramatically different potency. These results provide a well defined mechanism for how altered tau isoform levels could impair transport and thereby lead to neurodegeneration without the need of any other pathway. PMID:17190808

  17. Single molecule energetics of F1-ATPase motor.

    Science.gov (United States)

    Muneyuki, Eiro; Watanabe-Nakayama, Takahiro; Suzuki, Tetsuya; Yoshida, Masasuke; Nishizaka, Takayuki; Noji, Hiroyuki

    2007-03-01

    Motor proteins are essential in life processes because they convert the free energy of ATP hydrolysis to mechanical work. However, the fundamental question on how they work when different amounts of free energy are released after ATP hydrolysis remains unanswered. To answer this question, it is essential to clarify how the stepping motion of a motor protein reflects the concentrations of ATP, ADP, and P(i) in its individual actions at a single molecule level. The F(1) portion of ATP synthase, also called F(1)-ATPase, is a rotary molecular motor in which the central gamma-subunit rotates against the alpha(3)beta(3) cylinder. The motor exhibits clear step motion at low ATP concentrations. The rotary action of this motor is processive and generates a high torque. These features are ideal for exploring the relationship between free energy input and mechanical work output, but there is a serious problem in that this motor is severely inhibited by ADP. In this study, we overcame this problem of ADP inhibition by introducing several mutations while retaining high enzymatic activity. Using a probe of attached beads, stepping rotation against viscous load was examined at a wide range of free energy values by changing the ADP concentration. The results showed that the apparent work of each individual step motion was not affected by the free energy of ATP hydrolysis, but the frequency of each individual step motion depended on the free energy. This is the first study that examined the stepping motion of a molecular motor at a single molecule level with simultaneous systematic control of DeltaG(ATP). The results imply that microscopically defined work at a single molecule level cannot be directly compared with macroscopically defined free energy input.

  18. Multimotor transport in a system of active and inactive kinesin-1 motors.

    Science.gov (United States)

    Scharrel, Lara; Ma, Rui; Schneider, René; Jülicher, Frank; Diez, Stefan

    2014-07-15

    Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action.

  19. Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Penelope J Boyd

    2017-04-01

    Full Text Available Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA, resulting from low levels of ubiquitously-expressed survival motor neuron (SMN protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant, gastrocnemius (intermediate vulnerability, and tibialis anterior (vulnerable muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1, was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1, rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo.

  20. Atypical motor neuron disease and related motor syndromes.

    Science.gov (United States)

    Verma, A; Bradley, W G

    2001-06-01

    There is an imperative need for the early diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) in the current era of emerging treatments. When evaluating the patient with ALS/MND, the neurologist must consider a number of other motor neuron disorders and related motor syndromes that may have clinical features resembling ALS/MND. The revised Airlie House-El Escorial diagnostic criteria have been established through the consensus of experts meeting at workshops. However, by definition, using these criteria a patient is likely to have fairly advanced disease at the time of a definitive ALS/MND diagnosis. The reasons for the difficulty in making an early ALS/MND diagnosis are several. No surrogate diagnostic marker currently exists for ALS/MND. ALS/MND at its onset is heterogeneous in clinical presentation, its clinical course is variable, and several clinical variants are recognized. In addition, certain motor syndromes, such as monomelic amyotrophy, postpolio muscular atrophy, and multifocal motor neuropathy, can clinically mimic ALS/MND. Therefore, not only may the diagnosis of ALS/MND be clinically missed in the early stages, but worse, the patient may be wrongly labeled as having ALS/MND. The diagnosis of ALS/MND requires a combination of upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Motor syndromes in which the deficit is restricted to the UMN or LMN through the entire course of the disease are described as atypical MND in this review. Approximately 5% of patients with ALS/MND have overt dementia with a characteristic frontal affect. ALS/MND with parkinsonism and dementia is rare outside the western Pacific region. The clinical course of motor disorder in these overlap syndromes does not differ from that in typical ALS/MND.

  1. Actions to promote energy efficient electric motors. Motors study group

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, A.T. de [Coimbra Univ. (PT). Inst. of Systems and Robotics (ISR)

    1996-10-01

    Motor electricity consumption is influenced by many factors including: motor efficiency, motor speed controls, power supply quality, harmonics, systems oversizing, distribution network, mechanical transmission system, maintenance practices, load management and cycling, and the efficiency of the end-use device (e.g. fan, pump, etc.). Due to their importance, an overview of these factors is presented in this report. This study also describes the electricity use in the industrial and tertiary sectors and the electricity consumption associated with the different types of electric motors systems in the Member States of the European Union, as well as estimated future evolution until 2010. The studies for individual countries were carried out by the different partners of the motors study group at a previous stage. The study has found that there is a lack of accurate information about the motor electricity consumption, installed motor capacity and the motor market in almost all the European Union countries and only some general statistical sources are available. There is little field data, which is mainly available in Denmark, France, Italy and the Netherlands. Due to this lack of primary information, some common assumptions were made, based on the experience of the members of the study group. This lack of end-use characterisation data shows the need for improvement from the point of view of current knowledge. It is therefore recommended that further research is undertaken to arrive at more accurate figures. These could be the basis for a better understanding for motor use in practice and - as a consequence - for a more precise appraisal of potentials and barriers to energy efficiency. (orig.)

  2. Correlations and Symmetry of Interactions Influence Collective Dynamics of Molecular Motors

    CERN Document Server

    Celis-Garza, Daniel; Kolomeisky, Anatoly B

    2015-01-01

    Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactions via thermodynamically consistent approach. We develop a new theoretical method that allows us to compute analytically all dynamic properties of the system. Our analysis shows that correlations play important role in dynamics of interacting molecular motors. Surprisingly, we find that the correlations for repulsive interactions are weaker and more short-range than the correlations for the attractive interactions. In ad...

  3. Remote control of myosin and kinesin motors using light-activated gearshifting.

    Science.gov (United States)

    Nakamura, Muneaki; Chen, Lu; Howes, Stuart C; Schindler, Tony D; Nogales, Eva; Bryant, Zev

    2014-09-01

    Cytoskeletal motors perform critical force generation and transport functions in eukaryotic cells. Engineered modifications of motor function provide direct tests of protein structure-function relationships and potential tools for controlling cellular processes or for harnessing molecular transport in artificial systems. Here, we report the design and characterization of a panel of cytoskeletal motors that reversibly change gears--speed up, slow down or switch directions--when exposed to blue light. Our genetically encoded structural designs incorporate a photoactive protein domain to enable light-dependent conformational changes in an engineered lever arm. Using in vitro motility assays, we demonstrate robust spatiotemporal control over motor function and characterize the kinetics of the optical gearshifting mechanism. We have used a modular approach to create optical gearshifting motors for both actin-based and microtubule-based transport.

  4. Conserved machinery of the bacterial flagellar motor.

    Science.gov (United States)

    Stahlberg, A; Schuster, S C; Bauer, M; Baeuerlein, E; Zhao, R; Reese, T S; Khan, S

    1995-04-01

    Novel periplasmic and cytoplasmic structural modules of the bases of bacterial flagella have been observed in situ and isolated using new biochemical protocols. Flagellar rotation may depend upon interactions of these modules with the intramembrane particle rings, a ubiquitous feature of flagellar bases necessary for torque generation. The outer membrane-associated basal disk of the Wolinella succinogenes polar flagellum has architecture well suited for interaction with the ring particles. However, antibody against the main W. succinogenes basal disk protein did not cross-react with flagella-enriched fractions from Salmonella typhimurium and Bacillus firmus; nor have such structures been observed in these species thus far. Antibodies against two S. typhimurium proteins, FliG and FliM, known to be involved in motor function and part of the cytoplasmic module in this species cross-reacted with flagella-enriched fractions from both W. succinogenes and B. firmus. In addition, flagellar cytoplasmic structure could be isolated from B. firmus. The basal disk may anchor the flagellar motor to the cell wall in some polar bacteria, but this does not seem to be a unique strategy. In contrast, the data indicate that the cytoplasmic module is conserved.

  5. Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease

    Directory of Open Access Journals (Sweden)

    Troakes Claire

    2011-03-01

    Full Text Available Abstract Background The cause of sporadic amyotrophic lateral sclerosis (ALS is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS. Results In motor neurons of homozygous symptomatic WR mice, a massive number of endosomal vesicles significantly enlarged (up to 3 μm in diameter were subjected to ultrastructural analysis and immunohistochemistry for the endosome-specific small GTPase protein Rab7 and for amyloid precursor protein (APP. Enlarged vesicles were neither detected in heterozygous WR nor in transgenic SOD1(G93A mice; in WR motor neurons, numerous APP/Rab7-positive vesicles were observed which were mostly LC3-negative, suggesting they are not autophagosomes. Conclusions We conclude that endosomal APP/Rab7 staining reflects impaired vesicle trafficking in WR mouse motor neurons. Based on these findings human ALS tissues were analysed for APP in enlarged vesicles and were detected in spinal cord motor neurons in six out of fourteen sporadic ALS cases. These enlarged vesicles were not detected in any of the familial ALS cases. Thus our study provides the first evidence for wobbler-like aetiologies in human ALS and suggests that the genes encoding proteins involved in vesicle trafficking should be screened for pathogenic mutations.

  6. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  7. Using AC Motors in Robotics

    Directory of Open Access Journals (Sweden)

    Hosein Marzi

    2008-11-01

    Full Text Available It has been proven that fuzzy controllers are capable of controlling non-linear systems where it is cumbersome to develop conventional controllers based on mathematical modeling. This paper describes designing fuzzy controllers for an AC motor run mechanism. It also compares performance of two controllers designed based on Mamdani and Takagi-Sugeno with the conventional control scheme in a short track length, following a high disturbance. Fine and rapid control of AC motors have been a challenge and the main obstacle in gaining popularity in use of AC motors in robots actuators. This chapter reviews how use of intelligent control scheme can help to solve this problem.

  8. Motor processes in mental rotation

    OpenAIRE

    Wexler, Mark; Kosslyn, Stephen; Berthoz, Alain

    1997-01-01

    Much indirect evidence supports the hypothesis that transformations of mental images are at least in part guided by motor processes, even in the case of images of abstract objects rather than of body parts. For example, rotation may be guided by processes that also prime one to see results of a specific motor action. We directly test the hypothesis by means of a dual-task paradigm in which subjects perform the Cooper-Shepard mental rotation task while executing an unseen motor rotation in a g...

  9. Distributed Stepping Motor Control System

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The beam diagnostic devices used at RIBLL are driven by stepper motors, which are controlled by I/O modules based on ISA-bus in an industrial computer. The disadvantages of such mode are that a large number of long cables are used and one computer to control is unsafe. We have developed a distributed stepping motor control system for the remote, local and centralized control of the stepping motors. RS-485 bus is used for the connection between the remote control unit and the local control units. The con...

  10. IC Design of Motor Ignitor

    Institute of Scientific and Technical Information of China (English)

    TANG Zheng-wei; ZHOU Zhong-qiang

    2008-01-01

    On the basis of analysing traditional motor ignitor, a new motor ignitor design with precise ignition angle control, consistency and low cost is proposed. Techniques of low pertinence to process and power supply are introduced to promote its stability, reliability and unity. This circuit is implemented with a standard CMOS technology with perfect electric static discharge(ESD) design and can work under a broad range of power supply from 3V~5V with a quiescent current less than 2mA and can be widely used in motor with a displacement of 125ml and below.

  11. Understanding motor acts and motor intentions in Williams syndrome.

    Science.gov (United States)

    Sparaci, Laura; Stefanini, Silvia; Marotta, Luigi; Vicari, Stefano; Rizzolatti, Giacomo

    2012-06-01

    Williams syndrome (WS) is a rare genetic disorder associated with unusually hyper-social demeanor and ease with strangers. These personality traits are accompanied by difficulties in social interactions, possibly related, at least in part, to a difficulty in understanding others' mental states. Studies on mentalizing capacities in individuals with WS have often led to contrasting results, some studies revealing specific impairments, others highlighting spared mentalizing capacities. So far, however, no study investigated the performance of individuals with WS in non-inferential understanding of others' motor intentions. In the present study we investigated this capacity by using a computer-based behavioral task using pictures of hand-object interactions. We asked individuals with WS first to describe what the other was doing (i.e. a task implying no kind of intention reading), and secondly, if successful in answering the first question, to describe the motor intention underlying the observed motor acts (i.e. why an act was being done, a task requiring non-inferential motor intention understanding). Results showed that individuals with WS made more errors in understanding what the other was doing (i.e. understanding a motor act) compared to both mental-age matched controls and chronological-age matched peers with typical development, while showing mental-age appropriate performance in understanding why an individual was acting (i.e. understanding a motor intention). These findings suggest novel perspectives for understanding impairments in social behavior in WS.

  12. Turn Motors Off When Not in Use - Motor Tip Sheet #10

    Energy Technology Data Exchange (ETDEWEB)

    None

    2008-07-01

    Motors use no energy when turned off. Reducing motor operating time by just 10% usually saves more energy than replacing a standard efficiency motor with a NEMA Premium® efficiency motor. In fact, given that 97% of the life cycle cost of purchasing and operating a motor is energy-related, turning a motor off 10% of the time could reduce energy costs enough to purchase three new motors.

  13. Statistical kinetics of processive molecular motors

    Science.gov (United States)

    Schnitzer, Mark Jacob

    1999-10-01

    We describe new theoretical and experimental tools for studying biological motor proteins at the single molecule scale. These tools enable measurements of molecular fuel economies, thereby providing insight into the pathways for conversion of biochemical energy into mechanical work. Kinesin is an ATP-dependent motor that moves processively along microtubules in discrete steps of 8 nm. How many molecules of ATP are hydrolysed per step? To determine this coupling ratio, we develop a fluctuation analysis, which relates the variance in records of mechanical displacement to the number of rate-limiting biochemical transitions in the engine cycle. Using fluctuation analysis and optical trapping interferometry, we determine that near zero load, single molecules of kinesin hydrolyse one ATP nucleotide per 8-nm step. To study kinesin behavior under load, we use a molecular force clamp, capable of maintaining constant loads on single kinesin motors moving processively. Analysis of records of motion under variable ATP concentrations and loads reveals that kinesin is a `tightly- coupled' motor, maintaining the 1:1 coupling ratio up to loads of ~ 5 pN. Moreover, a Michaelis-Menten analysis of velocity shows that the kinesin cycle contains at least two load- dependent transitions. The rate of one of these transitions affects ATP affinity, while the other does not. Therefore, the kinesin stall force must depend on the ATP concentration, as is demonstrated experimentally. These findings rule out existing theoretical models of kinesin motility. We develop a simple theoretical formalism describing a tightly-coupled mechanism for movement. This `energy-landscape' formalism quantitatively accounts for motile properties of RNA polymerase (RNAP), the enzyme that transcribes DNA into RNA. The shapes of RNAP force-velocity curves indicate that biochemical steps limiting transcription rates at low loads do not generate movement. Modeling suggests that high loads may halt RNAP by promoting a

  14. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

    Science.gov (United States)

    Voon, V; Brezing, C; Gallea, C; Hallett, M

    2014-01-01

    Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

  15. 75 FR 2923 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-01-19

    ... Federal Motor Carrier Safety Administration Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee Meeting. SUMMARY: FMCSA announces that its Motor Carrier Safety Advisory Committee (MCSAC)...

  16. 75 FR 72863 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-11-26

    ... Federal Motor Carrier Safety Administration Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration, DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee Meeting. SUMMARY: FMCSA announces that the Agency's Motor Carrier Safety Advisory Committee...

  17. 76 FR 12214 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2011-03-04

    ... Federal Motor Carrier Safety Administration Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration, DOT. ACTION: Notice: Announcement of Motor Carrier Safety Advisory Committee meeting; request for comment. SUMMARY: The Federal Motor Carrier Safety...

  18. 75 FR 29384 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-05-25

    ... Federal Motor Carrier Safety Administration Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee meeting. SUMMARY: FMCSA announces that its Motor Carrier Safety Advisory Committee (MCSAC)...

  19. High Temperature Bell Motor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The National Research Council (NRC) has identified the need for motors and actuators that can operate in extreme high and low temperature environments as a technical...

  20. Cryogenic Rotary Piezoelectric Motor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Piezoelectric motors operate on the principal of high frequency oscillation of high force precision ceramic elements. The high power oscillations are converted to...

  1. Annular Hybrid Rocket Motor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Engineers at SpaceDev have conducted a preliminary design and analysis of a proprietary annular design concept for a hybrid motor. A U.S. Patent application has been...

  2. Cryogenic Rotary Piezoelectric Motor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Piezoelectric motors operate on the principal of converting the high-frequency oscillation of high-force, precision ceramic elements into useful continuous motion....

  3. High-speed AC motors

    Energy Technology Data Exchange (ETDEWEB)

    Jokinen, T.; Arkkio, A. [Helsinki University of Technology Laboratory of Electromechanics, Otaniemi (Finland)

    1997-12-31

    The paper deals with various types of highspeed electric motors, and their limiting powers. Standard machines with laminated rotors can be utilised if the speed is moderate. The solid rotor construction makes it possible to reach higher power and speed levels than those of laminated rotors. The development work on high-speed motors done at Helsinki University of Technology is presented, too. (orig.) 12 refs.

  4. Electrical stimulation and motor recovery.

    Science.gov (United States)

    Young, Wise

    2015-01-01

    In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical

  5. Motor activity improves temporal expectancy.

    Directory of Open Access Journals (Sweden)

    Lilian Fautrelle

    Full Text Available Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1 pointing with a whole-body movement, (2 pointing only with the arm, (3 imagining pointing with a whole-body movement, (4 simply watching the stimulus presentation, (5 pointing with a whole-body movement in response to a target that appeared at irregular intervals (6 reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments.

  6. Forced desorption of semiflexible polymers, adsorbed and driven by molecular motors

    CERN Document Server

    Chaudhuri, Abhishek

    2014-01-01

    We formulate and characterize a model to describe dynamics of semiflexible polymers in the presence of activity due to motor proteins attached irreversibly to a substrate, and a transverse pulling force acting on one end of the filament. The stochastic binding-unbinding of the motor proteins and their ability to move along the polymer, generates active forces. As the pulling force reaches a threshold value, the polymer eventually desorbs from the substrate. We present a mean field theory that predicts increase in desorption force with polymer bending rigidity, active velocity and processivity of the motor proteins. Performing molecular dynamics simulations of the polymer in presence of a Langevin heat bath, and stochastic motor activity we obtain desorption phase diagrams that show good agreement with theory. With increase in pulling force, the polymer undergoes a first order phase transition from mostly adsorbed to fully desorbed state via a regime of coexistence where the steady state dynamics of the polyme...

  7. Estimation of physical parameters in induction motors

    DEFF Research Database (Denmark)

    Børsting, H.; Knudsen, Morten; Rasmussen, Henrik

    1994-01-01

    Parameter estimation in induction motors is a field of great interest, because accurate models are needed for robust dynamic control of induction motors......Parameter estimation in induction motors is a field of great interest, because accurate models are needed for robust dynamic control of induction motors...

  8. 30 CFR 18.34 - Motors.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Motors. 18.34 Section 18.34 Mineral Resources... PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.34 Motors. Explosion-proof electric motor assemblies intended for use in approved equipment in...

  9. 29 CFR 1926.601 - Motor vehicles.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Motor vehicles. 1926.601 Section 1926.601 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Motor Vehicles, Mechanized Equipment, and Marine Operations § 1926.601 Motor vehicles. (a) Coverage. Motor vehicles as covered by this part are those...

  10. Electric motor for laser-mechanical drilling

    Energy Technology Data Exchange (ETDEWEB)

    Grubb, Daryl L.; Faircloth, Brian O.; Zediker, Mark S.

    2017-10-10

    A high power laser drilling system utilizing an electric motor laser bottom hole assembly. A high power laser beam travels within the electric motor for performing a laser operation. A system includes a down hole electrical motor having a hollow rotor for conveying a high power laser beam having a wavelength less than 1060 nm through the electrical motor.

  11. Electric motor for laser-mechanical drilling

    Energy Technology Data Exchange (ETDEWEB)

    Grubb, Daryl L.; Faircloth, Brian O.; Zediker, Mark S.

    2015-07-07

    A high power laser drilling system utilizing an electric motor laser bottom hole assembly. A high power laser beam travels within the electric motor for advancing a borehole. High power laser drilling system includes a down hole electrical motor having a hollow rotor for conveying a high power laser beam through the electrical motor.

  12. Biophysics of filament length regulation by molecular motors

    CERN Document Server

    Kuan, Hui-Shun

    2013-01-01

    Regulating physical size is an essential problem that biological organisms must solve from the subcellular to the organismal scales, but it is not well understood what physical principles and mechanisms organisms use to sense and regulate their size. Any biophysical size-regulation scheme operates in a noisy environment and must be robust to other cellular dynamics and fluctuations. This work develops theory of filament length regulation inspired by recent experiments on kinesin-8 motor proteins, which move with directional bias on microtubule filaments and alter microtubule dynamics. Purified kinesin-8 motors can depolymerize chemically-stabilized microtubules. In the length-dependent depolymerization model, the rate of depolymerization tends to increase with filament length, because long filaments accumulate more motors at their tips and therefore shorten more quickly. When balanced with a constant filament growth rate, this mechanism can lead to a fixed polymer length. However, the mechanism by which kines...

  13. Biochemical physics modeling of biological nano-motors

    Energy Technology Data Exchange (ETDEWEB)

    Santamaría-Holek, I.; López-Alamilla, N. J. [UMDI-Facultad de Ciencias, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, 76230 Querétaro (Mexico)

    2014-01-14

    We present a biochemical physics model accounting for the dynamics and energetics of both translational and rotational protein motors. A modified version of the hand-over-hand mechanism considering competitive inhibition by ADP is presented. Transition state-like theory is used to reconstruct the time dependent free-energy landscape of the cycle catalyst process that allows to predicting the number of steps or rotations that a single motor can perform. In addition, following the usual approach of chemical kinetics, we calculate the average translational velocity and also the stopping time of processes involving a collectivity of motors, such as exocytosis and endocytosis processes. Finally, we formulate a stochastic model reproducing very well single realizations of kinesin and rotary ATPases.

  14. Control of non-conventional synchronous motors

    CERN Document Server

    Louis, Jean-Paul

    2013-01-01

    Classical synchronous motors are the most effective device to drive industrial production systems and robots with precision and rapidity. However, numerous applications require efficient controls in non-conventional situations. Firstly, this is the case with synchronous motors supplied by thyristor line-commutated inverters, or with synchronous motors with faults on one or several phases. Secondly, many drive systems use non-conventional motors such as polyphase (more than three phases) synchronous motors, synchronous motors with double excitation, permanent magnet linear synchronous motors,

  15. Teaching about operation of brushless DC motors

    OpenAIRE

    Čufar, Aleksandra

    2013-01-01

    Brush DC motor is being replaced by brushless DC motors on every area of application. My diploma thesis is a presentation of brushless DC motor, how it works and its application. Within first part we describe various electric motors and their application. There are several types of electric motors division. Last to be added is a brushless motor. Within second part of thesis we look into a brushless DC motor, how it works, its application and control. In the third part of thesis we construct a...

  16. Industrial electric motors; Moteurs electriques industriels

    Energy Technology Data Exchange (ETDEWEB)

    Maye, P.

    2005-08-15

    This book makes a synthesis of the present day knowledge on electric motors as main industrial applications of energy conversion. It explains the basic principles and the main physical laws controlling their operation. It describes with details the different types of motors with their utilization: the asynchronous motor (the most common AC motor), the synchronous motor with its 2 versions (winded for high powers and with magnets for high efficiency drives), the variable reluctance motor (promising and still under development), and the DC motor. (J.S.)

  17. 41 CFR 102-34.85 - What motor vehicles require motor vehicle identification?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What motor vehicles require motor vehicle identification? 102-34.85 Section 102-34.85 Public Contracts and Property Management... 34-MOTOR VEHICLE MANAGEMENT Identifying and Registering Motor Vehicles Motor Vehicle...

  18. Microtubules and associated molecular motors in Neurospora crassa.

    Science.gov (United States)

    Mouriño-Pérez, Rosa Reyna; Riquelme, Meritxell; Callejas-Negrete, Olga Alicia; Galván-Mendoza, José Iván

    2016-01-01

    The cytoskeleton provides structure, shape and movement to various cells. Microtubules (MTs) are tubular structures made of α and β-tubulin heterodimers organized in 13 protofilaments, forming a hollow cylinder. A vast group of MT-associated proteins determines the function, behavior and interaction of the MTs with other cellular components. Among these proteins, molecular motors such as the dynein-dynactin complex and kinesin superfamily play roles in MT organization and organelle transport. This article focuses on the MT cytoskeleton and associated molecular motors in the filamentous fungus Neurospora crassa In addition to reviewing current available information for this fungus and contrasting it with knowledge of other fungal species, we present new experimental results that support the role of dynein, dynactin and conventional kinesin in MT organization, dynamics and transport of subcellular structures (nuclei and secretory vesicles). In wild type hyphae of N. crassa, cytoplasmic MTs are arranged longitudinally along hyphae and display a helical curvature. They interlace with one another to form a network throughout the cytoplasm. N. crassa dynein and dynactin mutants have a scant and disorganized MT cytoskeleton, an erratic and reduced Spitzenkörper (Spk) and distorted hyphal morphology. In contrast, hyphae of mutants with defective conventional kinesin exhibit only minor disruptions in MT and Spk organization. Although nuclear positioning is affected in all mutants, the MT-associated motor proteins are not major contributors to nuclear movement during hyphal growth. Cytoplasmic bulk flow is the vehicle for nuclear displacement in growing hyphal regions of N. crassa Motors are involved in nuclei saltatory movements in both retrograde or anterograde direction. In the dynein and kinesin mutants, micro and macrovesicles can reach the Spk, although growth is slightly impaired and the Spk displays an erratic path. Hyphal growth requires MTs, and their associated

  19. Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.

    Science.gov (United States)

    Satriotomo, I; Nichols, N L; Dale, E A; Emery, A T; Dahlberg, J M; Mitchell, G S

    2016-05-13

    Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies.

  20. Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration.

    Science.gov (United States)

    Sopher, Bryce L; Thomas, Patrick S; LaFevre-Bernt, Michelle A; Holm, Ida E; Wilke, Scott A; Ware, Carol B; Jin, Lee-Way; Libby, Randell T; Ellerby, Lisa M; La Spada, Albert R

    2004-03-04

    X-linked spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder characterized by lower motor neuron degeneration. SBMA is caused by polyglutamine repeat expansions in the androgen receptor (AR). To determine the basis of AR polyglutamine neurotoxicity, we introduced human AR yeast artificial chromosomes carrying either 20 or 100 CAGs into mouse embryonic stem cells. The AR100 transgenic mice developed a late-onset, gradually progressive neuromuscular phenotype accompanied by motor neuron degeneration, indicating striking recapitulation of the human disease. We then tested the hypothesis that polyglutamine-expanded AR interferes with CREB binding protein (CBP)-mediated transcription of vascular endothelial growth factor (VEGF) and observed altered CBP-AR binding and VEGF reduction in AR100 mice. We found that mutant AR-induced death of motor neuron-like cells could be rescued by VEGF. Our results suggest that SBMA motor neuronopathy involves altered expression of VEGF, consistent with a role for VEGF as a neurotrophic/survival factor in motor neuron disease.

  1. Engineering of the fluorescent-energy-conversion arm of phi29 DNA packaging motor for single-molecule studies.

    Science.gov (United States)

    Lee, Tae Jin; Zhang, Hui; Chang, Chun-Li; Savran, Cagri; Guo, Peixuan

    2009-11-01

    The bacteriophage phi29 DNA packaging motor contains a protein core with a central channel comprising twelve copies of re-engineered gp10 protein geared by six copies of packaging RNA (pRNA) and a DNA packaging protein gp16 with unknown copies. Incorporation of this nanomotor into a nanodevice would be beneficial for many applications. To this end, extension and modification of the motor components are necessary for the linkage of this motor to other nanomachines. Here the re-engineering of the motor DNA packaging protein gp16 by extending its length and doubling its size using a fusion protein technique is reported. The modified motor integrated with the eGFP-gp16 maintains the ability to convert the chemical energy from adenosine triphosphate (ATP) hydrolysis to mechanical motion and package DNA. The resulting DNA-filled capsid is subsequently converted into an infectious virion. The extended part of the gp16 arm is a fluorescent protein eGFP, which serves as a marker for tracking the motor in single-molecule studies. The activity of the re-engineered motor with eGFP-gp16 is also observed directly with a bright-field microscope via its ability to transport a 2-microm-sized cargo bound to the DNA.

  2. 78 FR 77790 - Petition for Exemption From the Federal Motor Vehicle Theft Prevention Standard; General Motors...

    Science.gov (United States)

    2013-12-24

    ... National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Theft Prevention Standard; General Motors Corporation AGENCY: National Highway Traffic Safety Administration... full General Motors Corporation's (GM) petition for an exemption of the Cadillac SRX vehicle line...

  3. How does the motor relearning program improve neurological function of brain ischemia monkeys?

    Institute of Scientific and Technical Information of China (English)

    Yong Yin; Zhongtang Feng; Zhen Gu; Lei Pan; Lu Gan; Dongdong Qin; Bo Yang; Jin Guo; Xintian Hu; Tinghua Wang

    2013-01-01

    The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factorand basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia.

  4. Relative Contribution of Mutations in Genes for Autosomal Dominant Distal Hereditary Motor Neuropathies: A Genotype-Phenotype Correlation Study

    Science.gov (United States)

    Dierick, Ines; Baets, Jonathan; Irobi, Joy; Jacobs, An; De Vriendt, Els; Deconinck, Tine; Merlini, Luciano; Van den Bergh, Peter; Rasic, Vedrana Milic; Robberecht, Wim; Fischer, Dirk; Morales, Raul Juntas; Mitrovic, Zoran; Seeman, Pavel; Mazanec, Radim; Kochanski, Andrzej; Jordanova, Albena; Auer-Grumbach, Michaela; Helderman-van den Enden, A. T. J. M.; Wokke, John H. J.; Nelis, Eva; De Jonghe, Peter; Timmerman, Vincent

    2008-01-01

    Distal hereditary motor neuropathy (HMN) is a clinically and genetically heterogeneous group of disorders affecting spinal alpha-motor neurons. Since 2001, mutations in six different genes have been identified for autosomal dominant distal HMN; "glycyl-tRNA synthetase (GARS)," "dynactin 1 (DCTN1)," "small heat shock 27 kDa protein 1 (HSPB1),"…

  5. Motor Integrated Variable Speed Drives

    DEFF Research Database (Denmark)

    Singh, Yash Veer

    A new trend in the variable speed drives (VSDs) is to develop fully integrated systems, which lead to low-cost products with shorter design cycles. Motor Integrated design of VSDs will reduce cable length to connect drive with machine windings and installation time for end user. The electric drives...... are expected to have minimum effect on grid and motor connected to it, i.e. currents drawn from grid should be within specified limits and currents injecting in to machine should not overheat the machine windings to avoid insulation failure due to harmonics. It is also necessary that electric drives should...... when it comes to the development of any kind of power converter topology for power electronic applications. Concerning the use of a power converter in motor integrated VSDs, the first two mentioned aspects receive an even greater im-portance. Power converter design for integrated drives poses a host...

  6. Remote control for motor vehicle

    Science.gov (United States)

    Johnson, Dale R. (Inventor); Ciciora, John A. (Inventor)

    1984-01-01

    A remote controller is disclosed for controlling the throttle, brake and steering mechanism of a conventional motor vehicle, with the remote controller being particularly advantageous for use by severely handicapped individuals. The controller includes a remote manipulator which controls a plurality of actuators through interfacing electronics. The remote manipulator is a two-axis joystick which controls a pair of linear actuators and a rotary actuator, with the actuators being powered by electric motors to effect throttle, brake and steering control of a motor vehicle adapted to include the controller. The controller enables the driver to control the adapted vehicle from anywhere in the vehicle with one hand with minimal control force and range of motion. In addition, even though a conventional vehicle is adapted for use with the remote controller, the vehicle may still be operated in the normal manner.

  7. Cerebellum and Ocular Motor Control

    Directory of Open Access Journals (Sweden)

    Amir eKheradmand

    2011-09-01

    Full Text Available An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural-functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: 1 the flocculus/paraflocculus for high-frequency (brief vestibular responses, sustained pursuit eye movements and gaze-holding, 2 the nodulus/ventral uvula for low-frequency (sustained vestibular responses, and 3 the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region for saccades and pursuit initiation.

  8. Miniaturization of planar horn motors

    Science.gov (United States)

    Sherrit, Stewart; Ostlund, Patrick N.; Chang, Zensheu; Bao, Xiaoqi; Bar-Cohen, Yoseph; Widholm, Scott E.; Badescu, Mircea

    2012-04-01

    There is a great need for compact, efficient motors for driving various mechanisms including robots or mobility platforms. A study is currently underway to develop a new type of piezoelectric actuators with significantly more strength, low mass, small footprint, and efficiency. The actuators/motors utilize piezoelectric actuated horns which have a very high power density and high electromechanical conversion efficiency. The horns are fabricated using our recently developed novel pre-stress flexures that make them thermally stable and increases their coupling efficiency. The monolithic design and integrated flexures that pre-stresses the piezoelectric stack eliminates the use of a stress bolt. This design allows embedding solid-state motors and actuators in any structure so that the only macroscopically moving parts are the rotor or the linear translator. The developed actuator uses a stack/horn actuation and has a Barth motor configuration, which potentially generates very large torque and speeds that do not require gearing. Finite element modeling and design tools were investigated to determine the requirements and operation parameters and the results were used to design and fabricate a motor. This new design offers a highly promising actuation mechanism that can potentially be miniaturized and integrated into systems and structures. It can be configured in many shapes to operate as multi-degrees of freedom and multi-dimensional motors/actuators including unidirectional, bidirectional, 2D and 3D. In this manuscript, we are reporting the experimental measurements from a bench top design and the results from the efforts to miniaturize the design using 2×2×2 mm piezoelectric stacks integrated into thin plates that are of the order of 3 × 3 × 0.2 cm.

  9. Superconducting DC homopolar motors for ship propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Heiberger, M.; Reed, M.R.; Creedon, W.P.; O' Hea, B.J. [General Atomic (United States)

    2000-07-01

    Superconducting DC homopolar motors have undergone recent advances in technology, warranting serious consideration of their use for ship propulsion. Homopolar motor propulsion is now practical because of two key technology developments: cryogen-free superconducting refrigeration and high performance motor fiber brushes. These compact motors are ideal for podded applications, where reduced drag and fuel consumption are predicted. In addition, the simple DC motor controller is more efficient and reliable compared with AC motor controllers. Military ships also benefit from increased stealth implicit in homopolar DC excitation, which also allows the option for direct hull or pod mounting. (authors)

  10. [Treatment of multifocal motor neuropathies].

    Science.gov (United States)

    Azulay, J P; Pouget, J; Rihet, P; Serratrice, G

    1996-05-01

    Multifocal motor neuropathy is characterized by a progressive asymetrical weakness, predominantly affecting the upper limbs with persistent conduction blocks on motor but not sensory nerves. Treatment woth prednisone and plasma exchanges have failed to demonstrate any positive effects. Some improvements have been reported with cyclophosphamide. Mainly immunoglobulin therapy has been evaluated with a beneficial response in almost 70% of the cases. These benefits obtained over periods of less than six months have recently been confirmed by a long-term evaluation of 18 patients treated by repeated infusions.

  11. Homopolar motor with dual rotors

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, John S. (Oak Ridge, TN)

    1998-01-01

    A homopolar motor (10) has a field rotor (15) mounted on a frame (11) for rotation in a first rotational direction and for producing an electromagnetic field, and an armature rotor (17) mounted for rotation on said frame (11) within said electromagnetic field and in a second rotational direction counter to said first rotational direction of said field rotor (15). The two rotors (15, 17) are coupled through a 1:1 gearing mechanism (19), so as to travel at the same speed but in opposite directions. This doubles the output voltage and output power, as compared to a motor in which only the armature is rotated. Several embodiments are disclosed.

  12. Homopolar motor with dual rotors

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, J.S.

    1998-12-01

    A homopolar motor has a field rotor mounted on a frame for rotation in a first rotational direction and for producing an electromagnetic field, and an armature rotor mounted for rotation on said frame within said electromagnetic field and in a second rotational direction counter to said first rotational direction of said field rotor. The two rotors are coupled through a 1:1 gearing mechanism, so as to travel at the same speed but in opposite directions. This doubles the output voltage and output power, as compared to a motor in which only the armature is rotated. Several embodiments are disclosed. 7 figs.

  13. The Advanced Solid Rocket Motor

    Science.gov (United States)

    Mitchell, Royce E.

    1992-08-01

    The Advanced Solid Rocket Motor will utilize improved design features and automated manufacturing methods to produce an inherently safer propulsive system for the Space Shuttle and future launch systems. This second-generation motor will also provide an additional 12,000 pounds of payload to orbit, enhancing the utility and efficiency of the Shuttle system. The new plant will feature strip-wound, asbestos-free insulation; propellant continuous mixing and casting; and extensive robotic systems. Following a series of static tests at the Stennis Space Center, MS flights are targeted to begin in early 1997.

  14. The Advanced Solid Rocket Motor

    Science.gov (United States)

    Mitchell, Royce E.

    1992-01-01

    The Advanced Solid Rocket Motor will utilize improved design features and automated manufacturing methods to produce an inherently safer propulsive system for the Space Shuttle and future launch systems. This second-generation motor will also provide an additional 12,000 pounds of payload to orbit, enhancing the utility and efficiency of the Shuttle system. The new plant will feature strip-wound, asbestos-free insulation; propellant continuous mixing and casting; and extensive robotic systems. Following a series of static tests at the Stennis Space Center, MS flights are targeted to begin in early 1997.

  15. Motor motives. Gas motors and gas turbines in cogeneration stations

    Energy Technology Data Exchange (ETDEWEB)

    Hein, K.

    1987-04-01

    Gas turbines' attractivity is increasing. But despite the impressive efficiency of 50% the gas motor is not yet beaten. A steam process installed downstream of a piston engine boosts its mechanic efficiency, in the lower performance range these engines are peerless anyway.

  16. Interference in motor learning - is motor interference sensory?

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye; Petersen, Tue Hvass; Rothwell, John C

    mechanisms determine whether or not interference occurs. We hypothesised that interference requires the same neural circuits to be engaged in the two tasks and provoke competing processes of synaptic plasticity. To test this, subjects learned a ballistic ankle plantarflexion task. Early motor memory...

  17. Piezoelectric allostery of protein

    Science.gov (United States)

    Ohnuki, Jun; Sato, Takato; Takano, Mitsunori

    2016-07-01

    Allostery is indispensable for a protein to work, where a locally applied stimulus is transmitted to a distant part of the molecule. While the allostery due to chemical stimuli such as ligand binding has long been studied, the growing interest in mechanobiology prompts the study of the mechanically stimulated allostery, the physical mechanism of which has not been established. By molecular dynamics simulation of a motor protein myosin, we found that a locally applied mechanical stimulus induces electrostatic potential change at distant regions, just like the piezoelectricity. This novel allosteric mechanism, "piezoelectric allostery", should be of particularly high value for mechanosensor/transducer proteins.

  18. Chaperonopathies: spotlight on hereditary motor neuropathies

    Directory of Open Access Journals (Sweden)

    Vincenzo Lupo

    2016-12-01

    Full Text Available Distal hereditary motor neuropathies (dHMN comprise a group of rare hereditary neuromuscular disorders characterized by a peroneal muscular atrophy without sensory symptoms. To date twenty-three genes for dHMN have been reported and four of them encode for chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family, and HSPB1, HSPB3 and HSPB8, which encode three members of the family of small heat shock proteins. Except for HSPB1, with around thirty different mutations, the remaining three genes comprise a much low number of cases. Thus, only one case has been described caused by an HSPB3 mutation, whereas few DNAJB2 and HSPB8 cases are known, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the hot spot K141 residue of the HSPB8 chaperone. This low number of cases makes it difficult to understand the pathomechanism underlying the neuropathy. Chaperones can assemble in multi-chaperone complexes forming an integrative chaperone network in the cell, which plays relevant cellular roles in a variety of processes such as the correct folding of newly synthesized proteins, their escort to their precise cellular locations to form functional proteins and complexes and the response to protein misfolding, including the degradation of proteins that fail to refold properly. Despite of this variety of functions, mutations in some of them lead to diseases with a similar clinical picture, suggesting common pathways. This review gives an overview of the genetics of dHMNs caused by mutations in four genes, DNAJB2, HSPB1, HSPB3 and HSPB8, which encode chaperones and show a common disease mechanism.

  19. Motor Recovery of the Affected Hand in Subacute Stroke Correlates with Changes of Contralesional Cortical Hand Motor Representation

    OpenAIRE

    Jitka Veldema; Kathrin Bösl; Dennis Alexander Nowak

    2017-01-01

    Objective. To investigate the relationship between changes of cortical hand motor representation and motor recovery of the affected hand in subacute stroke. Methods. 17 patients with motor impairment of the affected hand were enrolled in an in-patient neurological rehabilitation program. Hand motor function tests (Wolf Motor Function Test, Action Research Arm Test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, motor map area size, motor map area volume,...

  20. Coupling with concentric contact around motor shaft for line start synchronous motor

    Energy Technology Data Exchange (ETDEWEB)

    Melfi, Michael J.; Burdeshaw, Galen E.

    2017-10-03

    A method comprises providing a line-start synchronous motor. The motor has a stator, a rotor core disposed within the stator, and a motor shaft. In accordance with a step of the method, a coupling for coupling a load to the motor is provided. The coupling has a motor shaft attachment portion configured to provide substantially concentric contact around the shaft at the end of the motor shaft. The coupling has a load attachment portion configured to operatively connect to a load. In accordance with a step of the method, a load is coupled to the motor with the coupling, and driven from start to at least near synchronous speed during steady state operation of the motor with a load coupled thereto. The motor shaft attachment portion may comprise a bushing assembly with matching and opposed tapered surfaces that cooperate to secure the motor shaft attachment portion around the motor shaft.

  1. Aversive stimuli exacerbate defensive motor behaviour in motor conversion disorder.

    Science.gov (United States)

    Blakemore, Rebekah L; Sinanaj, Indrit; Galli, Silvio; Aybek, Selma; Vuilleumier, Patrik

    2016-12-01

    Conversion disorder or functional neurological symptom disorder (FND) can affect the voluntary motor system, without an organic cause. Functional symptoms are thought to be generated unconsciously, arising from underlying psychological stressors. However, attempts to demonstrate a direct relationship between the limbic system and disrupted motor function in FND are lacking. We tested whether negative affect would exacerbate alterations of motor control and corresponding brain activations in individuals with FND. Ten patients and ten healthy controls produced an isometric precision-grip contraction at 10% of maximum force while either viewing visual feedback of their force output, or unpleasant or pleasant emotional images (without feedback). Force magnitude was continuously recorded together with change in brain activity using fMRI. For controls, force output decayed from the target level while viewing pleasant and unpleasant images. Patients however, maintained force at the target level without decay while viewing unpleasant images, indicating a pronounced effect of negative affect on force output in FND. This emotional modulation of force control was associated with different brain activation patterns between groups. Contrasting the unpleasant with the pleasant condition, controls showed increased activity in the inferior frontal cortex and pre-supplementary motor area, whereas patients had greater activity in the cerebellum (vermis), posterior cingulate cortex, and hippocampus. Engagement of a cerebellar-limbic network in patients is consistent with heightened processing of emotional salience, and supports the role of the cerebellum in freezing responses in the presence of aversive events. These data highlight a possible neural circuit through which psychological stressors elicit defensive behaviour and modulate motor function in FND. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Neurochemistry and the non-motor aspects of PD.

    Science.gov (United States)

    Ferrer, I; López-Gonzalez, I; Carmona, M; Dalfó, E; Pujol, A; Martínez, A

    2012-06-01

    Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficits and then worsen with disease progression. Although there is a relationship, albeit not causal, between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal α-synuclein, other neurological alterations are independent of the amount of α-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process. This may apply to complex alterations interfering with olfactory and autonomic nervous systemfunctions, emotions, sleep regulation, and behavioral, cognitive and mental performance. Involvement of the cerebral cortex leading to impaired behavior and cognition is related to several convergent altered factors including: a. dopaminergic, noradrenergic, serotoninergic and cholinergic cortical innervation; b. synapses; c. cortical metabolism; d. mitochondrial function and energy production; e. oxidative damage; f. transcription; g. protein expression; h. lipid composition; and i. ubiquitin–proteasome system and autophagy, among others. This complex situation indicates that multiple subcellular failure in selected cell populations is difficult to reconcilewith a reductionistic scenario of a single causative cascade of events leading to non-motor symptoms in PD. Furthermore, these alterationsmay appear at early stages of the disease and may precede the appearance of substantial irreversible cell loss by years. These observations have important implications in the design of therapeutic approaches geared to prevention and treatment of PD.

  3. Specificity of motor components in the dual flagellar system of Shewanella putrefaciens CN-32.

    Science.gov (United States)

    Bubendorfer, Sebastian; Held, Susanne; Windel, Natalie; Paulick, Anja; Klingl, Andreas; Thormann, Kai M

    2012-01-01

    Bacterial flagellar motors are intricate nanomachines in which the stator units and rotor component FliM may be dynamically exchanged during function. Similar to other bacterial species, the gammaproteobacterium Shewanella putrefaciens CN-32 possesses a complete secondary flagellar system along with a corresponding stator unit. Expression of the secondary system occurs during planktonic growth in complex media and leads to the formation of a subpopulation with one or more additional flagella at random positions in addition to the primary polar system. We used physiological and phenotypic characterizations of defined mutants in concert with fluorescent microscopy on labelled components of the two different systems, the stator proteins PomB and MotB, the rotor components FliM(1) and FliM(2), and the auxiliary motor components MotX and MotY, to determine localization, function and dynamics of the proteins in the flagellar motors. The results demonstrate that the polar flagellum is driven by a Na(+)-dependent FliM(1)/PomAB/MotX/MotY flagellar motor while the secondary system is rotated by a H(+)-dependent FliM(2)/MotAB motor. The components were highly specific for their corresponding motor and are unlikely to be extensively swapped or shared between the two flagellar systems under planktonic conditions. The results have implications for both specificity and dynamics of flagellar motor components. © 2011 Blackwell Publishing Ltd.

  4. Review on Modeling Molecular Motor%分子马达模型综述

    Institute of Scientific and Technical Information of China (English)

    王先菊; 艾保全; 刘良钢

    2001-01-01

    The structure and function of three kinds of motor proteins are introduced. The fundamental importance on studying molecular motor in living systems is also discribed. With detailed review on several archetype theoretical models, the progress and application on modeling molecule motor are presented.%介绍三类马达酶的结构,功能和生命体内分子马达的研究状况,并详细介绍几类典型分子马达的理论模型,同时展望了分子马达的发展前景和应用.

  5. Future challenges in single-molecule fluorescence and laser trap approaches to studies of molecular motors.

    Science.gov (United States)

    Elting, Mary Williard; Spudich, James A

    2012-12-11

    Single-molecule analysis is a powerful modern form of biochemistry, in which individual kinetic steps of a catalytic cycle of an enzyme can be explored in exquisite detail. Both single-molecule fluorescence and single-molecule force techniques have been widely used to characterize a number of protein systems. We focus here on molecular motors as a paradigm. We describe two areas where we expect to see exciting developments in the near future: first, characterizing the coupling of force production to chemical and mechanical changes in motors, and second, understanding how multiple motors work together in the environment of the cell.

  6. Technology and Motor Ability Development

    Science.gov (United States)

    Wang, Lin; Lang, Yong; Luo, Zhongmin

    2014-01-01

    As a new member joining the technology family, active video games have been developed to promote physical exercise. This working-in-progress paper shares an ongoing project on examining the basic motor abilities that are enhanced through participating in commercially available active video games. [For the full proceedings see ED557181.

  7. Motor interference in interactive contexts

    Directory of Open Access Journals (Sweden)

    Eris eChinellato

    2015-06-01

    Full Text Available Action observation and execution share overlapping neural substrates, so that simultaneous activation by observation and execution modulates motor performance. Previous literature on simple prehension tasks has revealed that motor influence can be two-sided: facilitation for observed and performed congruent actions and interference for incongruent actions. But little is known of the specific modulations of motor performance in complex forms of interaction. Is it possible that the very same observed movement can lead either to interference or facilitation effects on a temporally overlapping congruent executed action, depending on the context? To answer this question participants were asked to perform a reach-to-grasp movement adopting a precision grip (PG while: (i observing a fixation cross, (ii observing an actor performing a PG with interactive purposes, (iii observing an actor performing a PG without interactive purposes. In particular, in the interactive condition the actor was shown trying to pour some sugar on a large cup located out of her reach but close to the participant watching the video, thus eliciting in reaction a complementary whole-hand grasp. Notably, fine-grained kinematic analysis for this condition revealed a specific delay in the grasping and reaching components and an increased trajectory deviation despite the observed and executed movement’s congruency. Moreover, early peaks of trajectory deviation seem to indicate that socially relevant stimuli are acknowledged by the motor system very early. These data suggest that interactive contexts can determine a prompt modulation of stimulus–response compatibility effects.

  8. Treatment of functional motor disorders

    NARCIS (Netherlands)

    Gelauff, Jeannette M.; Dreissen, Yasmine E. M.; Tijssen, Marina A. J.; Stone, Jon

    2014-01-01

    OPINION STATEMENT: For the treatment of functional motor disorder, we recommend a three-stage approach. Firstly, patients must be assessed and given an unambiguous diagnosis, with an explanation that helps them understand that they have a genuine disorder, with the potential for reversibility. A key

  9. Imaging the ocular motor nerves.

    NARCIS (Netherlands)

    Ferreira, T.; Verbist, B.M.; Buchem, M. van; Osch, T. van; Webb, A.

    2010-01-01

    The ocular motor nerves (OMNs) comprise the oculomotor, trochlear and the abducens nerves. According to their course, they are divided into four or five anatomic segments: intra-axial, cisternal, cavernous and intra-orbital and, for the abducens nerve, an additional interdural segment. Magnetic reso

  10. Motor planning in congenital hemiplegia

    NARCIS (Netherlands)

    Steenbergen, B.; Verrel, J.; Gordon, A.M.

    2007-01-01

    Cerebral Palsy (CP) is a broad definition of a neurological condition in which disorders in movement execution and postural control limit the performance of activities of daily living. In this paper, we first review studies on motor planning in hemiplegic CP. Second, preliminary data of a recent

  11. Motor neurone disease: an overview.

    Science.gov (United States)

    Kent, Anna

    Motor neurone disease (MND) is a relatively rare, progressive and incurable neurological condition affecting patients' speech, mobility and respiratory function. Care of patients with MND is complex and involves various healthcare professionals and services. There is a need to discuss symptom management and promote palliative and end of life care from the point of diagnosis to ensure appropriate holistic care is provided.

  12. NASA's Advanced solid rocket motor

    Science.gov (United States)

    Mitchell, Royce E.

    The Advanced Solid Rocket Motor (ASRM) will not only bring increased safety, reliability and performance for the Space Shuttle Booster, it will enhance overall Shuttle safety by effectively eliminating 174 failure points in the Space Shuttle Main Engine throttling system and by reducing the exposure time to aborts due to main engine loss or shutdown. In some missions, the vulnerability time to Return-to-Launch Site aborts is halved. The ASRM uses case joints which will close or remain static under the effects of motor ignition and pressurization. The case itself is constructed of the weldable steel alloy HP 9-4-0.30, having very high strength and with superior fracture toughness and stress corrosion resistance. The internal insulation is strip-wound and is free of asbestos. The nozzle employs light weight ablative parts and is some 5,000 pounds lighter than the Shuttle motor used to date. The payload performance of the ASRM-powered Shuttle is 12,000 pounds higher than that provided by the present motor. This is of particular benefit for payloads delivered to higher inclinations and/or altitudes. The ASRM facility uses state-of-the-art manufacturing techniques, including continuous propellant mixing and direct casting.

  13. Putting Motor Resonance in Perspective

    Science.gov (United States)

    Lozano, Sandra C.; Hard, Bridgette Martin; Tversky, Barbara

    2008-01-01

    Perceiving another person's actions changes the spatial perspective people use to describe objects in a scene, possibly because seeing human action induces people to map the actions, including their spatial context, to their own body and motor representations [Lozano, S. C., Hard, B. M., & Tversky, B. (2007). Putting action in perspective.…

  14. Ironless-armature brushless motor

    Science.gov (United States)

    Fisher, R. L.

    1977-01-01

    Device uses 12-pole samarium cobalt permanent-magnet rotor and three Hall-effect sensors for commutation. In prototype motor, torque constant (3-phase delta) is 65 oz-in/amp; electrical time constant (L/R) is 0.2 x 0.001 sec, and armature resistance is 20 ohms.

  15. NASA's Advanced solid rocket motor

    Science.gov (United States)

    Mitchell, Royce E.

    1993-01-01

    The Advanced Solid Rocket Motor (ASRM) will not only bring increased safety, reliability and performance for the Space Shuttle Booster, it will enhance overall Shuttle safety by effectively eliminating 174 failure points in the Space Shuttle Main Engine throttling system and by reducing the exposure time to aborts due to main engine loss or shutdown. In some missions, the vulnerability time to Return-to-Launch Site aborts is halved. The ASRM uses case joints which will close or remain static under the effects of motor ignition and pressurization. The case itself is constructed of the weldable steel alloy HP 9-4-0.30, having very high strength and with superior fracture toughness and stress corrosion resistance. The internal insulation is strip-wound and is free of asbestos. The nozzle employs light weight ablative parts and is some 5,000 pounds lighter than the Shuttle motor used to date. The payload performance of the ASRM-powered Shuttle is 12,000 pounds higher than that provided by the present motor. This is of particular benefit for payloads delivered to higher inclinations and/or altitudes. The ASRM facility uses state-of-the-art manufacturing techniques, including continuous propellant mixing and direct casting.

  16. Motor planning in congenital hemiplegia

    NARCIS (Netherlands)

    Steenbergen, B.; Verrel, J.; Gordon, A.M.

    2007-01-01

    Cerebral Palsy (CP) is a broad definition of a neurological condition in which disorders in movement execution and postural control limit the performance of activities of daily living. In this paper, we first review studies on motor planning in hemiplegic CP. Second, preliminary data of a recent stu

  17. Fluctuation Relations for Molecular Motors

    Science.gov (United States)

    Lacoste, David; Mallick, Kirone

    This review is focused on the application of specific fluctuation relations, such as the Gallavotti-Cohen relation, to ratchet models of a molecular motor. A special emphasis is placed on two-state models such as the flashing ratchet model. We derive the Gallavotti-Cohen fluctuation relation for these models and we discuss some of its implications.

  18. Mechanical properties of organelles driven by microtubule-dependent molecular motors in living cells.

    Directory of Open Access Journals (Sweden)

    Luciana Bruno

    Full Text Available The organization of the cytoplasm is regulated by molecular motors which transport organelles and other cargoes along cytoskeleton tracks. Melanophores have pigment organelles or melanosomes that move along microtubules toward their minus and plus end by the action of cytoplasmic dynein and kinesin-2, respectively. In this work, we used single particle tracking to characterize the mechanical properties of motor-driven organelles during transport along microtubules. We tracked organelles with high temporal and spatial resolutions and characterized their dynamics perpendicular to the cytoskeleton track. The quantitative analysis of these data showed that the dynamics is due to a spring-like interaction between melanosomes and microtubules in a viscoelastic microenvironment. A model based on a generalized Langevin equation explained these observations and predicted that the stiffness measured for the motor complex acting as a linker between organelles and microtubules is ∼ one order smaller than that determined for motor proteins in vitro. This result suggests that other biomolecules involved in the interaction between motors and organelles contribute to the mechanical properties of the motor complex. We hypothesise that the high flexibility observed for the motor linker may be required to improve the efficiency of the transport driven by multiple copies of motor molecules.

  19. The nonlinear chemo-mechanic coupled dynamics of the F 1 -ATPase molecular motor.

    Science.gov (United States)

    Xu, Lizhong; Liu, Fang

    2012-03-01

    The ATP synthase consists of two opposing rotary motors, F0 and F1, coupled to each other. When the F1 motor is not coupled to the F0 motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F1-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F1-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F1-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F1 motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F1 motor, which increases the motor's rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F1 motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F1 motor and provide insight about the stochastic wave mechanics of F1-ATPase.

  20. Duty ratio of cooperative molecular motors.

    Science.gov (United States)

    Dharan, Nadiv; Farago, Oded

    2012-02-01

    Molecular motors are found throughout the cells of the human body and have many different and important roles. These micromachines move along filament tracks and have the ability to convert chemical energy into mechanical work that powers cellular motility. Different types of motors are characterized by different duty ratios, which is the fraction of time that a motor is attached to its filament. In the case of myosin II (a nonprocessive molecular machine with a low duty ratio), cooperativity between several motors is essential to induce motion along its actin filament track. In this work we use statistical mechanical tools to calculate the duty ratio of cooperative molecular motors. The model suggests that the effective duty ratio of nonprocessive motors that work in cooperation is lower than the duty ratio of the individual motors. The origin of this effect is the elastic tension that develops in the filament which is relieved when motors detach from the track.

  1. Chemistry: No turning back for motorized molecules

    Science.gov (United States)

    Clayden, Jonathan

    2016-06-01

    Two molecular motors have been developed that use chemical energy to drive rotational motion in a single direction. The findings bring the prospect of devices powered by such motors a tantalizing step closer. See Letter p.235

  2. Some typical solid propellant rocket motors

    NARCIS (Netherlands)

    Zandbergen, B.T.C.

    2013-01-01

    Typical Solid Propellant Rocket Motors (shortly referred to as Solid Rocket Motors; SRM's) are described with the purpose to form a database, which allows for comparative analysis and applications in practical SRM engineering.

  3. CDC Vital Signs: Motor Vehicle Crash Deaths

    Science.gov (United States)

    ... government is Tracking the nation’s progress in reducing crash injuries and deaths. www.cdc.gov/psr/national-summary/ ... Motor Vehicle Crash Deaths Vital Signs: Motor Vehicle Crash Injuries Vital Signs: Child Passenger Safety CDC: Child Passenger ...

  4. Some typical solid propellant rocket motors

    NARCIS (Netherlands)

    Zandbergen, B.T.C.

    2013-01-01

    Typical Solid Propellant Rocket Motors (shortly referred to as Solid Rocket Motors; SRM's) are described with the purpose to form a database, which allows for comparative analysis and applications in practical SRM engineering.

  5. Flux Tracking Control of Induction Motors

    Institute of Scientific and Technical Information of China (English)

    LanLin; XiaowuMu; ChunxiaBu

    2004-01-01

    This paper deals with flux tracking control of induction motors. Firstly,we analyze convergency of non-homogeneous linear time-varying systems and a sufficient condition is given. Finally, the flux regulator of induction motors is discussed.

  6. Molecular motors and their functions in plants

    Science.gov (United States)

    Reddy, A. S.

    2001-01-01

    Molecular motors that hydrolyze ATP and use the derived energy to generate force are involved in a variety of diverse cellular functions. Genetic, biochemical, and cellular localization data have implicated motors in a variety of functions such as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis, polarized growth, cell movements, spindle formation, chromosome movement, nuclear fusion, and signal transduction. In non-plant systems three families of molecular motors (kinesins, dyneins, and myosins) have been well characterized. These motors use microtubules (in the case of kinesines and dyneins) or actin filaments (in the case of myosins) as tracks to transport cargo materials intracellularly. During the last decade tremendous progress has been made in understanding the structure and function of various motors in animals. These studies are yielding interesting insights into the functions of molecular motors and the origin of different families of motors. Furthermore, the paradigm that motors bind cargo and move along cytoskeletal tracks does not explain the functions of some of the motors. Relatively little is known about the molecular motors and their roles in plants. In recent years, by using biochemical, cell biological, molecular, and genetic approaches a few molecular motors have been isolated and characterized from plants. These studies indicate that some of the motors in plants have novel features and regulatory mechanisms. The role of molecular motors in plant cell division, cell expansion, cytoplasmic streaming, cell-to-cell communication, membrane trafficking, and morphogenesis is beginning to be understood. Analyses of the Arabidopsis genome sequence database (51% of genome) with conserved motor domains of kinesin and myosin families indicates the presence of a large number (about 40) of molecular motors and the functions of many of these motors remain to be discovered. It is likely that many more motors with novel regulatory

  7. Some simple demonstration experiments involving homopolar motors

    OpenAIRE

    Stewart,Seán M.

    2007-01-01

    The ready availability of very strong permanent magnets in the form of rare-earth magnetic alloys such as neodymium-iron-boron has lead to renewed interest in one of the oldest types of electric motors - the homopolar motor. The ease with which a demonstration homopolar motor can now be built and operated when neodymium magnets are used is quite remarkable. In this paper some simple homopolar motors employing neodymium magnets suitable for demonstrational purposes are described and discussed.

  8. A new linear type hydraulic motor

    Science.gov (United States)

    Jiang, Dong; Zhang, Tong; Li, Wenhua; Chen, Xinyang

    2017-08-01

    This paper proposes the design of liner type hydraulic motor on the base of inner curved radial piston hydraulic motor. The hydraulic cylinders of the new type motor are in the straight line which will improve the utilization of the axial space and different out power can be supplied by changes the number of cylinders. In this paper, the structure and working principle of the liner type hydraulic motor is introduced.

  9. 77 FR 20558 - Federal Motor Vehicle Safety Standards; Platform Lifts for Motor Vehicles; Platform Lift...

    Science.gov (United States)

    2012-04-05

    ... National Highway Traffic Safety Administration 49 CFR Part 571 RIN 2127-AJ93 Federal Motor Vehicle Safety Standards; Platform Lifts for Motor Vehicles; Platform Lift Installations in Motor Vehicles AGENCY: National.... SUMMARY: This document adopts amendments to the Federal motor vehicle safety standards on platform...

  10. 78 FR 3081 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

    Science.gov (United States)

    2013-01-15

    ... National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Motor... Transportation (DOT). ACTION: Grant of petition for exemption. SUMMARY: This document grants in full Toyota Motor... to be as effective in reducing and deterring motor vehicle theft as compliance with the...

  11. 78 FR 4193 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Volvo

    Science.gov (United States)

    2013-01-18

    ... National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Motor... is likely to be as effective in reducing and deterring motor vehicle theft as compliance with the... the MY 2014 S60 vehicle line is effective in reducing and deterring motor vehicle theft. Volvo...

  12. 76 FR 12221 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

    Science.gov (United States)

    2011-03-04

    ... National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Motor... of Toyota Motor North America, Inc's., (Toyota) petition for an exemption of the Corolla vehicle line... equipment is likely to be as effective in reducing and deterring motor vehicle theft as compliance with...

  13. 77 FR 29752 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Jaguar...

    Science.gov (United States)

    2012-05-18

    ... Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Jaguar Land Rover... is likely to be as effective in reducing and deterring motor vehicle theft as compliance with the parts-marking requirements of the Federal Motor Vehicle Theft Prevention Standard, 49 CFR part...

  14. 77 FR 4396 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

    Science.gov (United States)

    2012-01-27

    ... National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Motor... full the petition of Toyota Motor North America, Inc's., (Toyota) petition for an exemption of the... the line as standard equipment is likely to be as effective in reducing and deterring motor...

  15. 76 FR 12220 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Jaguar...

    Science.gov (United States)

    2011-03-04

    ... National Highway Traffic Safety Administration Petition for Exemption From the Federal Motor Vehicle Motor... on the line as standard equipment is likely to be as effective in reducing and deterring motor... deterring motor vehicle theft as compliance with ] the parts-marking requirements of the Theft...

  16. 75 FR 49527 - General Motors Company Formerly Known as General Motors Corporation, Willow Run Transmission...

    Science.gov (United States)

    2010-08-13

    ..., Willow Run Transmission Plant Including On-Site Leased Workers From Aerotek; Ypsilanti, MI; Amended... General Motors Company, formerly known as General Motors Corporation, Willow Run Transmission Plant... location of General Motors Company, formerly known as General Motors Corporation, Willow Run...

  17. FUZZY LOGIC CONTROL OF ELECTRIC MOTORS AND MOTOR DRIVES: FEASIBILITY STUDY

    Science.gov (United States)

    The report gives results of a study (part 1) of fuzzy logic motor control (FLMC). The study included: 1) reviews of existing applications of fuzzy logic, of motor operation, and of motor control; 2) a description of motor control schemes that can utilize FLMC; 3) selection of a m...

  18. Assessment of Preschoolers' Gross Motor Proficiency: Revisiting Bruininks-Oseretsky Test of Motor Proficiency

    Science.gov (United States)

    Lam, Hazel Mei Yung

    2011-01-01

    Literature reveals that there are very few validated motor proficiency tests for young children. According to Gallahue and Ozmun, the Bruininks-Oseretsky Test of Motor Proficiency is a valid test. However, manipulative skills, which are classified as gross motor skills by most motor development specialists, are only tested in the Upper Limb…

  19. Neuronal mechanisms of motor learning and motor memory consolidation in healthy old adults

    NARCIS (Netherlands)

    Berghuis, K. M. M.; Veldman, M. P.; Solnik, S.; Koch, G.; Zijdewind, I.; Hortobagyi, T.

    2015-01-01

    It is controversial whether or not old adults are capable of learning new motor skills and consolidate the performance gains into motor memory in the offline period. The underlying neuronal mechanisms are equally unclear. We determined the magnitude of motor learning and motor memory consolidation i

  20. Linking molecular motors to membrane cargo

    NARCIS (Netherlands)

    A.S. Akhmanova (Anna); J.A. Hammer (John)

    2010-01-01

    textabstractThree types of motors, myosins, kinesins, and cytoplasmic dynein, cooperate to transport intracellular membrane organelles. Transport of each cargo is determined by recruitment of specific sets of motors and their regulation. Targeting of motors to membranes often depends on the formatio

  1. Electric Motor Thermal Management R&D

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin

    2016-06-07

    Thermal management enables more efficient and cost-effective motors. This Annual Merit Review presentation describes the technical accomplishments and progress in electric motor thermal management R&D over the last year. This project supports a broad industry demand for data, analysis methods, and experimental techniques to improve and better understand motor thermal management.

  2. 33 CFR 159.69 - Motor ratings.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Motor ratings. 159.69 Section 159.69 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.69 Motor ratings. Motors must be...

  3. 47 CFR 32.2112 - Motor vehicles.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Motor vehicles. 32.2112 Section 32.2112... FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.2112 Motor vehicles. This account shall include the original cost of motor vehicles of the type which are designed...

  4. 33 CFR 127.1311 - Motor vehicles.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Motor vehicles. 127.1311 Section... Waterfront Facilities Handling Liquefied Hazardous Gas Operations § 127.1311 Motor vehicles. (a) When LHG is... operator shall ensure that no person— (1) Stops or parks a motor vehicle in a space other than a...

  5. Motor Development Programming in Trisomic-21 Babies

    Science.gov (United States)

    Sanz, Teresa; Menendez, Javier; Rosique, Teresa

    2011-01-01

    The present study contributes to the understanding of gross motor development in babies with Down's syndrome. Also, it facilitates the comprehension of the efficiency of the early motor stimulation as well as of beginning it as early as possible. We worked with two groups of babies with Down's syndrome, beginning the early motor training in each…

  6. Motor Programming in Apraxia of Speech

    Science.gov (United States)

    Maas, Edwin; Robin, Donald A.; Wright, David L.; Ballard, Kirrie J.

    2008-01-01

    Apraxia of Speech (AOS) is an impairment of motor programming. However, the exact nature of this deficit remains unclear. The present study examined motor programming in AOS in the context of a recent two-stage model [Klapp, S. T. (1995). Motor response programming during simple and choice reaction time: The role of practice. "Journal of…

  7. Motor Proficiency Traits of Deaf Children.

    Science.gov (United States)

    Brunt, Denis; Broadhead, Geoffrey D.

    1982-01-01

    Children at the Louisiana State School for the Deaf were tested for motor proficiency using the Short Form of the Bruininks-Oseretsky Test of Motor Proficiency. The children appeared to lack balancing skills but scored better than hearing children in visual motor control. Sex and age differences are noted. (PP)

  8. Motor Control: The Heart of Kinesiology

    Science.gov (United States)

    Latash, Mark L.

    2008-01-01

    This brief review presents the subjective view of the author on the history of motor control and its current state among the subdisciplines of kinesiology. It summarizes the current controversies and challenges in motor control and emphasizes the necessity for an adequate set of notions that would make motor control (and kinesiology) a science.…

  9. Cognition and behavior in motor neuron disease

    NARCIS (Netherlands)

    Raaphorst, J.

    2015-01-01

    Motor neuron disease (MND) is a devastating neurodegenerative disorder characterized by progressive motor neuron loss, leading to weakness of the muscles of arms and legs, bulbar and respiratory muscles. Depending on the involvement of the lower and the upper motor neuron, amyotrophic lateral sclero

  10. Motor Development Programming in Trisomic-21 Babies

    Science.gov (United States)

    Sanz, Teresa; Menendez, Javier; Rosique, Teresa

    2011-01-01

    The present study contributes to the understanding of gross motor development in babies with Down's syndrome. Also, it facilitates the comprehension of the efficiency of the early motor stimulation as well as of beginning it as early as possible. We worked with two groups of babies with Down's syndrome, beginning the early motor training in each…

  11. [Non-motor symptoms of Parkinson's disease

    NARCIS (Netherlands)

    Weerkamp, N.J.; Nijhof, A.; Tissingh, G.

    2012-01-01

    Parkinson's disease has traditionally been viewed as a disease with only motor features. Nowadays, a wide variety of non-motor symptoms and signs are also recognised as being characteristic of the disease. Non-motor symptoms, most importantly autonomic dysfunction, neuropsychiatric symptoms and slee

  12. Motor Development: Manual of Alternative Procedures.

    Science.gov (United States)

    McCormack, James E.

    The manual of alternative procedures for teaching handicapped children focuses on programming, planning, and implementing training in the gross motor (posture, limb control, locomotion) and fine motor (facial, digital) skills. The manual consists of the following sections: specific teaching tactics commonly used in motor training stiuations…

  13. Unawareness of motor phenoconversion in Huntington disease.

    Science.gov (United States)

    McCusker, Elizabeth A; Gunn, David G; Epping, Eric A; Loy, Clement T; Radford, Kylie; Griffith, Jane; Mills, James A; Long, Jeffrey D; Paulsen, Jane S

    2013-09-24

    To determine whether Huntington disease (HD) mutation carriers have motor symptoms (complaints) when definite motor onset (motor phenoconversion) is diagnosed and document differences between the groups with and without unawareness of motor signs. We analyzed data from 550 HD mutation carriers participating in the multicenter PREDICT-HD Study followed through the HD prodrome. Data analysis included demographics, the Unified Huntington's Disease Rating Scale (UHDRS) and the Participant HD History of symptoms, self-report of progression, and cognitive, behavioral, and imaging measures. Unawareness was identified when no motor symptoms were self-reported but when definite motor HD was diagnosed. Of 38 (6.91%) with onset of motor HD, almost half (18/38 = 47.36%) had no motor symptoms despite signs of disease on the UHDRS motor rating and consistent with unawareness. A group with motor symptoms and signs was similar on a range of measures to the unaware group. Those with unawareness of HD signs reported less depression. Patients with symptoms had more striatal atrophy on imaging measures. Only half of the patients with newly diagnosed motor HD had motor symptoms. Unaware patients were less likely to be depressed. Self-report of symptoms may be inaccurate in HD at the earliest stage.

  14. Motor development in visually impaired children

    National Research Council Canada - National Science Library

    Hallemans, Ann

    2016-01-01

    ..., a visual impairment affects their overall development, including their motor development and skill acquisition. Different studies report a delay in gross motor milestones such as head control, sitting, standing, crawling, and walking during the first year of life. Vision appears to be key to normal postural and motor development in infants. W...

  15. Motor skill learning: age and augmented feedback

    NARCIS (Netherlands)

    Dijk, van Henk

    2006-01-01

    Learning motor skills is fundamental to human life. One of the most critical variables affecting motor learning, aside from practice itself, is augmented feedback (performance-related information). Although there is abundance of research on how young adults use augmented feedback to learn motor skil

  16. Motor Control: The Heart of Kinesiology

    Science.gov (United States)

    Latash, Mark L.

    2008-01-01

    This brief review presents the subjective view of the author on the history of motor control and its current state among the subdisciplines of kinesiology. It summarizes the current controversies and challenges in motor control and emphasizes the necessity for an adequate set of notions that would make motor control (and kinesiology) a science.…

  17. Random walks of cytoskeletal motors in open and closed compartments

    NARCIS (Netherlands)

    Lipowsky, R.; Klumpp, S.

    2001-01-01

    Random walks of molecular motors, which bind to and unbind from cytoskeletal filaments, are studied theoretically. The bound and unbound motors undergo directed and nondirected motion, respectively. Motors in open compartments exhibit anomalous drift velocities. Motors in closed compartments generat

  18. 78 FR 66801 - Motor Carrier Safety Advisory Committee; Charter Renewal

    Science.gov (United States)

    2013-11-06

    ... Federal Motor Carrier Safety Administration Motor Carrier Safety Advisory Committee; Charter Renewal AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Announcement of advisory... Committee that provides the Agency with advice and recommendations on motor carrier safety programs...

  19. Chaperonopathies: Spotlight on Hereditary Motor Neuropathies.

    Science.gov (United States)

    Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen

    2016-01-01

    Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8.

  20. Chaperonopathies: Spotlight on Hereditary Motor Neuropathies

    Science.gov (United States)

    Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen

    2016-01-01

    Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8. PMID:28018906

  1. High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss

    Directory of Open Access Journals (Sweden)

    Pereira Fred A

    2005-08-01

    Full Text Available Abstract Background Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3. Methods To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project. Results The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45. The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330. Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5. Conclusion These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in

  2. Traffic jams and shocks of molecular motors inside cellular protrusions.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2014-05-01

    Molecular motors are involved in key transport processes inside actin-based cellular protrusions. The motors carry cargo proteins to the protrusion tip which participate in regulating the actin polymerization and play a key role in facilitating the growth and formation of such protrusions. It is observed that the motors accumulate at the tips of cellular protrusions and form aggregates that are found to drift towards the protrusion base at the rate of actin treadmilling. We present a one-dimensional driven lattice model, where motors become inactive after delivering their cargo at the tip, or by loosing their cargo to a cargoless neighbor. The results suggest that the experimental observations may be explained by the formation of traffic jams that form at the tip. The model is solved using a novel application of mean-field and shock analysis. We find a new class of shocks that undergo intermittent collapses. Extensions with attachment and detachment events and relevance to experiments are briefly described.

  3. Anomalous motor mediated cargo transport in microtubule networks

    Science.gov (United States)

    Vandal, Steven; Macveigh-Fierro, Daniel; Shen, Zhiyuan; Lemoi, Kyle; Vidali, Luis; Ross, Jennifer; Tuzel, Erkan

    Cargo transport is an important biological mechanism by which cells locomote, self-organize, and actively transport organelles. This transport is mediated by the cytoskeletal network and molecular motors; however, it is not known how network self-organization and dynamics affect these transport processes. In order to develop a mechanistic understanding of cargo transport, we use a coarse-grained Brownian dynamics model that incorporates the dynamics of these networks, as well as experimentally determined motor properties. We will test these models with two experimental systems: (1) in vitro microtubule networks with kinesin-1 motors, and quantum dot cargos on recreated microtubule networks, and (2) an excellent model organism, the moss Physcomitrella patens, in which chloroplasts are transported via the microtubule network by means of kinesin-like proteins. Phenomenological network characterizations are made, both in vivo and in vitro, and cargo motility is characterized using Mean Squared Displacement (MSD) measurements. Our simulations shed light on the role of network density and motor properties on the observed transport behavior, and improve our understanding of cargo transport in cells.

  4. Traffic Jams and Shocks of Molecular Motors inside Cellular Protrusions

    CERN Document Server

    Pinkoviezky, Itai

    2013-01-01

    Molecular motors are involved in key transport processes inside actin-based cellular protrusions. The motors carry cargo proteins to the protrusion tip which participate in regulating the actin polymerization, and play a key role in facilitating the growth and formation of such protrusions. It is observed that the motors accumulate at the tips of cellular protrusions, and in addition form aggregates that are found to drift towards the protrusion base at the rate of actin treadmilling. We present a one-dimensional driven lattice model, where motors become inactive after delivering their cargo at the tip, or by loosing their cargo to a cargo-less neighbor. The results suggest that the experimental observations may be explained by the formation of traffic jams that form at the tip. The model is solved using a novel application of mean-field and shock analysis. We find a new class of shocks that undergo intermittent collapses, and on average do not obey the Rankine-Hugoniot relation.

  5. Stepper motor control that adjusts to motor loading

    Science.gov (United States)

    Howard, David E. (Inventor); Nola, Frank J. (Inventor)

    2000-01-01

    A system and method are provided for controlling a stepper motor having a rotor and a multi-phase stator. Sinusoidal command signals define a commanded position of the motor's rotor. An actual position of the rotor is sensed as a function of an electrical angle between the actual position and the commanded position. The actual position is defined by sinusoidal position signals. An adjustment signal is generated using the sinusoidal command signals and sinusoidal position signals. The adjustment signal is defined as a function of the cosine of the electrical angle. The adjustment signal is multiplied by each sinusoidal command signal to generate a corresponding set of excitation signals, each of which is applied to a corresponding phase of the multi-phase stator.

  6. Hereditary motor-sensory, motor, and sensory neuropathies in childhood.

    Science.gov (United States)

    Landrieu, Pierre; Baets, Jonathan; De Jonghe, Peter

    2013-01-01

    Hereditary neuropathies (HN) are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission, age of occurrence, and, in selected cases, pathological findings. The combination of these parameters frequently orients towards specific genetic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first pediatric concern. Primary, motor-sensory are the most frequent HN and are dominated by demyelinating AD forms (CMT1). Others are demyelinating AR forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Pure motor HN represent40 genes with various biological functions have been found responsible for HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait: for the pediatric neurologist, phenotype/genotype correlations constitute a permanent bidirectional exercise.

  7. Influence of direct motor-motor interaction in models for cargo transport by a single team of motors

    CERN Document Server

    Bouzat, Sebastian; 10.1088/1478-3975/7/4/046009

    2010-01-01

    We analyze theoretically the effects of excluded-volume interactions between motors on the dynamics of a cargo driven by multiple motors. The model considered shares many commons with other recently proposed in the literature, with the addition of direct interaction between motors and motor back steps. The cargo is assumed to follow a continuum Langevin dynamics, while individual motors evolve following a Monte Carlo algorithm based on experimentally accessible probabilities for discrete forward and backward jumps, and attachment and detachment rates. The links between cargo and motors are considered as non linear springs. By means of numerical simulations we compute the relevant quantities characterizing the dynamical properties of the system, and we compare the results to those for non interacting motors. We find that interactions lead to quite relevant changes in the force-velocity relation for cargo, with a considerable reduction of the stall force, and cause also a notable decrease of the run length. The...

  8. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  9. DEVELOPMENT OF FINE MOTOR COORDINATION AND VISUAL-MOTOR INTEGRATION IN PRESCHOOL CHILDREN

    OpenAIRE

    Haris MEMISEVIC; Selmir HADZIC

    2013-01-01

    Fine motor skills are prerequisite for many everyday activities and they are a good predictor of a child's later academic outcome. The goal of the present study was to assess the effects of age on the development of fine motor coordination and visual-motor integration in preschool children. The sample for this study consisted of 276 preschool children from Canton Sara­jevo, Bosnia and Herzegovina. We assessed children's motor skills with Beery Visual Motor Integration Test and Lafayette Pegbo...

  10. Method and apparatus for monitoring motor operated valve motor output torque and power at valve seating

    Science.gov (United States)

    Casada, Donald A.

    1996-01-01

    A method and apparatus are provided for monitoring a motor operated valve during the brief period when the valve seats and the torque switch trips to deenergize the valve motor. The method uses voltage measurements on the load side of a deenergizing switch that opens to deenergize the motor to determine, among other things, final motor rotational speed and the decelerating torque at motor deenergization.

  11. Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy

    OpenAIRE

    Swinny, J. D; van der Want, J.J.L.; Gramsbergen, A.

    2005-01-01

    The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spat...

  12. 78 FR 32223 - Control of Air Pollution From Motor Vehicles: Tier 3 Motor Vehicle Emission and Fuel Standards

    Science.gov (United States)

    2013-05-29

    ... Motor Vehicles: Tier 3 Motor Vehicle Emission and Fuel Standards AGENCY: Environmental Protection Agency... Pollution from Motor Vehicles: Tier 3 Motor Vehicle Emission and Fuel Standards'' (the proposed rule...

  13. 75 FR 47632 - New United Motor Manufacturing, Inc., Formerly a Joint Venture of General Motors Corporation and...

    Science.gov (United States)

    2010-08-06

    ... General Motors Corporation and Toyota Motor Corporation, Including On- Site Leased Workers From Corestaff, ABM Janitorial, Toyota Engineering and Manufacturing North America, NPA Coatings, Inc., and Premier... Motor Manufacturing, Inc., formerly a joint venture of General Motors Corporation and Toyota...

  14. 76 FR 10396 - New United Motor Manufacturing, Inc., Formerly a Joint Venture of General Motors Corporation and...

    Science.gov (United States)

    2011-02-24

    ... General Motors Corporation and Toyota Motor Corporation, Including On- Site Leased Workers From Corestaff, ABM Janitorial, Toyota Engineering and Manufacturing North America, NPA Coatings, Inc., Premier... of General Motors Corporation and Toyota Motor Corporation, including on-site leased workers...

  15. AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT XIX, LEARNING ABOUT CRANKING MOTORS.

    Science.gov (United States)

    Human Engineering Inst., Cleveland, OH.

    THIS MODULE OF A 25-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE OPERATING PRINCIPLES OF CRANKING MOTORS USED ON DIESEL POWERED EQUIPMENT, TOPICS ARE (1) CRANKING MOTORS. (2) MOTOR PINCIPLES, (3) CRANKING MOTOR CIRCUITS, (4) TYPES OF CRANKING MOTOR DRIVES, AND (5) CRANKING MOTOR SOLENOID CIRCUITS. THE MODULE CONSISTS OF A…

  16. Maximum power operation of interacting molecular motors

    DEFF Research Database (Denmark)

    Golubeva, Natalia; Imparato, Alberto

    2013-01-01

    We study the mechanical and thermodynamic properties of different traffic models for kinesin which are relevant in biological and experimental contexts. We find that motor-motor interactions play a fundamental role by enhancing the thermodynamic efficiency at maximum power of the motors......, as compared to the non-interacting system, in a wide range of biologically compatible scenarios. We furthermore consider the case where the motor-motor interaction directly affects the internal chemical cycle and investigate the effect on the system dynamics and thermodynamics....

  17. Ultrasonic Linear Motor with Anisotropic Composite

    Institute of Scientific and Technical Information of China (English)

    曾周末; 王新辉; 赵伯雷

    2004-01-01

    An idea to make up the vibrating body of ultrasonic motor with anisotropic composite is proposed and a linear piezoelectric motor is developed in this paper. Relative problems such as actuating mechanism, resonant frequency are discussed theoretically. According to the feature that impulse exists between the elastic body of composite ultrasonic linear motor and the base, an impulse analysis is presented to calculate the motor′s friction driving force and frictional conversion efficiency. The impulse analysis essentially explains the reason why the ultrasonic motor has great driving force, and can be applied to analyze the non-linear ultrasonic motor.

  18. Availability Analysis for High Voltage Synchronous Motor

    Institute of Scientific and Technical Information of China (English)

    DING Jin-hua; Erland Olsson; ZHOU Rong

    2004-01-01

    The operating experience data for 34 motors running for approximately 15 years in paper plants are collected. According to the data set, the reliability and availability characteristics of a highvoltage synchronous motor are analyzed based on the Markov Model. The unit or subsystem main rotor with windings in the motor system is more important for the motor system's availability, though its failure rate is lower compared to other units. Preventive maintenance is first introduced as a state in the markov Model for the motor system.

  19. Mathematical Modeling of Diaphragm Pneumatic Motors

    Directory of Open Access Journals (Sweden)

    Fojtášek Kamil

    2014-03-01

    Full Text Available Pneumatic diaphragm motors belong to the group of motors with elastic working parts. This part is usually made of rubber with a textile insert and it is deformed under the pressure of a compressed air or from the external mass load. This is resulting in a final working effect. In this type of motors are in contact two different elastic environments – the compressed air and the esaltic part. These motors are mainly the low-stroke and working with relatively large forces. This paper presents mathematical modeling static properties of diaphragm motors.

  20. Preconditioning crush increases the survival rate of motor neurons after spinal root avulsion

    Institute of Scientific and Technical Information of China (English)

    Lin Li; Yizhi Zuo; Jianwen He

    2014-01-01

    In a previous study, heat shock protein 27 was persistently upregulated in ventral motor neurons following nerve root avulsion or crush. Here, we examined whether the upregulation of heat shock protein 27 would increase the survival rate of motor neurons. Rats were divided into two groups:an avulsion-only group (avulsion of the L4 lumbar nerve root only) and a crush-avulsion group (the L4 lumbar nerve root was crushed 1 week prior to the avulsion). Immunofluores-cent staining revealed that the survival rate of motor neurons was significantly greater in the crush-avulsion group than in the avulsion-only group, and this difference remained for at least 5 weeks after avulsion. The higher neuronal survival rate may be explained by the upregulation of heat shock protein 27 expression in motor neurons in the crush-avulsion group. Further-more, preconditioning crush greatly attenuated the expression of nitric oxide synthase in the motor neurons. Our ifndings indicate that the neuroprotective action of preconditioning crush is mediated through the upregulation of heat shock protein 27 expression and the attenuation of neuronal nitric oxide synthase upregulation following avulsion.

  1. Motor-sensory confluence in tactile perception.

    Science.gov (United States)

    Saig, Avraham; Gordon, Goren; Assa, Eldad; Arieli, Amos; Ahissar, Ehud

    2012-10-03

    Perception involves motor control of sensory organs. However, the dynamics underlying emergence of perception from motor-sensory interactions are not yet known. Two extreme possibilities are as follows: (1) motor and sensory signals interact within an open-loop scheme in which motor signals determine sensory sampling but are not affected by sensory processing and (2) motor and sensory signals are affected by each other within a closed-loop scheme. We studied the scheme of motor-sensory interactions in humans using a novel object localization task that enabled monitoring the relevant overt motor and sensory variables. We found that motor variables were dynamically controlled within each perceptual trial, such that they gradually converged to steady values. Training on this task resulted in improvement in perceptual acuity, which was achieved solely by changes in motor variables, without any change in the acuity of sensory readout. The within-trial dynamics is captured by a hierarchical closed-loop model in which lower loops actively maintain constant sensory coding, and higher loops maintain constant sensory update flow. These findings demonstrate interchangeability of motor and sensory variables in perception, motor convergence during perception, and a consistent hierarchical closed-loop perceptual model.

  2. Online Monitoring of Induction Motors

    Energy Technology Data Exchange (ETDEWEB)

    McJunkin, Timothy R. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Lybeck, Nancy Jean [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-01-01

    The online monitoring of active components project, under the Advanced Instrumentation, Information, and Control Technologies Pathway of the Light Water Reactor Sustainability Program, researched diagnostic and prognostic models for alternating current induction motors (IM). Idaho National Laboratory (INL) worked with the Electric Power Research Institute (EPRI) to augment and revise the fault signatures previously implemented in the Asset Fault Signature Database of EPRI’s Fleet Wide Prognostic and Health Management (FW PHM) Suite software. Induction Motor diagnostic models were researched using the experimental data collected by Idaho State University. Prognostic models were explored in the set of literature and through a limited experiment with 40HP to seek the Remaining Useful Life Database of the FW PHM Suite.

  3. Motor for High Temperature Applications

    Science.gov (United States)

    Roopnarine (Inventor)

    2013-01-01

    A high temperature motor has a stator with poles formed by wire windings, and a rotor with magnetic poles on a rotor shaft positioned coaxially within the stator. The stator and rotor are built up from stacks of magnetic-alloy laminations. The stator windings are made of high temperature magnet wire insulated with a vitreous enamel film, and the wire windings are bonded together with ceramic binder. A thin-walled cylinder is positioned coaxially between the rotor and the stator to prevent debris from the stator windings from reaching the rotor. The stator windings are wound on wire spools made of ceramic, thereby avoiding need for mica insulation and epoxy/adhesive. The stator and rotor are encased in a stator housing with rear and front end caps, and rear and front bearings for the rotor shaft are mounted on external sides of the end caps to keep debris from the motor migrating into the bearings' races.

  4. Molecular Motors: Power Strokes Outperform Brownian Ratchets.

    Science.gov (United States)

    Wagoner, Jason A; Dill, Ken A

    2016-07-07

    Molecular motors convert chemical energy (typically from ATP hydrolysis) to directed motion and mechanical work. Their actions are often described in terms of "Power Stroke" (PS) and "Brownian Ratchet" (BR) mechanisms. Here, we use a transition-state model and stochastic thermodynamics to describe a range of mechanisms ranging from PS to BR. We incorporate this model into Hill's diagrammatic method to develop a comprehensive model of motor processivity that is simple but sufficiently general to capture the full range of behavior observed for molecular motors. We demonstrate that, under all conditions, PS motors are faster, more powerful, and more efficient at constant velocity than BR motors. We show that these differences are very large for simple motors but become inconsequential for complex motors with additional kinetic barrier steps.

  5. Locomotion of chemically powered autonomous nanowire motors

    Science.gov (United States)

    Wang, Lin; Li, Longqiu; Li, Tianlong; Zhang, Guangyu; Sun, Qian

    2015-08-01

    Physical insights on the hydrodynamics and locomotion of self-propelled nanowire motor under nonequilibrium steady state are investigated using finite element method in accordance with hybrid molecular dynamics/multiparticle collision dynamics and rigid body dynamics. Nanowire motor is discretized into finite segments, and forces of solvent molecule acting on the motor are assumed to be the sum of forces acting on all segments of the motor. We show that the locomotion of nanowire motor is mainly determined by the imbalance forces acting on the catalytic and noncatalytic segments. The average velocity along the axis increases significantly as a function of time prior to reaching equilibrium. The length of nanowire motor shows negligible effect on the velocity of the motor. Preliminary experimental results are provided to validate the current model.

  6. Effect of fuel concentration on cargo transport by a team of Kinesin motors

    Science.gov (United States)

    Takshak, Anjneya; Mishra, Nirvantosh; Kulkarni, Aditi; Kunwar, Ambarish

    2017-02-01

    Eukaryotic cells employ specialized proteins called molecular motors for transporting organelles and vesicles from one location to another in a regulated and directed manner. These molecular motors often work collectively in a team while transporting cargos. Molecular motors use cytoplasmic ATP as fuel, which is hydrolyzed to generate mechanical force. While the effect of ATP concentration on cargo transport by single Kinesin motor function is well understood, it is still unexplored, both theoretically and experimentally, how ATP concentration would affect cargo transport by a team of Kinesin motors. For instance, how does fuel concentration affect the travel distances and travel velocities of cargo? How cooperativity of Kinesin motors engaged on a cargo is affected by ATP concentration? To answer these questions, here we develop mechano-chemical models of cargo transport by a team of Kinesin motors. To develop these models we use experimentally-constrained mechano-chemical model of a single Kinesin motor as well as earlier developed mean-field and stochastic models of load sharing for cargo transport. Thus, our new models for cargo transport by a team of Kinesin motors include fuel concentration explicitly, which was not considered in earlier models. We make several interesting predictions which can be tested experimentally. For instance, the travel distances of cargos are very large at limited ATP concentrations in spite of very small travel velocity. Velocities of cargos driven by multiple Kinesin have a Michaelis-Menten dependence on ATP concentration. Similarly, cooperativity among the engaged Kinesin motors on the cargo shows a Michaelis-Menten type dependence, which attains a maximum value near physiological ATP concentrations. Our new results can be potentially useful in controlling artificial nano-molecular shuttles precisely for targeted delivery in various nano-technological applications.

  7. Non-viral gene therapy that targets motor neurons in vivo

    Directory of Open Access Journals (Sweden)

    Mary-Louise eRogers

    2014-10-01

    Full Text Available A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS. We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by ‘immunogene’ nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12 as DNA carrier was conjugated to an antibody (MLR2 to the neurotrophin receptor p75 (p75NTR. We used a plasmid (pVIVO2 designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP. MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0 % of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo.

  8. Mechanical transduction mechanisms of RecA-like molecular motors.

    Science.gov (United States)

    Liao, Jung-Chi

    2011-12-01

    A majority of ATP-dependent molecular motors are RecA-like proteins, performing diverse functions in biology. These RecA-like molecular motors consist of a highly conserved core containing the ATP-binding site. Here I examined how ATP binding within this core is coupled to the conformational changes of different RecA-like molecular motors. Conserved hydrogen bond networks and conformational changes revealed two major mechanical transduction mechanisms: (1) intra-domain conformational changes and (2) inter-domain conformational changes. The intra-domain mechanism has a significant hydrogen bond rearrangement within the domain containing the P-loop, causing relative motion between two parts of the protein. The inter-domain mechanism exhibits little conformational change in the P-loop domain. Instead, the major conformational change is observed between the P-loop domain and an adjacent domain or subunit containing the arginine finger. These differences in the mechanical transduction mechanisms may link to the underlying energy surface governing a Brownian ratchet or a power stroke.

  9. Advanced motor-controller development

    Science.gov (United States)

    Lesster, L. E.; Zeitlin, D. B.; Hall, W. B.

    1983-06-01

    The purpose of this development program was to investigate a promising alternative technique for control of a squirrel cage induction motor for subsea propulsion or hydraulic power applications. The technique uses microprocessor based generation of the pulse width modulation waveforms, which in turn permits use of a true integral volt-second pulse width control for the generation of low harmonic content sine waves from a 3 phase Graetz transistor power bridge.

  10. Motor memory in sports success

    Directory of Open Access Journals (Sweden)

    Silvia GRĂDINARU

    2017-02-01

    Full Text Available The model of modern sports performance asks for certain graduation in the treatment of its efficiency. Besides the coaching model, what matters is the genetic potential of the child or junior, and particularly the selection of the young talented athlete identified at the proper time and included in a proper training system, in full harmony with the education process. The sports output is determined by the simultaneous action of several factors whose influences are different. At present, there is a tendency to improve those factors on which rely sports outcomes and that need to be analysed and selected. Psychic capacity is a major factor, and mental control – the power to focus, motor intelligence, motor memory, creativity, and tactical skills play a major role in an athlete’s style. This study aims at showing the measure in which motor memory allows early and reliable diagnosis of future performance. The subjects selected are components of the mini-basket team of the Sports Club “Sport Star” from Timisoara, little girls that have played basketball since 1st grade in their free time (some of the girls have played it for four years. The research was carried out during a competitive year; we monitored the subjects both during coach lessons and minibasketball championship. To assess motor memory, we used the “cerebral module” consisting in memorising a complex of technical and tactical elements and applying them depending on the situation in the field. The research also involved monitoring the subjects in four directions considered defining in the assessment of the young athletes: somatic data, physical features, basketball features and intellectual potential. Most parameters point out a medium homogeneity of the group, except for height and commitment (great homogeneity. Half of the athletes of the tested group are above the mean of the group, which allows guiding them towards higher coaching forms (allowing them to practice basketball

  11. Electrostatic generator/motor configurations

    Science.gov (United States)

    Post, Richard F

    2014-02-04

    Electrostatic generators/motors designs are provided that generally may include a first cylindrical stator centered about a longitudinal axis; a second cylindrical stator centered about the axis, a first cylindrical rotor centered about the axis and located between the first cylindrical stator and the second cylindrical stator. The first cylindrical stator, the second cylindrical stator and the first cylindrical rotor may be concentrically aligned. A magnetic field having field lines about parallel with the longitudinal axis is provided.

  12. System and method for motor speed estimation of an electric motor

    Science.gov (United States)

    Lu, Bin [Kenosha, WI; Yan, Ting [Brookfield, WI; Luebke, Charles John [Sussex, WI; Sharma, Santosh Kumar [Viman Nagar, IN

    2012-06-19

    A system and method for a motor management system includes a computer readable storage medium and a processing unit. The processing unit configured to determine a voltage value of a voltage input to an alternating current (AC) motor, determine a frequency value of at least one of a voltage input and a current input to the AC motor, determine a load value from the AC motor, and access a set of motor nameplate data, where the set of motor nameplate data includes a rated power, a rated speed, a rated frequency, and a rated voltage of the AC motor. The processing unit is also configured to estimate a motor speed based on the voltage value, the frequency value, the load value, and the set of nameplate data and also store the motor speed on the computer readable storage medium.

  13. Foxp2 mutations impair auditory-motor association learning.

    Science.gov (United States)

    Kurt, Simone; Fisher, Simon E; Ehret, Günter

    2012-01-01

    Heterozygous mutations of the human FOXP2 transcription factor gene cause the best-described examples of monogenic speech and language disorders. Acquisition of proficient spoken language involves auditory-guided vocal learning, a specialized form of sensory-motor association learning. The impact of etiological Foxp2 mutations on learning of auditory-motor associations in mammals has not been determined yet. Here, we directly assess this type of learning using a newly developed conditioned avoidance paradigm in a shuttle-box for mice. We show striking deficits in mice heterozygous for either of two different Foxp2 mutations previously implicated in human speech disorders. Both mutations cause delays in acquiring new motor skills. The magnitude of impairments in association learning, however, depends on the nature of the mutation. Mice with a missense mutation in the DNA-binding domain are able to learn, but at a much slower rate than wild type animals, while mice carrying an early nonsense mutation learn very little. These results are consistent with expression of Foxp2 in distributed circuits of the cortex, striatum and cerebellum that are known to play key roles in acquisition of motor skills and sensory-motor association learning, and suggest differing in vivo effects for distinct variants of the Foxp2 protein. Given the importance of such networks for the acquisition of human spoken language, and the fact that similar mutations in human FOXP2 cause problems with speech development, this work opens up a new perspective on the use of mouse models for understanding pathways underlying speech and language disorders.

  14. Foxp2 mutations impair auditory-motor association learning.

    Directory of Open Access Journals (Sweden)

    Simone Kurt

    Full Text Available Heterozygous mutations of the human FOXP2 transcription factor gene cause the best-described examples of monogenic speech and language disorders. Acquisition of proficient spoken language involves auditory-guided vocal learning, a specialized form of sensory-motor association learning. The impact of etiological Foxp2 mutations on learning of auditory-motor associations in mammals has not been determined yet. Here, we directly assess this type of learning using a newly developed conditioned avoidance paradigm in a shuttle-box for mice. We show striking deficits in mice heterozygous for either of two different Foxp2 mutations previously implicated in human speech disorders. Both mutations cause delays in acquiring new motor skills. The magnitude of impairments in association learning, however, depends on the nature of the mutation. Mice with a missense mutation in the DNA-binding domain are able to learn, but at a much slower rate than wild type animals, while mice carrying an early nonsense mutation learn very little. These results are consistent with expression of Foxp2 in distributed circuits of the cortex, striatum and cerebellum that are known to play key roles in acquisition of motor skills and sensory-motor association learning, and suggest differing in vivo effects for distinct variants of the Foxp2 protein. Given the importance of such networks for the acquisition of human spoken language, and the fact that similar mutations in human FOXP2 cause problems with speech development, this work opens up a new perspective on the use of mouse models for understanding pathways underlying speech and language disorders.

  15. IPLEX administration improves motor neuron survival and ameliorates motor functions in a severe mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Murdocca, Michela; Malgieri, Arianna; Luchetti, Andrea; Saieva, Luciano; Dobrowolny, Gabriella; de Leonibus, Elvira; Filareto, Antonio; Quitadamo, Maria Chiara; Novelli, Giuseppe; Musarò, Antonio; Sangiuolo, Federica

    2012-09-25

    Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA.

  16. Splicing regulation of the Survival Motor Neuron genes and implications for treatment of spinal muscular atrophy

    OpenAIRE

    Bebee, Thomas W.; Gladman, Jordan T.; Chandler, Dawn S.

    2010-01-01

    Proximal spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of the survival motor neuron (SMN) protein. The reduced SMN levels are due to loss of the survival motor neuron-1 (SMN1) gene. Humans carry a nearly identical SMN2 gene that generates a truncated protein, due to a C to T nucleotide alteration in exon 7 that leads to inefficient RNA splicing of exon 7. This exclusion of SMN exon 7 is central to the onset of the SMA disease, however, this offers a unique ther...

  17. The influence of motor imagery on the learning of a fine hand motor skill.

    Science.gov (United States)

    Sobierajewicz, Jagna; Przekoracka-Krawczyk, Anna; Jaśkowski, Wojciech; Verwey, Willem B; van der Lubbe, Rob

    2017-01-01

    Motor imagery has been argued to affect the acquisition of motor skills. The present study examined the specificity of motor imagery on the learning of a fine hand motor skill by employing a modified discrete sequence production task: the Go/NoGo DSP task. After an informative cue, a response sequence had either to be executed, imagined, or withheld. To establish learning effects, the experiment was divided into a practice phase and a test phase. In the latter phase, we compared mean response times and accuracy during the execution of unfamiliar sequences, familiar imagined sequences, and familiar executed sequences. The electroencephalogram was measured in the practice phase to compare activity between motor imagery, motor execution, and a control condition in which responses should be withheld. Event-related potentials (ERPs) and event-related lateralizations (ERLs) showed strong similarities above cortical motor areas on trials requiring motor imagery and motor execution, while a major difference was found with trials on which the response sequence should be withheld. Behavioral results from the test phase showed that response times and accuracy improved after physical and mental practice relative to unfamiliar sequences (so-called sequence-specific learning effects), although the effect of motor learning by motor imagery was smaller than the effect of physical practice. These findings confirm that motor imagery also resembles motor execution in the case of a fine hand motor skill.

  18. Statistical determination of the step size of molecular motors

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, K C; Saleh, O A; Lionnet, T; Lia, G; Allemand, J-F; Bensimon, D; Croquette, V [Laboratoire de Physique Statistique, Ecole Normale Superieure, 24 rue Lhomond, Paris 75005 (France)

    2005-11-30

    Molecular motors are enzymatic proteins that couple the consumption of chemical energy to mechanical displacement. In order to elucidate the translocation mechanisms of these enzymes, it is of fundamental importance to measure the physical step size. The step size can, in certain instances, be directly measured with single-molecule techniques; however, in the majority of cases individual steps are masked by noise. The step size can nevertheless be obtained from noisy single-molecule records through statistical methods. This analysis is analogous to determining the charge of the electron from current shot noise. We review methods for obtaining the step size based on analysing, in both the time and frequency domains, the variance in position from noisy single-molecule records of motor displacement. Additionally, we demonstrate how similar methods may be applied to measure the step size in bulk kinetic experiments.

  19. GPNMB ameliorates mutant TDP-43-induced motor neuron cell death.

    Science.gov (United States)

    Nagahara, Yuki; Shimazawa, Masamitsu; Ohuchi, Kazuki; Ito, Junko; Takahashi, Hitoshi; Tsuruma, Kazuhiro; Kakita, Akiyoshi; Hara, Hideaki

    2017-08-01

    Glycoprotein nonmetastatic melanoma protein B (GPNMB) aggregates are observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, but the detailed localization is still unclear. Mutations of transactive response DNA binding protein 43kDa (TDP-43) are associated with neurodegenerative diseases including ALS. In this study, we evaluated the localization of GPNMB aggregates in the spinal cord of ALS patients and the effect of GPNMB against mutant TDP-43 induced motor neuron cell death. GPNMB aggregates were not localized in the glial fibrillary acidic protein (GFAP)-positive astrocyte and ionized calcium binding adaptor molecule-1 (Iba1)-positive microglia. GPNMB aggregates were localized in the microtubule-associated protein 2 (MAP-2)-positive neuron and neurofilament H non-phosphorylated (SMI-32)-positive neuron, and these were co-localized with TDP-43 aggregates in the spinal cord of ALS patients. Mock or TDP-43 (WT, M337V, and A315T) plasmids were transfected into mouse motor neuron cells (NSC34). The expression level of GPNMB was increased by transfection of mutant TDP-43 plasmids. Recombinant GPNMB ameliorated motor neuron cell death induced by transfection of mutant TDP-43 plasmids and serum-free stress. Furthermore, the expression of phosphorylated ERK1/2 and phosphorylated Akt were decreased by this stress, and these expressions were increased by recombinant GPNMB. These results indicate that GPNMB has protective effects against mutant TDP-43 stress via activating the ERK1/2 and Akt pathways, and GPNMB may be a therapeutic target for TDP-43 proteinopathy in familial and sporadic ALS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. The origin of minus-end directionality and mechanochemistry of Ncd motors.

    Directory of Open Access Journals (Sweden)

    Biman Jana

    Full Text Available Adaptation of molecular structure to the ligand chemistry and interaction with the cytoskeletal filament are key to understanding the mechanochemistry of molecular motors. Despite the striking structural similarity with kinesin-1, which moves towards plus-end, Ncd motors exhibit minus-end directionality on microtubules (MTs. Here, by employing a structure-based model of protein folding, we show that a simple repositioning of the neck-helix makes the dynamics of Ncd non-processive and minus-end directed as opposed to kinesin-1. Our computational model shows that Ncd in solution can have both symmetric and asymmetric conformations with disparate ADP binding affinity, also revealing that there is a strong correlation between distortion of motor head and decrease in ADP binding affinity in the asymmetric state. The nucleotide (NT free-ADP (φ-ADP state bound to MTs favors the symmetric conformation whose coiled-coil stalk points to the plus-end. Upon ATP binding, an enhanced flexibility near the head-neck junction region, which we have identified as the important structural element for directional motility, leads to reorienting the coiled-coil stalk towards the minus-end by stabilizing the asymmetric conformation. The minus-end directionality of the Ncd motor is a remarkable example that demonstrates how motor proteins in the kinesin superfamily diversify their functions by simply rearranging the structural elements peripheral to the catalytic motor head domain.

  1. How Is a Protein Molecule Nearsighted?

    Institute of Scientific and Technical Information of China (English)

    GAO De; JI Qing; L(U) Gang

    2005-01-01

    @@ The effect range of a local change of a protein molecule is calculated using a cluster method developed in this work based on the Gaussian software. This range is found to be about 8 A, which gives a concrete estimation on the "nearsightedness" by Kohn for protein molecules. The cluster method can be applied to calculation of the electronic density of a large molecule such as a motor protein and can provide a basis for the dynamical analysis of a single protein molecule.

  2. Stepping and crowding of molecular motors: statistical kinetics from an exclusion process perspective.

    Science.gov (United States)

    Ciandrini, Luca; Romano, M Carmen; Parmeggiani, Andrea

    2014-09-02

    Motor enzymes are remarkable molecular machines that use the energy derived from the hydrolysis of a nucleoside triphosphate to generate mechanical movement, achieved through different steps that constitute their kinetic cycle. These macromolecules, nowadays investigated with advanced experimental techniques to unveil their molecular mechanisms and the properties of their kinetic cycles, are implicated in many biological processes, ranging from biopolymerization (e.g., RNA polymerases and ribosomes) to intracellular transport (motor proteins such as kinesins or dyneins). Although the kinetics of individual motors is well studied on both theoretical and experimental grounds, the repercussions of their stepping cycle on the collective dynamics still remains unclear. Advances in this direction will improve our comprehension of transport process in the natural intracellular medium, where processive motor enzymes might operate in crowded conditions. In this work, we therefore extend contemporary statistical kinetic analysis to study collective transport phenomena of motors in terms of lattice gas models belonging to the exclusion process class. Via numerical simulations, we show how to interpret and use the randomness calculated from single particle trajectories in crowded conditions. Importantly, we also show that time fluctuations and non-Poissonian behavior are intrinsically related to spatial correlations and the emergence of large, but finite, clusters of comoving motors. The properties unveiled by our analysis have important biological implications on the collective transport characteristics of processive motor enzymes in crowded conditions.

  3. Self-organization of waves and pulse trains by molecular motors in cellular protrusions.

    Science.gov (United States)

    Yochelis, A; Ebrahim, S; Millis, B; Cui, R; Kachar, B; Naoz, M; Gov, N S

    2015-09-03

    Actin-based cellular protrusions are an ubiquitous feature of cells, performing a variety of critical functions ranging from cell-cell communication to cell motility. The formation and maintenance of these protrusions relies on the transport of proteins via myosin motors, to the protrusion tip. While tip-directed motion leads to accumulation of motors (and their molecular cargo) at the protrusion tip, it is observed that motors also form rearward moving, periodic and isolated aggregates. The origins and mechanisms of these aggregates, and whether they are important for the recycling of motors, remain open puzzles. Motivated by novel myosin-XV experiments, a mass conserving reaction-diffusion-advection model is proposed. The model incorporates a non-linear cooperative interaction between motors, which converts them between an active and an inactive state. Specifically, the type of aggregate formed (traveling waves or pulse-trains) is linked to the kinetics of motors at the protrusion tip which is introduced by a boundary condition. These pattern selection mechanisms are found not only to qualitatively agree with empirical observations but open new vistas to the transport phenomena by molecular motors in general.

  4. Using the motor to monitor pump conditions

    Energy Technology Data Exchange (ETDEWEB)

    Casada, D. [Oak Ridge National Lab., TN (United States)

    1996-12-01

    When the load of a mechanical device being driven by a motor changes, whether in response to changes in the overall process or changes in the performance of the driven device, the motor inherently responds. For induction motors, the current amplitude and phase angle change as the shaft load changes. By examining the details of these changes in amplitude and phase, load fluctuations of the driven device can be observed. The usefulness of the motor as a transducer to improve the understanding of devices with high torque fluctuations, such as positive displacement compressors and motor-operated valves, has been recognized and demonstrated for a number of years. On such devices as these, the spectrum of the motor current amplitude, phase, or power normally has certain characteristic peaks associated with various load components, such as the piston stroke or gear tooth meshing frequencies. Comparison and trending of the amplitudes of these peaks has been shown to provide some indication of their mechanical condition. For most centrifugal pumps, the load fluctuations are normally low in torque amplitude, and as a result, the motor experiences a correspondingly lower level of load fluctuation. However, both laboratory and field test data have demonstrated that the motor does provide insight into some important pump performance conditions, such as hydraulic stability and pump-to-motor alignment. Comparisons of other dynamic signals, such as vibration and pressure pulsation, to motor data for centrifugal pumps are provided. The effects of inadequate suction head, misalignment, mechanical and hydraulic unbalance on these signals are presented.

  5. Apraxia and motor dysfunction in corticobasal syndrome.

    Directory of Open Access Journals (Sweden)

    James R Burrell

    Full Text Available BACKGROUND: Corticobasal syndrome (CBS is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM, is associated with motor system dysfunction and limb apraxia in CBS. METHODS: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R, with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM. RESULTS: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices. CONCLUSIONS: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and

  6. Tokyo Motor Show 2003; Tokyo Motor Show 2003

    Energy Technology Data Exchange (ETDEWEB)

    Joly, E.

    2004-01-01

    The text which follows present the different techniques exposed during the 37. Tokyo Motor Show. The report points out the great tendencies of developments of the Japanese automobile industry. The hybrid electric-powered vehicles or those equipped with fuel cells have been highlighted by the Japanese manufacturers which allow considerable budgets in the research of less polluting vehicles. The exposed models, although being all different according to the manufacturer, use always a hybrid system: fuel cell/battery. The manufacturers have stressed too on the intelligent systems for navigation and safety as well as on the design and comfort. (O.M.)

  7. Balanced Activity of Three Mitotic Motors Is Required for Bipolar Spindle Assembly and Chromosome Segregation

    Directory of Open Access Journals (Sweden)

    Roy G.H.P. van Heesbeen

    2014-08-01

    Full Text Available Bipolar spindle assembly requires force to organize the microtubule network. Here, we show that three motor proteins, namely Eg5, Kif15, and dynein, act together to produce the right force balance in the spindle. Excessive inward force results in monopolar spindle formation, while excessive outward force generation results in unstable spindles with splayed spindle poles. Blocking activity of all three motors prevents bipolar spindle formation, but established bipolar spindles are refractory to loss of all motor activity. Further analysis shows that although these preformed spindles remain bipolar, outward force generation is required to establish sufficient tension on kinetochores and to accomplish successful chromosome segregation. Together, these results show how Eg5, Kif15, and dynein work together to build a bipolar spindle and reveal an important role for antagonistic motors in chromosome segregation.

  8. Tug-of-war between opposing molecular motors explains chromosomal oscillation during mitosis.

    Science.gov (United States)

    Sutradhar, S; Paul, R

    2014-03-07

    Chromosomes move towards and away from the centrosomes during the mitosis. This oscillation is observed when the kinetochore, a specific protein structure on the chromosome is captured by centrosome-nucleated polymer called microtubules. We present a computational model, incorporating activities of various molecular motors and microtubule dynamics, to demonstrate the observed oscillation. The model is robust and is not restricted to any particular cell type. Quantifying the average velocity, amplitude and periodicity of the chromosomal oscillation, we compare numerical results with the available experimental data. Our analysis supports a tug-of-war like mechanism between opposing motors that changes the course of chromosomal oscillation. It turns out that, various modes of oscillation can be fully understood by assembling the dynamics of molecular motors. Near the stall regime, when opposing motors are engaged in a tug-of-war, sufficiently large kinetochore-microtubule generated force may prolong the stall durations.

  9. Flagellar Motor Switching in Caulobacter Crescentus Obeys First Passage Time Statistics

    Science.gov (United States)

    Morse, Michael; Bell, Jordan; Li, Guanglai; Tang, Jay X.

    2015-11-01

    A Caulobacter crescentus swarmer cell is propelled by a helical flagellum, which is rotated by a motor at its base. The motor alternates between rotating in clockwise and counterclockwise directions and spends variable intervals of time in each state. We measure the distributions of these intervals for cells either free swimming or tethered to a glass slide. A peak time of around one second is observed in the distributions for both motor directions with counterclockwise intervals more sharply peaked and clockwise intervals displaying a larger tail at long times. We show that distributions of rotation intervals fit first passage time statistics for a biased random walker and the dynamic binding of CheY-P to FliM motor subunits accounts for this behavior. Our results also suggest that the presence of multiple CheY proteins in C. crescentus may be responsible for differences between its switching behavior and that of the extensively studied E. coli.

  10. Deletion of Nampt in Projection Neurons of Adult Mice Leads to Motor Dysfunction, Neurodegeneration, and Death

    Directory of Open Access Journals (Sweden)

    Xiaowan Wang

    2017-08-01

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT is the rate-limiting enzyme of the mammalian NAD+ biosynthesis salvage pathway. Using inducible and conditional knockout (cKO mice, we show that Nampt gene deletion in adult projection neurons leads to a progressive loss of body weight, hypothermia, motor neuron (MN degeneration, motor function deficits, paralysis, and death. Nampt deletion causes mitochondrial dysfunction, muscle fiber type conversion, and atrophy, as well as defective synaptic function at neuromuscular junctions (NMJs. When treated with nicotinamide mononucleotide (NMN, Nampt cKO mice exhibit reduced motor function deficits and prolonged lifespan. iNAMPT protein levels are significantly reduced in the spinal cord of amyotrophic lateral sclerosis (ALS patients, indicating the involvement of NAMPT in ALS pathology. Our findings reveal that neuronal NAMPT plays an essential role in mitochondrial bioenergetics, motor function, and survival. Our study suggests that the NAMPT-mediated NAD+ biosynthesis pathway is a potential therapeutic target for degenerative MN diseases.

  11. Reduction of power consumption in motor-driven applications by using PM motors; PM = Permanent Magnet; Reduktion af elforbrug til motordrift ved anvendelse af PM motorer

    Energy Technology Data Exchange (ETDEWEB)

    Hvenegaard, C.M.; Hansen, Mads P.R.; Groenborg Nikolaisen, C. (Teknologisk Institut, Taastrup (Denmark)); Nielsen, Sandie B. (Teknologisk Institut, AArhus (Denmark)); Ritchie, E.; Leban, K. (Aalborg Univ., Aalborg (Denmark))

    2009-12-15

    The traditional asynchronous motor with aluminum rotor is today by far the most widespread and sold electric motor, but a new and more energy efficient type of engine - the permanent magnet motor (PM motor) - is expected in the coming years to win larger and larger market shares. Several engine manufacturers in Europe, USA and Asia are now beginning to market the PM motors, which can replace the traditional asynchronous motor. The project aims to uncover the pros and cons of replacing asynchronous motors including EFF1 engines with PM motors, including the price difference. Furthermore, it is identified how the efficiency of PM motors is affected by low load levels and at various forms of control. Finally, the energy savings potential is analysed, by replacing asynchronous motors with PM motors. The study includes laboratory tests of PM motors, made in a test stand at Danish Technological Institute. (ln)

  12. Movement Sonification: Effects on Motor Learning beyond Rhythmic Adjustments

    OpenAIRE

    Alfred Oliver Effenberg; Ursula eFehse; Gerd eSchmitz; Bjoern eKrueger; Heinz eMechling

    2016-01-01

    Motor learning is based on motor perception and emergent perceptual-motor representations. A lot of behavioral research is related to single perceptual modalities, but during last two decades the contribution of multimodal perception on motor behavior was discovered more and more. A growing number of studies indicate an enhanced impact of multimodal stimuli on motor perception, motor control and motor learning in terms of better precision and higher reliability of the related actions. Behavio...

  13. Concurrent word generation and motor performance: further evidence for language-motor interaction.

    Directory of Open Access Journals (Sweden)

    Amy D Rodriguez

    Full Text Available Embodied/modality-specific theories of semantic memory propose that sensorimotor representations play an important role in perception and action. A large body of evidence supports the notion that concepts involving human motor action (i.e., semantic-motor representations are processed in both language and motor regions of the brain. However, most studies have focused on perceptual tasks, leaving unanswered questions about language-motor interaction during production tasks. Thus, we investigated the effects of shared semantic-motor representations on concurrent language and motor production tasks in healthy young adults, manipulating the semantic task (motor-related vs. nonmotor-related words and the motor task (i.e., standing still and finger-tapping. In Experiment 1 (n = 20, we demonstrated that motor-related word generation was sufficient to affect postural control. In Experiment 2 (n = 40, we demonstrated that motor-related word generation was sufficient to facilitate word generation and finger tapping. We conclude that engaging semantic-motor representations can have a reciprocal influence on motor and language production. Our study provides additional support for functional language-motor interaction, as well as embodied/modality-specific theories.

  14. Modification of motor cortex excitability during muscle relaxation in motor learning.

    Science.gov (United States)

    Sugawara, Kenichi; Tanabe, Shigeo; Suzuki, Tomotaka; Saitoh, Kei; Higashi, Toshio

    2016-01-01

    We postulated that gradual muscle relaxation during motor learning would dynamically change activity in the primary motor cortex (M1) and modify short-interval intracortical inhibition (SICI). Thus, we compared changes in M1 excitability both pre and post motor learning during gradual muscle relaxation. Thirteen healthy participants were asked to gradually relax their muscles from an isometric right wrist extension (30% maximum voluntary contraction; MVC) using a tracking task for motor learning. Single or paired transcranial magnetic stimulation (TMS) was applied at either 20% or 80% of the downward force output during muscle release from 30% MVC, and we compared the effects of motor learning immediately after the 1st and 10th blocks. Motor-evoked potentials (MEPs) from the extensor and flexor carpi radialis (ECR and FCR) were then measured and compared to evaluate their relationship before and after motor learning. In both muscles and each downward force output, motor cortex excitability during muscle relaxation was significantly increased following motor learning. In the ECR, the SICI in the 10th block was significantly increased during the 80% waveform decline compared to the SICI in the 1st block. In the FCR, the SICI also exhibited a greater inhibitory effect when muscle relaxation was terminated following motor learning. During motor training, acquisition of the ability to control muscle relaxation increased the SICI in both the ECR and FCR during motor termination. This finding aids in our understanding of the cortical mechanisms that underlie muscle relaxation during motor learning.

  15. Enhancement in motor learning through genetic manipulation of the Lynx1 gene.

    Directory of Open Access Journals (Sweden)

    Julie M Miwa

    Full Text Available The cholinergic system is a neuromodulatory neurotransmitter system involved in a variety of brain processes, including learning and memory, attention, and motor processes, among others. The influence of nicotinic acetylcholine receptors of the cholinergic system are moderated by lynx proteins, which are GPI-anchored membrane proteins forming tight associations with nicotinic receptors. Previous studies indicate lynx1 inhibits nicotinic receptor function and limits neuronal plasticity. We sought to investigate the mechanism of action of lynx1 on nicotinic receptor function, through the generation of lynx mouse models, expressing a soluble version of lynx and comparing results to the full length overexpression. Using rotarod as a test for motor learning, we found that expressing a secreted variant of lynx leads to motor learning enhancements whereas overexpression of full-length lynx had no effect. Further, adult lynx1KO mice demonstrated comparable motor learning enhancements as the soluble transgenic lines, whereas previously, aged lynx1KO mice showed performance augmentation only with nicotine treatment. From this we conclude the motor learning is more sensitive to loss of lynx function, and that the GPI anchor plays a role in the normal function of the lynx protein. In addition, our data suggests that the lynx gene plays a modulatory role in the brain during aging, and that a soluble version of lynx has potential as a tool for adjusting cholinergic-dependent plasticity and learning mechanisms in the brain.

  16. Nocturnal motor activity in a community sample.

    Science.gov (United States)

    Kronholm, E; Alanen, E; Hyyppä, M T

    1993-09-01

    The relationships between nocturnal motor activity and daytime psychophysiological activation were investigated in a random community sample of 199 subjects aged 35-55 years. Nocturnal motor activity was recorded with the static charge sensitive bed (SCSB, Bio-Matt). The association of nocturnal motor activity with demographic features, health status, laboratory blood values, afternoon electrodermal activity (EDA) and psychological distress was studied. A model for nocturnal motor activity was constructed and statistically analyzed. The analysis revealed that psychological distress, breathing disturbance, plasma glucose level and sympathetic activity were related significantly and independently to nocturnal motor activity. Their relations and the associations of sex, age, body mass index (BMI), sleep latency and health status with nocturnal motor activity were discussed in the context of the arousal theory of poor sleep.

  17. Non-motor features of Parkinson disease.

    Science.gov (United States)

    Schapira, Anthony H V; Chaudhuri, K Ray; Jenner, Peter

    2017-07-01

    Many of the motor symptoms of Parkinson disease (PD) can be preceded, sometimes for several years, by non-motor symptoms that include hyposmia, sleep disorders, depression and constipation. These non-motor features appear across the spectrum of patients with PD, including individuals with genetic causes of PD. The neuroanatomical and neuropharmacological bases of non-motor abnormalities in PD remain largely undefined. Here, we discuss recent advances that have helped to establish the presence, severity and effect on the quality of life of non-motor symptoms in PD, and the neuroanatomical and neuropharmacological mechanisms involved. We also discuss the potential for the non-motor features to define a prodrome that may enable the early diagnosis of PD.

  18. Error Sonification of a Complex Motor Task

    Directory of Open Access Journals (Sweden)

    Riener Robert

    2011-12-01

    Full Text Available Visual information is mainly used to master complex motor tasks. Thus, additional information providing augmented feedback should be displayed in other modalities than vision, e.g. hearing. The present work evaluated the potential of error sonification to enhance learning of a rowing-type motor task. In contrast to a control group receiving self-controlled terminal feedback, the experimental group could not significantly reduce spatial errors. Thus, motor learning was not enhanced by error sonification, although during the training the participant could benefit from it. It seems that the motor task was too slow, resulting in immediate corrections of the movement rather than in an internal representation of the general characteristics of the motor task. Therefore, further studies should elaborate the impact of error sonification when general characteristics of the motor tasks are already known.

  19. Environmental impact of used motor oil

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez-Duhalt, R.

    1989-02-01

    The information concerning the effects of used motor oil on the environment is reviewed. The production and fate of used motor oil are analyzed and the effects on soil and aquatic organisms are described. The combustion of waste crankcase oil, with particular reference to environmental impact, is discussed. The mutagenic and carcinogenic effects of used motor oil are described. Information on the biodegradation of lubricating motor oil is also reviewed. The available information shows that used motor oil is a very dangerous polluting product. As a consequence of its chemical composition, world-wide dispersion and effects on the environment, used motor oil must be considered a serious environmental problem. 3 tabs., 114 refs.

  20. Motor neurons and the sense of place.

    Science.gov (United States)

    Jessell, Thomas M; Sürmeli, Gülşen; Kelly, John S

    2011-11-03

    Seventy years ago George Romanes began to document the anatomical organization of the spinal motor system, uncovering a multilayered topographic plan that links the clustering and settling position of motor neurons to the spatial arrangement and biomechanical features of limb muscles. To this day, these findings have provided a structural foundation for analysis of the neural control of movement and serve as a guide for studies to explore mechanisms that direct the wiring of spinal motor circuits. In this brief essay we outline the core of Romanes's findings and place them in the context of recent studies that begin to provide insight into molecular programs that assign motor pool position and to resolve how motor neuron position shapes circuit assembly. Romanes's findings reveal how and why neuronal positioning contributes to sensory-motor connectivity and may have relevance to circuit organization in other regions of the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.