Sample records for activity spindle dynamics

  1. Dynamic Response Analysis of Motorized Spindle System

    ZHANG Li; LUO Yi-chao; XU Juan; XIAO Ru-feng; LI Xian-hui


    As to motorized spindle system, this paper builds a simplified 3D model of spindle and bearing, performs structure modal analysis, reveals its dynamic characteristics under the free model;furthermore, modifies bearing radial stiffness and number of model, and studies the change of modal parameters. On this basis, through the harmonic response analysis of the finite element model, dy-namic response characteristic caused by imbalance of monitored spindle system and law of vibration response to different amount of unbalance is analyzed.

  2. Measuring mitotic spindle dynamics in budding yeast

    Plumb, Kemp

    In order to carry out its life cycle and produce viable progeny through cell division, a cell must successfully coordinate and execute a number of complex processes with high fidelity, in an environment dominated by thermal noise. One important example of such a process is the assembly and positioning of the mitotic spindle prior to chromosome segregation. The mitotic spindle is a modular structure composed of two spindle pole bodies, separated in space and spanned by filamentous proteins called microtubules, along which the genetic material of the cell is held. The spindle is responsible for alignment and subsequent segregation of chromosomes into two equal parts; proper spindle positioning and timing ensure that genetic material is appropriately divided amongst mother and daughter cells. In this thesis, I describe fluorescence confocal microscopy and automated image analysis algorithms, which I have used to observe and analyze the real space dynamics of the mitotic spindle in budding yeast. The software can locate structures in three spatial dimensions and track their movement in time. By selecting fluorescent proteins which specifically label the spindle poles and cell periphery, mitotic spindle dynamics have been measured in a coordinate system relevant to the cell division. I describe how I have characterised the accuracy and precision of the algorithms by simulating fluorescence data for both spindle poles and the budding yeast cell surface. In this thesis I also describe the construction of a microfluidic apparatus that allows for the measurement of long time-scale dynamics of individual cells and the development of a cell population. The tools developed in this thesis work will facilitate in-depth quantitative analysis of the non-equilibrium processes in living cells.

  3. Simplified Dynamic Analysis of Grinders Spindle Node

    Demec, Peter


    The contribution deals with the simplified dynamic analysis of surface grinding machine spindle node. Dynamic analysis is based on the use of the transfer matrix method, which is essentially a matrix form of method of initial parameters. The advantage of the described method, despite the seemingly complex mathematical apparatus, is primarily, that it does not require for solve the problem of costly commercial software using finite element method. All calculations can be made for example in MS Excel, which is advantageous especially in the initial stages of constructing of spindle node for the rapid assessment of the suitability its design. After detailing the entire structure of spindle node is then also necessary to perform the refined dynamic analysis in the environment of FEM, which it requires the necessary skills and experience and it is therefore economically difficult. This work was developed within grant project KEGA No. 023TUKE-4/2012 Creation of a comprehensive educational - teaching material for the article Production technique using a combination of traditional and modern information technology and e-learning.

  4. Spindle activity phase-locked to sleep slow oscillations.

    Klinzing, Jens G; Mölle, Matthias; Weber, Frederik; Supp, Gernot; Hipp, Jörg F; Engel, Andreas K; Born, Jan


    The right hemisphere did not reveal any signs of a concurrent lateralization of spindle activity co-occurring with these SOs. Our data are consistent with the concept of the neocortical SO exerting top-down control over thalamic spindle generation. However, they call into question the notion that SOs locally coordinate spindles and thereby inform spindle-related memory processing. PMID:27103135

  5. Dynamic Analysis of Axial Magnetic Forces for DVD Spindle Motors


    The axial magnetic force, induced by the complicated flux linkage distribution from rotor magnet and stator slotted, is constructed by different relative heights and calculated by 3D finite element method (FEM) to analyze the dynamic characteristics for a DVD spindle motor. The axial magnetic force is designed to provide an axial stiffness and govern the natural frequency of the dynamic performance. According to the simulation results and experimental measurements, the dynamic behaviors are significantly improved with a variation of relative height of rotor magnet and stator slotted on a DVD spindle motor.

  6. A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis



    Full Text Available Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics and chromosome orientation and is frequently found overexpressed in human cancers. In this work, we show that Aurora-A interacts with the SUMO conjugating enzyme UBC9 and co-localizes with SUMO-1 in mitotic cells. Aurora-A can be SUMOylated in vitro and mutation in the highly conserved SUMOylation residue lysine 249 results in the induction of mitotic defects characterized by defective and multipolar spindles. The Aurora-AK249R mutant has normal kinase activity but it displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-AK249R mutant results in a significant increase in the susceptibility to malignant transformation induced by the Ras oncogene and an increased protection against apoptosis in tumor cells treated with mitotic poisons. These data suggest that modification by SUMO residues may control Aurora-A function at the spindle and suggest that deficient SUMOylation of this kinase may have relevant implications in tumor development or cancer therapy.

  7. Multi-frequency auditory stimulation disrupts spindling activity in anesthetized animals.

    Britvina, T; Eggermont, J J


    It is often implied that during the occurrence of spindle oscillations, thalamocortical neurons do not respond to signals from the outside world. Since recording of sound-evoked activity from cat auditory cortex is common during spindling this implies that sound stimulation changes the spindle-related brain state. Local field potentials and multi-unit activity recorded from cat primary auditory cortex under ketamine anesthesia during successive silence-stimulus-silence conditions were used to investigate the effect of sound on cortical spindle oscillations. Multi-frequency stimulation suppresses spindle waves, as shown by the decrease of spectral power within the spindle frequency range during stimulation as compared with the previous silent period. We show that the percentage suppression is independent of the power of the spindle waves during silence, and that the suppression of spindle power occurs very fast after stimulus onset. The global inter-spindle rhythm was not disturbed during stimulation. Spectrotemporal and correlation analysis revealed that beta waves (15-26 Hz), and to a lesser extent delta waves, were modulated by the same inter-spindle rhythm as spindle oscillations. The suppression of spindle power during stimulation had no effect on the spatial correlation of spindle waves. Firing rates increased under stimulation and spectro-temporal receptive fields could reliably be obtained. The possible mechanism of suppression of spindle waves is discussed and it is suggested that suppression likely occurs through activity of the specific auditory pathway. PMID:18164553

  8. Human Muscle Spindle Sensitivity Reflects the Balance of Activity between Antagonistic Muscles

    Dimitriou, Michael


    Muscle spindles are commonly considered as stretch receptors encoding movement, but the functional consequence of their efferent control has remained unclear. The "alpha-gamma coactivation" hypothesis states that activity in a muscle is positively related to the output of its spindle afferents. However, in addition to the above, possible reciprocal inhibition of spindle controllers entails a negative relationship between contractile activity in one muscle and spindle afferent output from its ...

  9. The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint

    Biggins, Sue; Murray, Andrew W.


    The spindle checkpoint prevents cell cycle progression in cells that have mitotic spindle defects. Although several spindle defects activate the spindle checkpoint, the exact nature of the primary signal is unknown. We have found that the budding yeast member of the Aurora protein kinase family, Ipl1p, is required to maintain a subset of spindle checkpoint arrests. Ipl1p is required to maintain the spindle checkpoint that is induced by overexpression of the protein kinase Mps1. Inactivating I...

  10. Dynamic characteristics of hard disk drive spindles supported by hydrodynamic bearings


    Most hard disk spindles currently used are supported by grease lubricated deep-groove ball bearings.However, in the trend of increasing spindle speed and reducing size and cost, the shortcomings of ball bearing spin-dles, such as high non-repeatable run out, high acoustic noise and short life time at high running speed, make themunsuitable for high performance hard disk drives (HDD). On the contrary, the dynamic characteristics of hydrody-namic bearing spindles are superior to that of ball bearing spindles. Therefore, they are considered to be the substi-tute of ball bearing spindles in HDD. In this paper, a simulative setup of HDD is build up. The dynamic characteristicsof liquid lubricated spiral groove bearing(SGB) spindles are studied. The effects of both operating condition andbearing clearance are investigated. It is found that running speed of the spindle has significant influence on its dy-namic performance, while the load has little influence. The effect of clearance is also evident.

  11. Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells

    Smith Charlotte M


    Full Text Available Abstract Background During metaphase clathrin stabilises the mitotic spindle kinetochore(K-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2™ is the first small molecule inhibitor of clathrin terminal domain and inhibits clathrin-mediated endocytosis. We investigated its effects on a second function for clathrin in mitosis. Results Pitstop 2 did not impair clathrin recruitment to the spindle but disrupted its function once stationed there. Pitstop 2 trapped HeLa cells in metaphase through loss of mitotic spindle integrity and activation of the spindle assembly checkpoint, phenocopying clathrin depletion and aurora A kinase inhibition. Conclusions Pitstop 2 is therefore a new tool for investigating clathrin spindle dynamics. Pitstop 2 reduced viability in dividing HeLa cells, without affecting dividing non-cancerous NIH3T3 cells, suggesting that clathrin is a possible novel anti-mitotic drug target.

  12. Microtubule Dynamics and Oscillating State for Mitotic Spindle

    Rashid-Shomali, Safura


    We present a physical mechanism that can cause the mitotic spindle to oscillate. The driving force for this mechanism emerges from the polymerization of astral microtubules interacting with the cell cortex. We show that Brownian ratchet model for growing microtubules reaching the cell cortex, mediate an effective mass to the spindle body and therefore force it to oscillate. We compare the predictions of this mechanism with the previous mechanisms which were based on the effects of motor proteins. Finally we combine the effects of microtubules polymerization and motor proteins, and present the detailed phase diagram for possible oscillating states.

  13. LIMK1 activity is required for MTOC localization and spindle bipolarity establishment during meiosis in mouse oocytes

    Liu Xiaoyun; Li Xin; Ma Wei


    Aneuploid embryo generally leads to infertility, spontaneous abortion and birth defects, mainly resulting from abnormal chromosome segregation during maternal oocytes meiosis. Chromosome division is conducted by bipolar spindle which formed through an acentrosomal way, dependent on a unique microtubule organizing center ( MTOC) in mammalian oocytes, however, the molecular composition and functional regulation of MTOC is still not fully ex-plored. LIM kinases 1 (LIMK1) is a conserved serine/threonine kinase, a major regulator of actin and microtubule dynamics, involved in microtubule stability and spindle positioning during mitosis. So far little is known about LIMK1 protein expression and its roles in oocytes during meiosis. We reported here the protein expression and sub-cellular distribution of LIMK1 in mouse oocytes during meiosis. Western blot procedure detected high and stable expression of LIMK1 in mouse oocytes from germinal vesicle ( GV) stage to metaphase II ( MII) . In contrast, acti-vated LIMK1 ( phosphorylated at Thr508 , pLIMK1 Thr508 ) was only observed after germinal vesicle breakdown ( GVBD) , and gradually increased with peak levels at metaphase I ( MI) and MII. Immunofluorescence analysis showed that LIMK1 was co-localized with microtubules on the whole spindle structure, while pLIMK1Thr508 was con- centrated with key components of MTOC,pericentrin and -Tubulin, on spindle poles in mouse oocytes. Inhibition of LIMK1 activity by BMS3, a specific ATPase competitive inhibitor, distroyed the formation of bipolar spindle structure, disturbed MTOC integrity and MTOC proteins recruitment to spindle poles. Moreover, LIMK1 inhibition caused chromosome misalignment and meiotic progression arrest at MI stage. Therefore, LIMK1 activity is required for formation and maintenance of bipolar spindle in mouse oocytes,importantly, pLIMK1T508 is MTOC-associated protein,involved in establishment and positioning of MTOC.

  14. Modelling muscle spindle dynamics for a proprioceptive prosthesis.

    Williams, Ian; Constandinou, Timothy G


    Muscle spindles are found throughout our skeletal muscle tissue and continuously provide us with a sense of our limbs' position and motion (proprioception). This paper advances a model for generating artificial muscle spindle signals for a prosthetic limb, with the aim of one day providing amputees with a sense of feeling in their artificial limb. By utilising the Opensim biomechanical modelling package the relationship between a joint's angle and the length of surrounding muscles is estimated for a prosthetic limb. This is then applied to the established Mileusnic model to determine the associated muscle spindle firing pattern. This complete system model is then reduced to allow for a computationally efficient hardware implementation. This reduction is achieved with minimal impact on accuracy by selecting key mono-articular muscles and fitting equations to relate joint angle to muscle length. Parameter values fitting the Mileusnic model to human spindles are then proposed and validated against previously published human neural recordings. Finally, a model for fusimotor signals is also proposed based on data previously recorded from reduced animal experiments. PMID:24110089

  15. Automated three-dimensional single cell phenotyping of spindle dynamics, cell shape, and volume

    Plumb, Kemp; Pelletier, Vincent; Kilfoil, Maria L


    We present feature finding and tracking algorithms in 3D in living cells, and demonstrate their utility to measure metrics important in cell biological processes. We developed a computational imaging hybrid approach that combines automated three-dimensional tracking of point-like features with surface determination from which cell (or nuclear) volume, shape, and planes of interest can be extracted. After validation, we applied the technique to real space context-rich dynamics of the mitotic spindle, and cell volume and its relationship to spindle length, in dividing living cells. These methods are additionally useful for automated segregation of pre-anaphase and anaphase spindle populations in budding yeast. We found that genetic deletion of the yeast kinesin-5 mitotic motor cin8 leads to large mother and daughter cells that were indistinguishable based on size, and that in those cells the spindle length becomes uncorrelated with cell size. The technique can be used to visualize and quantify tracked feature c...

  16. On the Free Vibration Modeling of Spindle Systems: A Calibrated Dynamic Stiffness Matrix

    Omar Gaber


    Full Text Available The effect of bearings on the vibrational behavior of machine tool spindles is investigated. This is done through the development of a calibrated dynamic stiffness matrix (CDSM method, where the bearings flexibility is represented by massless linear spring elements with tuneable stiffness. A dedicated MATLAB code is written to develop and to assemble the element stiffness matrices for the system’s multiple components and to apply the boundary conditions. The developed method is applied to an illustrative example of spindle system. When the spindle bearings are modeled as simply supported boundary conditions, the DSM model results in a fundamental frequency much higher than the system’s nominal value. The simply supported boundary conditions are then replaced by linear spring elements, and the spring constants are adjusted such that the resulting calibrated CDSM model leads to the nominal fundamental frequency of the spindle system. The spindle frequency results are also validated against the experimental data. The proposed method can be effectively applied to predict the vibration characteristics of spindle systems supported by bearings.

  17. Measurement Research of Motorized Spindle Dynamic Stiffness under High Speed Rotating

    Xiaopeng Wang


    Full Text Available High speed motorized spindle has become a key functional unit of high speed machine tools and effectively promotes the development of machine tool technology. The development of higher speed and more power puts forward the stricter requirement for the performance of motorized spindle, especially the dynamic performance which affects the machining accuracy, reliability, and production efficiency. To overcome the problems of ineffective loading and dynamic performance measurement of motorized spindle, a noncontact electromagnetic loading device is developed. The cutting load can be simulated by using electromagnetic force. A new method of measuring force by force sensors is presented, and the steady and transient loading force could be measured exactly. After the high speed machine spindle is tested, the frequency response curves of the spindle relative to machine table are collected at 0~12000 rpm; then the relationships between stiffness and speeds as well as between damping ratio and speeds are obtained. The result shows that not only the static and dynamic stiffness but also the damping ratio declined with the increase of speed.

  18. Spike Sorting of Muscle Spindle Afferent Nerve Activity Recorded with Thin-Film Intrafascicular Electrodes

    Milan Djilas; Christine Azevedo-Coste; David Guiraud; Ken Yoshida


    Afferent muscle spindle activity in response to passive muscle stretch was recorded in vivo using thin-film longitudinal intrafascicular electrodes. A neural spike detection and classification scheme was developed for the purpose of separating activity of primary and secondary muscle spindle afferents. The algorithm is based on the multiscale continuous wavelet transform using complex wavelets. The detection scheme outperforms the commonly used threshold detection, especially with recordings ...

  19. Using Photobleaching to Measure Spindle Microtubule Dynamics in Primary Cultures of Dividing Drosophila Meiotic Spermatocytes.

    Savoian, Matthew S


    In dividing animal cells, a microtubule (MT)-based bipolar spindle governs chromosome movement. Current models propose that the spindle facilitates and/or generates translocating forces by regionally depolymerizing the kinetochore fibers (k-fibers) that bind each chromosome. It is unclear how conserved these sites and the resultant chromosome-moving mechanisms are between different dividing cell types because of the technical challenges of quantitatively studying MTs in many specimens. In particular, our knowledge of MT kinetics during the sperm-producing male meiotic divisions remains in its infancy. In this study, I use an easy-to-implement photobleaching-based assay for measuring spindle MT dynamics in primary cultures of meiotic spermatocytes isolated from the fruit fly Drosophila melanogaster. By use of standard scanning confocal microscopy features, fiducial marks were photobleached on fluorescent protein (FP)-tagged MTs. These were followed by time-lapse imaging during different division stages, and their displacement rates were calculated using public domain software. I find that k-fibers continually shorten at their poles during metaphase and anaphase A through the process of MT flux. Anaphase chromosome movement is complemented by Pac-Man, the shortening of the k-fiber at its chromosomal interface. Thus, Drosophila spermatocytes share the sites of spindle dynamism and mechanisms of chromosome movement with mitotic cells. The data reveal the applicability of the photobleaching assay for measuring MT dynamics in primary cultures. This approach can be readily applied to other systems. PMID:25802491

  20. Neural networks with dynamical synapses: From mixed-mode oscillations and spindles to chaos

    Lee, K.; Goltsev, A. V.; Lopes, M. A.; Mendes, J. F. F.


    Understanding of short-term synaptic depression (STSD) and other forms of synaptic plasticity is a topical problem in neuroscience. Here we study the role of STSD in the formation of complex patterns of brain rhythms. We use a cortical circuit model of neural networks composed of irregular spiking excitatory and inhibitory neurons having type 1 and 2 excitability and stochastic dynamics. In the model, neurons form a sparsely connected network and their spontaneous activity is driven by random spikes representing synaptic noise. Using simulations and analytical calculations, we found that if the STSD is absent, the neural network shows either asynchronous behavior or regular network oscillations depending on the noise level. In networks with STSD, changing parameters of synaptic plasticity and the noise level, we observed transitions to complex patters of collective activity: mixed-mode and spindle oscillations, bursts of collective activity, and chaotic behavior. Interestingly, these patterns are stable in a certain range of the parameters and separated by critical boundaries. Thus, the parameters of synaptic plasticity can play a role of control parameters or switchers between different network states. However, changes of the parameters caused by a disease may lead to dramatic impairment of ongoing neural activity. We analyze the chaotic neural activity by use of the 0-1 test for chaos (Gottwald, G. & Melbourne, I., 2004) and show that it has a collective nature.

  1. Activity of spindle afferents from cat anterior thigh muscles. III. Effects of external stimuli.

    Loeb, G E; Hoffer, J A; Marks, W B


    Chronically implanted electrodes were used to record the activity of identified single muscle spindle afferents in awake cats during responses to various types of manual and electrical stimulation. During vigorous cyclical responses such as shaking and scratching, spindle afferents generally maintained at least some activity during both lengthening and shortening of the parent muscle, indicating that the programs for these movements include both extra- and intrafusal recruitment. During noncyclical responses such as ipsilateral limb withdrawal and crossed-extension, spindle activity was modest and poorly correlated with extrafusal activity. Weak cutaneous nerve shocks during walking elicited complex excitatory and inhibitory phase-dependent reflexes in the various muscles studied but caused relatively little change in spindle afferent activity, indicating a lack of correlation between alpha and gamma motoneuron activity. A primary and a secondary afferent from sartorius muscle were recorded simultaneously during walking cycles that were perturbed by electrically induced twitches of the antagonist hamstring muscles; both demonstrated highly sensitive, short latency responses to the resulting skeletal motion, consistent with their previously suggested roles in detecting small brief mechanical perturbations. The degree to which fusimotor responses were correlated with extrafusal responses to somatosensory perturbations was highly dependent on the specific nature of the stimulus and the response. Fusimotor reprogramming of the spindle sensitivity appears to be a feature of cyclical movements that are presumably under proprioceptive control, whereas brief perturbations within the context of a particular motor program may be ignored by the fusimotor system. PMID:2931503

  2. P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.

    Bompard, G; Rabeharivelo, G; Cau, J; Abrieu, A; Delsert, C; Morin, N


    The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2/M transition of the cell cycle. We have also identified that PAK4 regulates Ran GTPase activity during mitosis. Here, we show that after entering mitosis, PAK4-depleted cells maintain a prolonged metaphase-like state. In these cells, chromosome congression to the metaphase plate occurs with normal kinetics but is followed by an extended period during which membrane blebbing and spindle rotation are observed. These bipolar PAK4-depleted metaphase-like spindles have a defective astral microtubule (MT) network and are not centered in the cell but are in close contact with the cell cortex. As the metaphase-like state persists, centrosome fragmentation occurs, chromosomes scatter from the metaphase plate and move toward the spindle poles with an active spindle assembly checkpoint, a phenotype that is reminiscent of cohesion fatigue. PAK4 also regulates the acto-myosin cytoskeleton and we report that PAK4 depletion results in the induction of cortical membrane blebbing during prometaphase arrest. However, we show that membrane blebs, which are strongly enriched in phospho-cofilin, are not responsible for the poor anchoring of the spindle. As PAK4 depletion interferes with the localization of components of the dynein/dynactin complexes at the kinetochores and on the astral MTs, we propose that loss of PAK4 could induce a change in the activities of motor proteins. PMID:22450748

  3. Experimental Study on the Dynamic Performance of a New High-Speed Spindle Supported by Water-Lubricated Hybrid Bearings

    Lin Wang; Hua Xu


    The dynamic performance of a new high-speed spindle supported by water-lubricated hybrid bearings is experimentally studied on a test rig. The present design allows the speed of the spindle up to 30,000 rpm, with a bearing internal diameter of 40 mm, which makes it possible to simulate many actual machining processes. Some experiments have been presented to study the mechanical and thermal behaviors of the spindle and its supporting hybrid bearings. The maximum temperature rise is less than 1...

  4. Reduced Sleep Spindle Activity in Early-Onset and Elevated Risk for Depression

    Lopez, Jorge; Hoffmann, Robert; Armitage, Roseanne


    Objective: Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than…

  5. Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3 complex-driven cytoplasmic streaming in mouse oocytes

    Yi, Kexi; Unruh, Jay R.; Deng, Manqi; Slaughter, Brian D.; Rubinstein, Boris; Li, Rong


    Mature mammalian oocytes are poised for the completion of second polar body extrusion upon fertilization by positioning the metaphase spindle in close proximity to an actomyosin-rich cortical cap. Loss of this spindle position asymmetry is often associated with poor oocyte quality and infertility 1–3. Here, we report a novel role for the Arp2/3 actin nucleation complex in the maintenance of asymmetric spindle position in mature mouse oocytes. The Arp2/3 complex localizes to the cortical cap in a Ran GTPase-dependent manner and accounts for the nucleation of the majority of actin filaments in both the cortical cap and a cytoplasmic actin network. Inhibition of Arp2/3 complex activity or localization leads to rapid dissociation of the spindle from the cortex. High resolution live imaging and spatiotemporal image correlation spectroscopy (STICS) analysis reveal that in normal oocytes actin filaments flow continuously away from the Arp2/3-rich cortex, generating a cytoplamic streaming that results in a net pushing force on the spindle toward the actomyosin cap. Arp2/3 inhibition not only diminishes this actin flow and cytoplamic streaming but also enables a reverse streaming driven by myosin-II-based cortical contraction, leading to spindle movement away from the cortex. We conclude that the Arp2/3 complex maintains asymmetric meiotic spindle position by generating an actin polymerization-driven cytoplamic streaming and by suppressing a counteracting force from myosin-II-based contractility. PMID:21874009

  6. Central Spindle Self-Organization and Cytokinesis in Artificially Activated Sea Urchin Eggs.

    Henson, John H; Buckley, Mary W; Yeterian, Mesrob; Weeks, Richard M; Simerly, Calvin R; Shuster, Charles B


    The ability of microtubules of the mitotic apparatus to control the positioning and initiation of the cleavage furrow during cytokinesis was first established from studies on early echinoderm embryos. However, the identity of the microtubule population that imparts cytokinetic signaling is unclear. The two main--and not necessarily mutually exclusive--candidates are the central spindle and the astral rays. In the present study, we examined cytokinesis in ammonia-activated sea urchin eggs, which lack paternally derived centrosomes and undergo mitosis mediated by unusual anastral, bipolar mini-spindles. Live cell imaging and immunolabeling for microtubules and the centralspindlin constituent and kinesin-related protein, MKLP1, demonstrated that furrowing in ammonia-activated eggs was associated with aligned arrays of centralspindlin-linked, opposed bundles of antiparallel microtubules. These autonomous, zipper-like arrays were not associated with a mitotic apparatus, but did possess characteristics similar to the central spindle region of control, fertilized embryos. Our results highlight the self-organizing nature of the central spindle region and its ability to induce cytokinesis-like furrowing, even in the absence of a complete mitotic apparatus. PMID:27132131

  7. PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2.

    Hanafusa, Hiroshi; Kedashiro, Shin; Tezuka, Motohiro; Funatsu, Motoki; Usami, Satoshi; Toyoshima, Fumiko; Matsumoto, Kunihiro


    Correct formation of the cell division axis requires the initial precise orientation of the mitotic spindle. Proper spindle orientation depends on centrosome maturation, and Polo-like kinase 1 (PLK1) is known to play a crucial role in this process. However, the molecular mechanisms that function downstream of PLK1 are not well understood. Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes, and this in turn regulates mitotic spindle orientation by nucleating the growth of astral microtubules from the centrosomes. Interestingly, LRRK1 in turn phosphorylates CDK5RAP2(Cep215), a human homologue of Drosophila Centrosomin (Cnn), in its γ-tubulin-binding motif, thus promoting the interaction of CDK5RAP2 with γ-tubulin. LRRK1 phosphorylation of CDK5RAP2 Ser 140 is necessary for CDK5RAP2-dependent microtubule nucleation. Thus, our findings provide evidence that LRRK1 regulates mitotic spindle orientation downstream of PLK1 through CDK5RAP2-dependent centrosome maturation. PMID:26192437

  8. Experimental Study on the Dynamic Performance of a New High-Speed Spindle Supported by Water-Lubricated Hybrid Bearings

    Lin Wang


    Full Text Available The dynamic performance of a new high-speed spindle supported by water-lubricated hybrid bearings is experimentally studied on a test rig. The present design allows the speed of the spindle up to 30,000 rpm, with a bearing internal diameter of 40 mm, which makes it possible to simulate many actual machining processes. Some experiments have been presented to study the mechanical and thermal behaviors of the spindle and its supporting hybrid bearings. The maximum temperature rise is less than 15°C with a speed of 30,000 rpm and a water supply pressure of 2.5 MPa. The spindle radial run-out of the rotational frequency is about 1 µm. Stability of the spindle system has been improved. The experimental results indicate that water-lubricated hybrid bearings are valuable choices to replace ceramic bearings and air bearings as support for spindles under high-speed, high-precision, and heavy-load machining conditions.

  9. Spindle-like activity appearing during paradoxical sleep in rats with iron-induced cortical focus.



    Full Text Available Under barbiturate anesthesia, male Wistar rats weighing 250-300 g were injected with 2.5 microliters of 0.2 M FeCl3 solution into the left sensori-motor cortex to induce an epileptic focus with minimal abnormal activities. Polygraphy started 1 week after the surgery, showed a spindle-like hypersynchronous activity that appeared not only in the slow wave sleep period but also during paradoxical sleep (PS. This activity had a frequency of 8-14 Hz. The amplitude was more than 200 mu v in the right (non-injected side cortex but very small in the left cortex (injected side. Isolated spike discharges were observed in an ECoG of slow wave sleep. Apart from this activity there was nothing resembling the usual sleep spindles.

  10. Time-frequency dynamics during sleep spindles on the EEG in rodents with a genetic predisposition to absence epilepsy (WAG/Rij rats)

    Hramov, Alexander E.; Sitnikova, Evgenija Y.; Pavlov, Alexey N.; Grubov, Vadim V.; Koronovskii, Alexey A.; Khramova, Marina V.


    Sleep spindles are known to appear spontaneously in the thalamocortical neuronal network of the brain during slow-wave sleep; pathological processes in the thalamocortical network may be the reason of the absence epilepsy. The aim of the present work is to study developed changes in the time-frequency structure of sleep spindles during the progressive development of the absence epilepsy in WAG/Rij rats. EEG recordings were made at age 7 and 9 months. Automatic recognition and subsequent analysis of sleep spindles on the EEG were performed using the continuous wavelet transform. The duration of epileptic discharges and the total duration of epileptic activity were found to increase with age, while the duration of sleep spindles, conversely, decreased. In terms of the mean frequency, sleep spindles could be divided into three classes: `slow' (mean frequency 9.3Hz), `medium' (11.4Hz), and `fast' (13.5Hz). Slow and medium (transitional) spindles in five-month-old animals showed increased frequency from the beginning to the end of the spindle. The more intense the epilepsy is, the shorter are the durations of spindles of all types. The mean frequencies of `medium' and `fast' spindles were higher in rats with more intense signs of epilepsy. Overall, high epileptic activity in WAG/Rij rats was linked with significant changes in spindles of the transitional type, with less marked changes in the two traditionally identified types of spindle, slow and fast.

  11. Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.

    Zhong Rong Zhang

    Full Text Available Andrographolide (Andro suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC, alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.

  12. Mitotic spindle perturbations

    Tame, M.A.


    Microtubules are major components of the cytoskeleton and form the bipolar spindle apparatus during mitosis. The mitotic spindle consists of highly dynamic microtubule polymers that are under constant modulation, controlled by multiple motor proteins and microtubule-associated proteins. This tight s

  13. Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC–spindle interaction to ensure proper microtubule dynamics

    Nakajima, Yuko; Cormier, Anthony; Tyers, Randall G.; Pigula, Adrianne; Peng, Yutian; Drubin, David G; Barnes, Georjana


    Dynamic microtubules facilitate chromosome arrangement before anaphase, whereas during anaphase microtubule stability assists chromosome separation. Changes in microtubule dynamics at the metaphase–anaphase transition are regulated by Cdk1. Cdk1-mediated phosphorylation of Sli15/INCENP promotes preanaphase microtubule dynamics by preventing chromosomal passenger complex (CPC; Sli15/INCENP, Bir1/Survivin, Nbl1/Borealin, Ipl1/Aurora) association with spindles. However, whether Cdk1 has sole con...

  14. csi2p modulates microtubule dynamics and organizes the bipolar spindle for chromosome segregation

    Costa, Judite; Fu, Chuanhai; Khare, V. Mohini; Tran, Phong T.


    Proper chromosome segregation is of paramount importance for proper genetic inheritance. Defects in chromosome segregation can lead to aneuploidy, which is a hallmark of cancer cells. Eukaryotic chromosome segregation is accomplished by the bipolar spindle. Additional mechanisms, such as the spindle assembly checkpoint and centromere positioning, further help to ensure complete segregation fidelity. Here we present the fission yeast csi2 +. csi2p localizes to the spindle poles, where it regul...

  15. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer

    Purcell, James W; Davis, Jefferson; Reddy, Mamatha; Martin, Shamra; Samayoa, Kimberly; Vo, Hung; Thomsen, Karen; Bean, Peter; Kuo, Wen Lin; Ziyad, Safiyyah; Billig, Jessica; Feiler, Heidi S; Gray, Joe W; Wood, Kenneth W; Cases, Sylvaine


    Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein (KSP), a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have demonstrated a 9% response rate in patients with locally advanced or metastatic breast cancer, and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer we explored the activity of ispinesib alone and in combination several therapies approved for the treatment of breast cancer. We measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo, and tested the ability of ispinesib to enhance the anti-tumor activity of approved therapies. In vitro, ispinesib displayed broad anti-proliferative activity against a panel of 53 breast cell-lines. In vivo, ispinesib produced regressions in each of five breast cancer models, and tumor free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the anti-tumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine, and exhibited activity comparable to paclitaxel and ixabepilone. These findings support further clinical exploration of KSP inhibitors for the treatment of breast cancer.

  16. A novel role for the GTPase-activating protein Bud2 in the spindle position checkpoint.

    Scott A Nelson

    Full Text Available The spindle position checkpoint (SPC ensures correct mitotic spindle position before allowing mitotic exit in the budding yeast Saccharomyces cerevisiae. In a candidate screen for checkpoint genes, we identified bud2Δ as deficient for the SPC. Bud2 is a GTPase activating protein (GAP, and the only known substrate of Bud2 was Rsr1/Bud1, a Ras-like GTPase and a central component of the bud-site-selection pathway. Mutants lacking Rsr1/Bud1 had no checkpoint defect, as did strains lacking and overexpressing Bud5, a guanine-nucleotide exchange factor (GEF for Rsr1/Bud1. Thus, the checkpoint function of Bud2 is distinct from its role in bud site selection. The catalytic activity of the Bud2 GAP domain was required for the checkpoint, based on the failure of the known catalytic point mutant Bud2(R682A to function in the checkpoint. Based on assays of heterozygous diploids, bud2(R682A, was dominant for loss of checkpoint but recessive for bud-site-selection failure, further indicating a separation of function. Tem1 is a Ras-like protein and is the critical regulator of mitotic exit, sitting atop the mitotic exit network (MEN. Tem1 is a likely target for Bud2, supported by genetic analyses that exclude other Ras-like proteins.

  17. Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis.

    Wandke, Cornelia; Barisic, Marin; Sigl, Reinhard; Rauch, Veronika; Wolf, Frank; Amaro, Ana C; Tan, Chia H; Pereira, Antonio J; Kutay, Ulrike; Maiato, Helder; Meraldi, Patrick; Geley, Stephan


    Chromokinesins are microtubule plus end-directed motor proteins that bind to chromosome arms. In Xenopus egg cell-free extracts, Xkid and Xklp1 are essential for bipolar spindle formation but the functions of the human homologues, hKID (KIF22) and KIF4A, are poorly understood. By using RNAi-mediated protein knockdown in human cells, we find that only co-depletion delayed progression through mitosis in a Mad2-dependent manner. Depletion of hKID caused abnormal chromosome arm orientation, delayed chromosome congression, and sensitized cells to nocodazole. Knockdown of KIF4A increased the number and length of microtubules, altered kinetochore oscillations, and decreased kinetochore microtubule flux. These changes were associated with failures in establishing a tight metaphase plate and an increase in anaphase lagging chromosomes. Co-depletion of both chromokinesins aggravated chromosome attachment failures, which led to mitotic arrest. Thus, hKID and KIF4A contribute independently to the rapid and correct attachment of chromosomes by controlling the positioning of chromosome arms and the dynamics of microtubules, respectively. PMID:22945934

  18. Using Photobleaching to Measure Spindle Microtubule Dynamics in Primary Cultures of Dividing Drosophila Meiotic Spermatocytes

    Savoian, Matthew S.


    In dividing animal cells, a microtubule (MT)-based bipolar spindle governs chromosome movement. Current models propose that the spindle facilitates and/or generates translocating forces by regionally depolymerizing the kinetochore fibers (k-fibers) that bind each chromosome. It is unclear how conserved these sites and the resultant chromosome-moving mechanisms are between different dividing cell types because of the technical challenges of quantitatively studying MTs in many specimens. In par...

  19. Self-organization mechanisms in the assembly and maintenance of bipolar spindles

    Burbank, Kendra Stewart

    Anastral, meiotic spindles are thought to be organized differently from astral, mitotic spindles, but the field has lacked basic structural information required to describe and model them, including the location of microtubule nucleating sites and minus ends. How the various components of spindles act together to establish and maintain the dynamic bipolar structure of spindles is not understood. We measure the distributions of oriented microtubules (MTs) in metaphase anastral spindles in Xenopus extracts by fluorescence speckle microscopy and cross-correlation analysis. We localized plus ends by tubulin incorporation and combined this with the orientation data to infer the localization of minus ends. We find that minus ends are localized throughout the spindle, sparsely at the equator and at higher concentrations near the poles. This dads to the surprising conclusion that spindles contained many short MTs, not connected to the spindle poles. Based on these data, we propose a slide-and-cluster model based on four known molecular activities: MT nucleation near chromosomes, the sliding of MTs by a plus-enddirected motor, the clustering of their minus ends by a minus-end-directed motor, and the loss of MTs by dynamic instability. This work demonstrates how the interplay between two types of motors together with continual nucleation of MTs by chromosomes could organize the MTs into spindles. Our model applies to overlapping, nonkinetochore MTs in anastral spindles, and perhaps also to interpolar MTs in astral spindles. We show mathematically that the slide-and-cluster mechanism robustly forms bipolar spindles a stable steady-state length, sometimes with sharp poles. This model accounts for several experimental observations that were difficult to explain with existing models, and is the first self contained model for anastral spindle assembly, MT sliding (known as poleward flux), and spindle bistability. Our experimental results support the slide-and-cluster scenario

  20. Dynamic Localization of the Human Papillomavirus Type 11 Origin Binding Protein E2 through Mitosis While in Association with the Spindle Apparatus

    Dao, Luan D.; Duffy, Aaron; Van Tine, Brian A.; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Broker, Thomas R.; Chow, Louise T.


    Papillomaviral DNA replicates as extrachromosomal plasmids in squamous epithelium. Viral DNA must segregate equitably into daughter cells to persist in dividing basal/parabasal cells. We have previously reported that the viral origin binding protein E2 of human papillomavirus types 11 (HPV-11), 16, and 18 colocalized with the mitotic spindles. In this study, we show the localization of the HPV-11 E2 protein to be dynamic. It colocalized with the mitotic spindles during prophase and metaphase....

  1. Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

    Elena eCid


    Full Text Available Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e. the multiple-hit hypothesis. However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1; including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

  2. Spectrotemporal receptive fields during spindling and non-spindling epochs in cat primary auditory cortex.

    Britvina, T; Eggermont, J J


    It was often thought that synchronized rhythmic epochs of spindle waves disconnect thalamo-cortical system from incoming sensory signals. The present study addresses this issue by simultaneous extracellular action potential and local field potential (LFP) recordings from primary auditory cortex of ketamine-anesthetized cats during spindling activity. We compared cortical spectrotemporal receptive fields (STRF) obtained during spindling and non-spindling epochs. The basic spectro-temporal parameters of "spindling" and "non-spindling" STRFs were similar. However, the peak-firing rate at the best frequency was significantly enhanced during spindling epochs. This enhancement was mainly caused by the increased probability of a stimulus to evoke spikes (effectiveness of stimuli) during spindling as compared with non-spindling epochs. Augmented LFPs associated with effective stimuli and increased single-unit pair correlations during spindling epochs suggested higher synchrony of thalamo-cortical inputs during spindling that resulted in increased effectiveness of stimuli presented during spindling activity. The neuronal firing rate, both stimulus-driven and spontaneous, was higher during spindling as compared with non-spindling epochs. Overall, our results suggests that thalamic cells during spindling respond to incoming stimuli-related inputs and, moreover, cause more powerful stimulus-related or spontaneous activation of the cortex. PMID:18515012

  3. Spindle checkpoint activation at meiosis I advances anaphase II onset via meiosis-specific APC/C regulation

    Yamamoto, Ayumu; Kitamura, Kenji; Hihara, Daisuke; Hirose, Yukinobu; Katsuyama, Satoshi; Hiraoka, Yasushi


    During mitosis, the spindle assembly checkpoint (SAC) inhibits the Cdc20-activated anaphase-promoting complex/cyclosome (APC/CCdc20), which promotes protein degradation, and delays anaphase onset to ensure accurate chromosome segregation. However, the SAC function in meiotic anaphase regulation is poorly understood. Here, we examined the SAC function in fission yeast meiosis. As in mitosis, a SAC factor, Mad2, delayed anaphase onset via Slp1 (fission yeast Cdc20) when chromosomes attach to th...


    Zhu Yongjin; Fan Xiaoli; Wu Sudi; Li Qiang


    Objective To study the morphological changes of soleus muscle spindle and electrical activity of neurons in Red Nucleus(RN) of the rat after 2 weeks' simulated weightlessness, and to reveal the interaction between proprioceptive inputs of muscle spindles and reciprocal alterations in RN under simulated weightlessness. Methods Twenty female rats were exposed to weightlessness simulated by tail-suspension for 14 days (SW-14d). Body weight(200-220g) matched female rats were control group(Con). The morphological changes in isolated muscle spindle of soleus muscle, the discharges of red nucleus neurons were observed after 14d tail-suspensions by silver staining and extracellular recording respectively. Results Compared with control group ,the nerve ending of muscle spindle in SW-14d was distorted, degenerated and dissolved; the diameters of intrafusal fibers and capsule in equatorial region of soleus muscle spindles were diminished(P<0.05). The spontaneous cell activity and discharge of RN neurons (spikes/s) induced by afferent firing from muscle spindles after injection of succinylcholine were reduced after 2 weeks' simulated weightlessness respectively (18.44±5.96 vs. 10.19±6.88, 32.50±8.08 vs. 16.86±5.97, P<0.01). Conclusion The degeneration of muscle spindle induced by simulated weightlessness may be one of the causes that led to alterations in discharges of RN.

  5. Constitutive Cdk2 activity promotes aneuploidy while altering the spindle assembly and tetraploidy checkpoints

    Jahn, Stephan C; Corsino, Patrick E; Davis, Bradley J;


    The cell has many mechanisms for protecting the integrity of its genome. These mechanisms are often weakened or absent in many cancers, leading to high rates of chromosomal instability in tumors. Control of the cell cycle is crucial for the function of these checkpoints, and is frequently lost in...... instability. Expression of these complexes in the MCF10A cell line leads to retinoblastoma protein (Rb) hyperphosphorylation, a subsequent increase in proliferation rate, and increased expression of the spindle assembly checkpoint protein Mad2. This results in a strengthening of the spindle assembly...

  6. Location specific sleep spindle activity in the early visual areas and perceptual learning

    Bang, Ji Won; Khalilzadeh, Omid; Hämäläinen, Matti; Watanabe, Takeo; Sasaki, Yuka


    Visual perceptual learning (VPL) is consolidated during sleep. However, the underlying neuronal mechanisms of consolidation are not yet fully understood. It has been suggested that the spontaneous brain oscillations that characterize sleep stages are indicative of the consolidation of learning and memory. We investigated whether sleep spindles and/or slow-waves are associated with consolidation of VPL during non-rapid eye movement (NREM) sleep during the first sleep cycle, using magnetoenceph...

  7. Spindle Bursts in Neonatal Rat Cerebral Cortex.

    Yang, Jenq-Wei; Reyes-Puerta, Vicente; Kilb, Werner; Luhmann, Heiko J


    Spontaneous and sensory evoked spindle bursts represent a functional hallmark of the developing cerebral cortex in vitro and in vivo. They have been observed in various neocortical areas of numerous species, including newborn rodents and preterm human infants. Spindle bursts are generated in complex neocortical-subcortical circuits involving in many cases the participation of motor brain regions. Together with early gamma oscillations, spindle bursts synchronize the activity of a local neuronal network organized in a cortical column. Disturbances in spindle burst activity during corticogenesis may contribute to disorders in cortical architecture and in the activity-dependent control of programmed cell death. In this review we discuss (i) the functional properties of spindle bursts, (ii) the mechanisms underlying their generation, (iii) the synchronous patterns and cortical networks associated with spindle bursts, and (iv) the physiological and pathophysiological role of spindle bursts during early cortical development. PMID:27034844

  8. The Case of the Disappearing Spindle Burst

    Alexandre Tiriac


    Full Text Available Sleep spindles are brief cortical oscillations at 10–15 Hz that occur predominantly during non-REM (quiet sleep in adult mammals and are thought to contribute to learning and memory. Spindle bursts are phenomenologically similar to sleep spindles, but they occur predominantly in early infancy and are triggered by peripheral sensory activity (e.g., by retinal waves; accordingly, spindle bursts are thought to organize neural networks in the developing brain and establish functional links with the sensory periphery. Whereas the spontaneous retinal waves that trigger spindle bursts in visual cortex are a transient feature of early development, the myoclonic twitches that drive spindle bursts in sensorimotor cortex persist into adulthood. Moreover, twitches—and their associated spindle bursts—occur exclusively during REM (active sleep. Curiously, despite the persistence of twitching into adulthood, twitch-related spindle bursts have not been reported in adult sensorimotor cortex. This raises the question of whether such spindle burst activity does not occur in adulthood or, alternatively, occurs but has yet to be discovered. If twitch-related spindle bursts do occur in adults, they could contribute to the calibration, maintenance, and repair of sensorimotor systems.

  9. The Case of the Disappearing Spindle Burst.

    Tiriac, Alexandre; Blumberg, Mark S


    Sleep spindles are brief cortical oscillations at 10-15 Hz that occur predominantly during non-REM (quiet) sleep in adult mammals and are thought to contribute to learning and memory. Spindle bursts are phenomenologically similar to sleep spindles, but they occur predominantly in early infancy and are triggered by peripheral sensory activity (e.g., by retinal waves); accordingly, spindle bursts are thought to organize neural networks in the developing brain and establish functional links with the sensory periphery. Whereas the spontaneous retinal waves that trigger spindle bursts in visual cortex are a transient feature of early development, the myoclonic twitches that drive spindle bursts in sensorimotor cortex persist into adulthood. Moreover, twitches-and their associated spindle bursts-occur exclusively during REM (active) sleep. Curiously, despite the persistence of twitching into adulthood, twitch-related spindle bursts have not been reported in adult sensorimotor cortex. This raises the question of whether such spindle burst activity does not occur in adulthood or, alternatively, occurs but has yet to be discovered. If twitch-related spindle bursts do occur in adults, they could contribute to the calibration, maintenance, and repair of sensorimotor systems. PMID:27119028

  10. A Minus-End–directed Kinesin with Plus-End Tracking Protein Activity Is Involved in Spindle MorphogenesisV⃞

    Ambrose, J. Christian; Li, Wuxing; Marcus, Adam; Ma, Hong; Cyr, Richard


    Diverse kinesin motor proteins are involved in spindle function; however, the mechanisms by which they are targeted to specific sites within spindles are not well understood. Here, we show that a fusion between yellow fluorescent protein (YFP) and a minus-end–directed Kinesin-14 (C-terminal family) from Arabidopsis, ATK5, localizes to mitotic spindle midzones and regions rich in growing plus-ends within phragmoplasts. Notably, in Arabidopsis interphase cells, YFP::ATK5 localizes to microtubul...

  11. Visualizing the spindle checkpoint in Drosophila spermatocytes

    Rebollo, Elena; González, Cayetano


    The spindle assembly checkpoint detects defects in spindle structure or in the alignment of the chromosomes on the metaphase plate and delays the onset of anaphase until defects are corrected. Thus far, the evidence regarding the presence of a spindle checkpoint during meiosis in male Drosophila has been indirect and contradictory. On the one hand, chromosomes without pairing partners do not prevent meiosis progression. On the other hand, some conserved components of the spindle checkpoint machinery are expressed in these cells and behave as their homologue proteins do in systems with an active spindle checkpoint. To establish whether the spindle checkpoint is active in Drosophila spermatocytes we have followed meiosis progression by time-lapse microscopy under conditions where the checkpoint is likely to be activated. We have found that the presence of a relatively high number of misaligned chromosomes or a severe disruption of the meiotic spindle results in a significant delay in the time of entry into anaphase. These observations provide the first direct evidence substantiating the activity of a meiotic spindle checkpoint in male Drosophila. PMID:11256627

  12. 主轴系统动态误差和热漂移误差的测试分析%Spindle System Dynamic Error and Hot Drift Error Test Analysis

    王莹; 谢禹钧; 姚子生


    The dynamic error and hot drift error directly influence the accuracy of machine tool and workpiece surface processing quality. The dynamic error and API spindle thermal deformation analyzer and error analysis software API spindle vertical machining center of spindle for dynamic error and hot drift test. Measurement system can be harvested the temperature change of the spindle system and distribution data and main shaft system thermal deformation data, understand and master the machine tool during the work and the actual working condition of the spindle system, such as thermal equilibrium time, spindle system in all directions at different deformation and other information, of spindle system optimization design and dynamic compensation provide basic data for the support.%主轴的动态误差和热漂移误差直接影响机床的定位精度和工件表面加工质量.运用API主轴动态误差及热变形分析仪和API主轴误差分析软件对加工中心的主轴进行动态误差和热漂移测试.通过测量系统采集到的机床主轴系统的温度变化及分布数据及主轴系统的热变形数据,可以了解及掌握机床在运转过程中主轴系统的实际工况,如热平衡时间、主轴系统不同时刻在各方向的变形量等信息,对以后主轴系统的优化设计和动态补偿提供了基础数据支撑.

  13. Optogenetically induced sleep spindle rhythms alter sleep architectures in mice

    Kim, Angela; Latchoumane, Charles; Lee, Soojung; Kim, Guk Bae; Cheong, Eunji; Augustine, George J.; Shin, Hee-Sup


    Sleep spindles are rhythmic patterns of neuronal activity generated within the thalamocortical circuit. Although spindles have been hypothesized to protect sleep by reducing the influence of external stimuli, it remains to be confirmed experimentally whether there is a direct relationship between sleep spindles and the stability of sleep. We have addressed this issue by using in vivo photostimulation of the thalamic reticular nucleus of mice to generate spindle oscillations that are structura...



    Objective To investigate the role of NRM in the antinociceptive effect of muscle spindle afferents, the influence of NRM lesion on the inhibitory effect of muscle spindle afferents on the nociceptive responses of wide dynamic range (WDR) neurons and the effects of the muscle spindle afferents on the NRM neuronal activities were observed. Methods The single units of WDR neurons in the spinal dorsal horn were recorded extracellularly, and the inhibitory effects of activating muscle spindle afferents by intravenous administration of succinyicholine (SCH) on the C-fibers evoked responses (C-responses) of WDR neurons were tested before and after lesion of NRM. The ef- fects of the muscle spindle afferents activated by administrating SCH on the single NRM neurons were also examined. Results ①lt was found that the C-responses of WDR neurons were significantly inhibited by intravenously adminis- tration of SCH, and the inhibitory effect was reduced after lesion of NRM ;②The activities of most of the NRM neu- rons could be changed significantly by administrating SCH. According to their responses, NRM neurons could be classified into three types:excitatory, inhibitory and non-responsive neurons, and the responses were dose-depen- dent. Conclusion These results suggest that the muscle spindle afferents evoked by SCH may activate the NRM neu- rons, which plays an important role in the antinociception of muscle spindle afferents.

  15. Optimal Control and H∞ Output Feedback Design Options for Active Magnetic Bearing Spindle Position Regulation

    Yifei Yang


    Full Text Available For the demand of high speed and high accuracy, the use of active magnetic bearing (AMB plays a key role in various industries such as clean rooms, compressors and satellites due to their contactless nature. In this research, two other control options for high speed machine were designed based on the optimal output feedback and H∞ output feedback control methods to improve the radical and axial position regulation of AMB. The output feedback control gain matrix with the minimum performance index is obtained by solving the Riccati equation and fed back to the system in order to achieve the system’s performance. The above designed controllers can efficiently regulate the radial and axial directions position deviation of for AMB systems. Simulations for the two control methods were carried out using Matlab and Simulink for AMB system models. Results show that the H∞ output feedback controller has a better position deviation control performance over the optimal output feedback under condition of decreasing the disturbance of reaction. Finally, simulations results demonstrate that the H∞ Output Feedback is effective.

  16. Pins homolog LGN regulates meiotic spindle organization in mouse oocytes

    Xinzheng Guo; Shaorong Gao


    Mouse oocytes undergo polarization during meiotic maturation, and this polarization is essential for asymmetric cell divisions that maximize retention of maternal components required for early development. Without conventional centrosomes, the meiotic spindle has less focused poles and is barrel-shaped. The migration of meiotic spindles to the cortex is accompanied by a local reorganization and polarization of the cortex. LGN is a conserved protein involved in cell polarity and regulation of spindle organization. In the present study, we characterized the localization dynam-ics of LGN during mouse oocyte maturation and analyzed the effects of LGN upregulation and downregulation on meiotic spindle organization. At the germinal vesicle stage, LGN is distributed both cytoplasmically and at the cor-tex. During maturation, LGN localizes to the meiotic spindle apparatus and cortical LGN becomes less concentrated at the actin cap region. Excessive LGN induces meiotic spindle organization defects by elongating the spindle and enhancing pole focusing, whereas depletion of LGN by RNA interference results in meiotic spindle deformation and chromosome misalignment. Furthermore, the N-terminus of LGN has the ability of full-length LGN to regulate spin-dle organization, whereas the C-terminus of LGN controls cortical localization and polarization. Our results reveal that LGN is cortically polarized in mouse oocytes and is critical for meiotic spindle organization.

  17. Chromosome misalignments induce spindle-positioning defects.

    Tame, Mihoko A; Raaijmakers, Jonne A; Afanasyev, Pavel; Medema, René H


    Cortical pulling forces on astral microtubules are essential to position the spindle. These forces are generated by cortical dynein, a minus-end directed motor. Previously, another dynein regulator termed Spindly was proposed to regulate dynein-dependent spindle positioning. However, the mechanism of how Spindly regulates spindle positioning has remained elusive. Here, we find that the misalignment of chromosomes caused by Spindly depletion is directly provoking spindle misorientation. Chromosome misalignments induced by CLIP-170 or CENP-E depletion or by noscapine treatment are similarly accompanied by severe spindle-positioning defects. We find that cortical LGN is actively displaced from the cortex when misaligned chromosomes are in close proximity. Preventing the KT recruitment of Plk1 by the depletion of PBIP1 rescues cortical LGN enrichment near misaligned chromosomes and re-establishes proper spindle orientation. Hence, KT-enriched Plk1 is responsible for the negative regulation of cortical LGN localization. In summary, we uncovered a compelling molecular link between chromosome alignment and spindle orientation defects, both of which are implicated in tumorigenesis. PMID:26882550

  18. A cell cycle timer for asymmetric spindle positioning.

    Erin K McCarthy Campbell


    Full Text Available The displacement of the mitotic spindle to one side of a cell is important for many cells to divide unequally. While recent progress has begun to unveil some of the molecular mechanisms of mitotic spindle displacement, far less is known about how spindle displacement is precisely timed. A conserved mitotic progression mechanism is known to time events in dividing cells, although this has never been linked to spindle displacement. This mechanism involves the anaphase-promoting complex (APC, its activator Cdc20/Fizzy, its degradation target cyclin, and cyclin-dependent kinase (CDK. Here we show that these components comprise a previously unrecognized timer for spindle displacement. In the Caenorhabditis elegans zygote, mitotic spindle displacement begins at a precise time, soon after chromosomes congress to the metaphase plate. We found that reducing the function of the proteasome, the APC, or Cdc20/Fizzy delayed spindle displacement. Conversely, inactivating CDK in prometaphase caused the spindle to displace early. The consequence of experimentally unlinking spindle displacement from this timing mechanism was the premature displacement of incompletely assembled components of the mitotic spindle. We conclude that in this system, asymmetric positioning of the mitotic spindle is normally delayed for a short time until the APC inactivates CDK, and that this delay ensures that the spindle does not begin to move until it is fully assembled. To our knowledge, this is the first demonstration that mitotic progression times spindle displacement in the asymmetric division of an animal cell. We speculate that this link between the cell cycle and asymmetric cell division might be evolutionarily conserved, because the mitotic spindle is displaced at a similar stage of mitosis during asymmetric cell divisions in diverse systems.

  19. Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis

    Moore Finola E


    Full Text Available Abstract The execution of the mitotic program with high fidelity is dependent upon precise spatiotemporal regulation of posttranslational protein modifications. For example, the timely polyubiquitination of critical mitotic regulators by Anaphase Promoting Complex/Cyclosome (APC/C is essential for the metaphase to anaphase transition and mitotic exit. The spindle assembly checkpoint prevents unscheduled activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of kinetochores to mitotic spindle and facilitating equal segregation of sister chromatids. The critical effector of the spindle checkpoint, Mitotic arrest deficient 2 (Mad2, is recruited to unattached kinetochores forming a complex with other regulatory proteins to efficiently and cooperatively inhibit APC/C-Cdc20. A weakened and/or dysfunctional spindle checkpoint has been linked to the development of genomic instability in both cell culture and animal models, and evidence suggests that aberrant regulation of the spindle checkpoint plays a critical role in human carcinogenesis. Recent studies have illuminated a network of both degradative and non-degradative ubiquitination events that regulate the metaphase to anaphase transition and mitotic exit. Within this context, our recent work showed that the HECT (Homologous to E6-AP C-terminus-family E3 ligase Smurf2 (Smad specific ubiquitin regulatory factor 2, known as a negative regulator of transforming growth factor-beta (TGF-β signaling, is required for a functional spindle checkpoint by promoting the functional localization and stability of Mad2. Here we discuss putative models explaining the role of Smurf2 as a new regulator in the spindle checkpoint. The dynamic mitotic localization of Smurf2 to the centrosome and other critical mitotic structures provides implications about mitotic checkpoint control dependent on various ubiquitination events. Finally, deregulated Smurf2 activity may contribute to carcinogenesis by

  20. Dynamic Performance of Planar Parallel Mechanism and Spindle Coupling System%平面并联机构与电主轴耦合系统动态性能研究

    宋方臻; 冯会民; 刘慧


    The dynamic performance of parallel machine tool is one of the main factors that affect the machining precision.Therefore, the influence of dynamic parameters on the dynamic performance of the planar parallel machine tool must be investigated from the view point of planar parallel mechanism and spindle coupling system.According to the dynamics model of planar parallel mechanism and spindle coupling system established, the influence of dynamic parameters on dynamic performance of planar parallel mechanism and spindle coupling system was studied by means of numerical method.Results show that the influence of the dynamic parameters of the planar parallel mechanism on the coupling system dynamic performance is dominant.In comparison, the influence of the dynamic parameters of motorized spindle on the coupling system dynamic performance is smaller.Therefore, in order to improve the machining precision and dynamic performance of the planar parallel machine tool, the planar parallel mechanism should be taken into account, that is, the stiffness and damping of parallel bars should be increased appropriately.%并联机床的动态性能是影响其精度的主要因素之一,因此,必须从平面并联机构与电主轴耦合系统的角度出发,研究动力学参数变化对平面并联机床动态性能的影响.根据已建立的平面并联机构与电主轴耦合系统动力学模型,运用数值方法研究了动力学参数变化对耦合系统动态性能的影响.结果表明平面并联机构的动力学参数对耦合系统动态性能的影响占主导地位.相比较而言,电主轴的动力学参数对耦合系统的动态性能影响较小.因此,在提高平面并联机床的加工精度和动态性能时,应该着重考虑平面并联机构,适当地增大并联杆件的刚度和阻尼.

  1. Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors.

    Takahito Yumoto

    Full Text Available Developmental dynamics of neural stem/progenitor cells (NSPCs are crucial for embryonic and adult neurogenesis, but its regulatory factors are not fully understood. By differential subtractive screening with NSPCs versus their differentiated progenies, we identified the radmis (radial fiber and mitotic spindle/ckap2l gene, a novel microtubule-associated protein (MAP enriched in NSPCs. Radmis is a putative substrate for the E3-ubiquitin ligase, anaphase promoting complex/cyclosome (APC/C, and is degraded via the KEN box. Radmis was highly expressed in regions of active neurogenesis throughout life, and its distribution was dynamically regulated during NSPC division. In embryonic and perinatal brains, radmis localized to bipolar mitotic spindles and radial fibers (basal processes of dividing NSPCs. As central nervous system development proceeded, radmis expression was lost in most brain regions, except for several neurogenic regions. In adult brain, radmis expression persisted in the mitotic spindles of both slowly-dividing stem cells and rapid amplifying progenitors. Overexpression of radmis in vitro induced hyper-stabilization of microtubules, severe defects in mitotic spindle formation, and mitotic arrest. In vivo gain-of-function using in utero electroporation revealed that radmis directed a reduction in NSPC proliferation and a concomitant increase in cell cycle exit, causing a reduction in the Tbr2-positive basal progenitor population and shrinkage of the embryonic subventricular zone. Besides, radmis loss-of-function by shRNAs induced the multipolar mitotic spindle structure, accompanied with the catastrophe of chromosome segregation including the long chromosome bridge between two separating daughter nuclei. These findings uncover the indispensable role of radmis in mitotic spindle formation and cell-cycle progression of NSPCs.

  2. Rab11 endosomes contribute to mitotic spindle organization and orientation.

    Hehnly, Heidi; Doxsey, Stephen


    During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 endosomes in mitosis. Here, we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind γ-TuRC components and associate with tubulin in vitro. Rab11 depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively active Rab11 increases astral microtubules, restores γ-tubulin spindle pole localization, and generates robust spindles. This suggests a role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes cocontribute to these processes through retrograde transport to poles by dynein. PMID:24561039

  3. Anastral spindle assembly and γ-tubulin in Drosophila oocytes

    Hallen Mark A


    Full Text Available Abstract Background Anastral spindles assemble by a mechanism that involves microtubule nucleation and growth from chromatin. It is still uncertain whether γ-tubulin, a microtubule nucleator essential for mitotic spindle assembly and maintenance, plays a role. Not only is the requirement for γ-tubulin to form anastral Drosophila oocyte meiosis I spindles controversial, but its presence in oocyte meiosis I spindles has not been demonstrated and is uncertain. Results We show, for the first time, using a bright GFP fusion protein and live imaging, that the Drosophila maternally-expressed γTub37C is present at low levels in oocyte meiosis I spindles. Despite this, we find that formation of bipolar meiosis I spindles does not require functional γTub37C, extending previous findings by others. Fluorescence photobleaching assays show rapid recovery of γTub37C in the meiosis I spindle, similar to the cytoplasm, indicating weak binding by γTub37C to spindles, and fits of a new, potentially more accurate model for fluorescence recovery yield kinetic parameters consistent with transient, diffusional binding. Conclusions The FRAP results, together with its mutant effects late in meiosis I, indicate that γTub37C may perform a role subsequent to metaphase I, rather than nucleating microtubules for meiosis I spindle formation. Weak binding to the meiosis I spindle could stabilize pre-existing microtubules or position γ-tubulin for function during meiosis II spindle assembly, which follows rapidly upon oocyte activation and completion of the meiosis I division.

  4. A Single-phase Spindle Motor Design for DVD Application


    A. single phase brushless spindle motor with innovative design has been deyeloped for application in a DVD drive. The methods used to reduce the cogging torque and to improve the dynamic performance of this new design motor are proposed in this paper. The single phase brushless spindle motor is usually applied for cooling fan, pump and blower before the performance is improved by the reengineering process. The stator configuration and the drive circuit have been remodeled in order to meet the requirements of the spindle motor used in the DVD applications.

  5. Sleep spindles predict stress-related increases in sleep disturbances

    Thien Thanh eDang-Vu


    Full Text Available Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. Methods: 12 healthy students had a polysomnography (PSG recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the Insomnia Severity Index (ISI. They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration and frequency, as well as sigma power were computed from C4-O2 electroencephalography (EEG derivation during stages N2-N3 of non-rapid-eye-movement (NREM sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester.Results: Spindle density (as well as spindle amplitude and sigma power, particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05. Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

  6. Tracking dynamic team activity

    Tambe, M. [Univ. of Southern California, Marina del Rey, CA (United States)


    AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesis underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.

  7. The forces that center the mitotic spindle in the C. elegans embryo

    Garzon-Coral, Carlos


    The precise positioning of the mitotic spindle to the cell center during mitosis is a fundamental process for chromosome segregation and the division plane definition. Despite its importance, the mechanism for spindle centering remains elusive. To study this mechanism, the dynamic of the microtubules was characterized at the bulk and at the cortex in the C. elegans embryo. Then, this dynamic was correlated to the centering forces of the spindle that were studied by applying calibrated magneti...

  8. Human ASPM participates in spindle organisation, spindle orientation and cytokinesis

    Woods C Geoffrey


    Full Text Available Abstract Background Mutations in the Abnormal Spindle Microcephaly related gene (ASPM are the commonest cause of autosomal recessive primary microcephaly (MCPH a disorder characterised by a small brain and associated mental retardation. ASPM encodes a mitotic spindle pole associated protein. It is suggested that the MCPH phenotype arises from proliferation defects in neural progenitor cells (NPC. Results We show that ASPM is a microtubule minus end-associated protein that is recruited in a microtubule-dependent manner to the pericentriolar matrix (PCM at the spindle poles during mitosis. ASPM siRNA reduces ASPM protein at the spindle poles in cultured U2OS cells and severely perturbs a number of aspects of mitosis, including the orientation of the mitotic spindle, the main determinant of developmental asymmetrical cell division. The majority of ASPM depleted mitotic cells fail to complete cytokinesis. In MCPH patient fibroblasts we show that a pathogenic ASPM splice site mutation results in the expression of a novel variant protein lacking a tripeptide motif, a minimal alteration that correlates with a dramatic decrease in ASPM spindle pole localisation. Moreover, expression of dominant-negative ASPM C-terminal fragments cause severe spindle assembly defects and cytokinesis failure in cultured cells. Conclusions These observations indicate that ASPM participates in spindle organisation, spindle positioning and cytokinesis in all dividing cells and that the extreme C-terminus of the protein is required for ASPM localisation and function. Our data supports the hypothesis that the MCPH phenotype caused by ASPM mutation is a consequence of mitotic aberrations during neurogenesis. We propose the effects of ASPM mutation are tolerated in somatic cells but have profound consequences for the symmetrical division of NPCs, due to the unusual morphology of these cells. This antagonises the early expansion of the progenitor pool that underpins cortical

  9. Regulation of mitotic spindle orientation: an integrated view.

    di Pietro, Florencia; Echard, Arnaud; Morin, Xavier


    Mitotic spindle orientation is essential for cell fate decisions, epithelial maintenance, and tissue morphogenesis. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. Early studies identified the evolutionarily conserved Gαi/LGN/NuMA complex as a key regulator that polarizes cortical force generators. In recent years, a combination of genetics, biochemistry, modeling, and live imaging has contributed to decipher the mechanisms of spindle orientation. Here, we highlight the dynamic nature of the assembly of this complex and discuss the molecular regulation of its localization. Remarkably, a number of LGN-independent mechanisms were described recently, whereas NuMA remains central in most pathways involved in recruiting force generators at the cell cortex. We also describe the emerging role of the actin cortex in spindle orientation and discuss how dynamic astral microtubule formation is involved. We further give an overview on instructive external signals that control spindle orientation in tissues. Finally, we discuss the influence of cell geometry and mechanical forces on spindle orientation. PMID:27432284

  10. Kinase signaling in the spindle checkpoint.

    Kang, Jungseog; Yu, Hongtao


    The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the "wait anaphase" signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects. PMID:19228686

  11. Sleep Spindles as an Electrographic Element: Description and Automatic Detection Methods

    Maquet, Pierre


    Sleep spindle is a peculiar oscillatory brain pattern which has been associated with a number of sleep (isolation from exteroceptive stimuli, memory consolidation) and individual characteristics (intellectual quotient). Oddly enough, the definition of a spindle is both incomplete and restrictive. In consequence, there is no consensus about how to detect spindles. Visual scoring is cumbersome and user dependent. To analyze spindle activity in a more robust way, automatic sleep spindle detection methods are essential. Various algorithms were developed, depending on individual research interest, which hampers direct comparisons and meta-analyses. In this review, sleep spindle is first defined physically and topographically. From this general description, we tentatively extract the main characteristics to be detected and analyzed. A nonexhaustive list of automatic spindle detection methods is provided along with a description of their main processing principles. Finally, we propose a technique to assess the detection methods in a robust and comparable way.

  12. Sleep Spindles as an Electrographic Element: Description and Automatic Detection Methods

    Dorothée Coppieters ’t Wallant


    Full Text Available Sleep spindle is a peculiar oscillatory brain pattern which has been associated with a number of sleep (isolation from exteroceptive stimuli, memory consolidation and individual characteristics (intellectual quotient. Oddly enough, the definition of a spindle is both incomplete and restrictive. In consequence, there is no consensus about how to detect spindles. Visual scoring is cumbersome and user dependent. To analyze spindle activity in a more robust way, automatic sleep spindle detection methods are essential. Various algorithms were developed, depending on individual research interest, which hampers direct comparisons and meta-analyses. In this review, sleep spindle is first defined physically and topographically. From this general description, we tentatively extract the main characteristics to be detected and analyzed. A nonexhaustive list of automatic spindle detection methods is provided along with a description of their main processing principles. Finally, we propose a technique to assess the detection methods in a robust and comparable way.

  13. Dynamic Response Simulation of a Rotor System with Slow-time Varying Parameters of the High-speed Winder Spindle with Unbalance Masses%筒管夹头参数慢变转子系统不平衡动态响应仿真分析

    侯曦; 张凯; 刘娜娜; 杨崇倡; 王生泽


    In this paper a time-varying dynamic system with varying masses of the high-speed winder spindle is modeled and analyzed. Three formations of the spindle with different kinds of spinning cake diameters, and the spindle with time-varying masses is simulated in the way of the unbalance harmonic excitation analysis, and simula- tion results are compared. Numerical simulation which is similar to real spindle system with unbalance masses is re- alized, features of the dynamic response of the spindle system unbalance masses are obtained. It is found that the analysis of single formation without time-varying parameters would not obtain proper response of the spindle system, it is necessary to analyze the high-speed winder spindle in a way which time-varying parameters are considered in the model.%对熔融纺丝关键设备高速卷绕机筒管夹头参数慢变转子系统进行了有限元建模及不平衡谐响应分析。利用有限元分析软件建立了筒管夹头主要零部件的有限元仿真模型;谐响应分析实现了筒管三种不同丝饼直径状态和时变筒管夹头的数值仿真,得到了筒管夹头对不平衡质量的动态响应特性。发现筒管夹头处于某一卷装直径状态的动态特性不能全面表现筒管夹头工作时的实际情况,有必要对其进行近似于实际工作状态的时变筒管夹头仿真。

  14. Signal transmission from motor axons to group Ia muscle spindle afferents: frequency responses and second-order non-linearities.

    Windhorst, U; Kokkoroyiannis, T; Laouris, Y; Meyer-Lohmann, J


    Spinal recurrent inhibition via Renshaw cells and proprioceptive feedback via skeletal muscle and muscle spindle afferents have been hypothesized to constitute a compound feedback system [Windhorst (1989) Afferent Control of Posture and Locomotion; Windhorst (1993) Robots and Biological Systems--Towards a New Bionics]. To assess their detailed functions, it is necessary to know their dynamic characteristics. Previously we have extensively described the properties of signal transmission from motor axons to Renshaw cells using random motor axon stimulation and data analysis methods based thereupon. Using the same methods, we here compare these properties, in the cat, with those between motor axons and group Ia muscle spindle afferents in terms of frequency responses and nonlinear features. The frequency responses depend on the mean rate (carrier rate) of activation of motor axons and on the strength of coupling between motor units and spindles. In general, they are those of a second-order low-pass system with a cut-off at fairly low frequencies. This contrasts with the dynamics of motor axon-Renshaw cell couplings which are those of a much broader band-pass with its peak in the range of c. 2-15 Hz [Christakos (1987) Neuroscience 23, 613-623]. The second-order non-linearities in motor unit-muscle spindle signal lines are much more diverse than those in motor axon-Renshaw cell couplings. Although the average strength of response declines with mean stimulus rate in both subsystems, there is no systematic relationship between the amount of non-linearity and the average response in the former, whilst there is in the latter. The qualitative appearance of motor unit-muscle spindle non-linearities was complicated as was the average response to motor unit twitches. Thus, whilst Renshaw cells appear to dynamically reflect motor output rather faithfully, muscle spindles seem to signal local muscle fibre length changes and their dynamics. This would be consistent with the

  15. CENP-W plays a role in maintaining bipolar spindle structure.

    Agnieszka Kaczmarczyk

    Full Text Available The CENP-W/T complex was previously reported to be required for mitosis. HeLa cells depleted of CENP-W displayed profound mitotic defects, with mitotic timing delay, disorganized prometaphases and multipolar spindles as major phenotypic consequences. In this study, we examined the process of multipolar spindle formation induced by CENP-W depletion. Depletion of CENP-W in HeLa cells labeled with histone H2B and tubulin fluorescent proteins induced rapid fragmentation of originally bipolar spindles in a high proportion of cells. CENP-W depletion was associated with depletion of Hec1 at kinetochores. The possibility of promiscuous centrosomal duplication was ruled out by immunofluorescent examination of centrioles. However, centrioles were frequently observed to be abnormally split. In addition, a large proportion of the supernumerary poles lacked centrioles, but were positively stained with different centrosomal markers. These observations suggested that perturbation in spindle force distribution caused by defective kinetochores could contribute to a mechanical mechanism for spindle pole disruption. 'Spindle free' nocodazole arrested cells did not exhibit pole fragmentation after CENP-W depletion, showing that pole fragmentation is microtubule dependent. Inhibition of centrosome separation by monastrol reduced the incidence of spindle pole fragmentation, indicating that Eg5 plays a role in spindle pole disruption. Surprisingly, CENP-W depletion rescued the monopolar spindle phenotype of monastrol treatment, with an increased frequency of bipolar spindles observed after CENP-W RNAi. We overexpressed the microtubule cross-linking protein TPX2 to create spindle poles stabilized by the microtubule cross-linking activity of TPX2. Spindle pole fragmentation was suppressed in a TPX2-dependent fashion. We propose that CENP-W, by influencing proper kinetochore assembly, particularly microtubule docking sites, can confer spindle pole resistance to traction

  16. The Significance of Sigma Neurofeedback Training on Sleep Spindles and Aspects of Declarative Memory

    Berner, I.; Schabus, M; Wienerroither, T.; Klimesch, W.


    The functional significance of sleep spindles for overnight memory consolidation and general learning aptitude as well as the effect of four 10-minute sessions of spindle frequency (11.6–16 Hz, sigma) neurofeedback-training on subsequent sleep spindle activity and overnight performance change was investigated. Before sleep, subjects were trained on a paired-associate word list task after having received either neurofeedback training (NFT) or pseudofeedback training (PFT).

  17. Expert and crowd-sourced validation of an individualized sleep spindle detection method employing complex demodulation and individualized normalization

    Stuart Fogel


    Full Text Available A spindle detection method was developed that: 1 extracts the signal of interest (i.e., spindle-related phasic changes in sigma relative to ongoing “background” sigma activity using complex demodulation, 2 accounts for variations of spindle characteristics across the night, scalp derivations and between individuals, and 3 employs a minimum number of sometimes arbitrary, user-defined parameters. Complex demodulation was used to extract instantaneous power in the spindle band. To account for intra- and inter-individual differences, the signal was z-score transformed using a 60s sliding window, per channel, over the course of the recording. Spindle events were detected with a z-score threshold corresponding to a low probability (e.g., 99th percentile. Spindle characteristics, such as amplitude, duration and oscillatory frequency, were derived for each individual spindle following detection, which permits spindles to be subsequently and flexibly categorized as slow or fast spindles from a single detection pass. Spindles were automatically detected in 15 young healthy subjects. Two experts manually identified spindles from C3 during Stage 2 sleep, from each recording; one employing conventional guidelines, and the other, identifying spindles with the aid of a sigma (11-16 Hz filtered channel. These spindles were then compared between raters and to the automated detection to identify the presence of true positives, true negatives, false positives and false negatives. This method of automated spindle detection resolves or avoids many of the limitations that complicate automated spindle detection, and performs well compared to a group of non-experts, and importantly, has good external validity with respect to the extant literature in terms of the characteristics of automatically detected spindles.

  18. Intercentrosomal angular separation during mitosis plays a crucial role for maintaining spindle stability

    Sutradhar, S.; Basu, S.; Paul, R.


    Cell division through proper spindle formation is one of the key puzzles in cell biology. In most mammalian cells, chromosomes spontaneously arrange to achieve a stable bipolar spindle during metaphase which eventually ensures proper segregation of the DNA into the daughter cells. In this paper, we present a robust three-dimensional mechanistic model to investigate the formation and maintenance of a bipolar mitotic spindle in mammalian cells under different physiological constraints. Using realistic parameters, we test spindle viability by measuring the spindle length and studying the chromosomal configuration. The model strikingly predicts a feature of the spindle instability arising from the insufficient intercentrosomal angular separation and impaired sliding of the interpolar microtubules. In addition, our model successfully reproduces chromosomal patterns observed in mammalian cells, when activity of different motor proteins is perturbed.

  19. In-silico modeling of the mitotic spindle assembly checkpoint.

    Bashar Ibrahim

    Full Text Available BACKGROUND: The Mitotic Spindle Assembly Checkpoint ((MSAC is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer. PRINCIPLE FINDINGS: We have constructed and validated for the human (MSAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the (MSAC are derived. Most of the kinetic constants are taken from literature, the remaining four unknown parameters are derived by an evolutionary optimization procedure for an objective function describing the dynamics of the APC:Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the "Dissociation" and the "Convey" model variants. The attachment of the kinetochore to microtubuli is simulated by a switching parameter silencing those reactions which are stopped by the attachment. For both, the Dissociation and the Convey variants, we compare two different scenarios concerning the microtubule attachment dependent control of the dissociation reaction. Our model is validated by simulation of ten perturbation experiments. CONCLUSION: Only in the controlled case, our models show (MSAC behaviour at meta- to anaphase transition in agreement with experimental observations. Our simulations revealed that for (MSAC activation, Cdc20 is not fully sequestered; instead APC is inhibited by MCC binding.

  20. Nap sleep spindle correlates of intelligence

    Ujma, Péter P.; Róbert Bódizs; Ferenc Gombos; Johannes Stintzing; Konrad, Boris N.; Lisa Genzel; Axel Steiger; Martin Dresler


    Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fluid intelligence scores, however more recently it has been shown that only few sleep spindle measures correlate with intelligence in females, and none in males. Sleep spindle regulation underlies a...

  1. Visualizing the spindle checkpoint in Drosophila spermatocytes

    Rebollo, Elena; González, Cayetano


    The spindle assembly checkpoint detects defects in spindle structure or in the alignment of the chromosomes on the metaphase plate and delays the onset of anaphase until defects are corrected. Thus far, the evidence regarding the presence of a spindle checkpoint during meiosis in male Drosophila has been indirect and contradictory. On the one hand, chromosomes without pairing partners do not prevent meiosis progression. On the other hand, some conserved components of the spindle checkpoint ma...

  2. The Clathrin-dependent Spindle Proteome.

    Rao, Sushma R; Flores-Rodriguez, Neftali; Page, Scott L; Wong, Chin; Robinson, Phillip J; Chircop, Megan


    The mitotic spindle is required for chromosome congression and subsequent equal segregation of sister chromatids. These processes involve a complex network of signaling molecules located at the spindle. The endocytic protein, clathrin, has a "moonlighting" role during mitosis, whereby it stabilizes the mitotic spindle. The signaling pathways that clathrin participates in to achieve mitotic spindle stability are unknown. Here, we assessed the mitotic spindle proteome and phosphoproteome in clathrin-depleted cells using quantitative MS/MS (data are available via ProteomeXchange with identifier PXD001603). We report a spindle proteome that consists of 3046 proteins and a spindle phosphoproteome consisting of 5157 phosphosites in 1641 phosphoproteins. Of these, 2908 (95.4%) proteins and 1636 (99.7%) phosphoproteins are known or predicted spindle-associated proteins. Clathrin-depletion from spindles resulted in dysregulation of 121 proteins and perturbed signaling to 47 phosphosites. The majority of these proteins increased in mitotic spindle abundance and six of these were validated by immunofluorescence microscopy. Functional pathway analysis confirmed the reported role of clathrin in mitotic spindle stabilization for chromosome alignment and highlighted possible new mechanisms of clathrin action. The data also revealed a novel second mitotic role for clathrin in bipolar spindle formation. PMID:27174698

  3. Sleep Spindle Deficit in Schizophrenia: Contextualization of Recent Findings.

    Castelnovo, Anna; D'Agostino, Armando; Casetta, Cecilia; Sarasso, Simone; Ferrarelli, Fabio


    Sleep spindles are wax and waning brain oscillations at a frequency range of 11-16 Hz, lasting 0.5-2 s, that define non-rapid eye movement sleep stage 2. Over the past few years, several independent studies pointed to a decrease of sleep spindles in schizophrenia. The aim of this review is to contextualize these findings within the growing literature on these oscillations across other neuro-psychiatric disorders. Indeed, spindles reflect the coordinated activity of thalamocortical networks, and their abnormality can be observed in a variety of conditions that disrupt local or global thalamocortical connectivity. Although the broad methodological variability across studies limits the possibility of drawing firm conclusions, impaired spindling activity has been observed in several neurodevelopmental and neurodegenerative disorders. Despite such lack of specificity, schizophrenia remains the only condition with a typical late adolescence to young adulthood onset in which impaired spindling has been consistently reported. Further research is necessary to clearly define the pathogenetic mechanisms that lead to this deficit and the validity of its widespread use as a clinical biomarker. PMID:27299655

  4. Monotonicity of the dynamical activity

    Maes, C.; Netočný, Karel; Wynants, B.


    Roč. 45, č. 45 (2012), 1-13. ISSN 1751-8113 Institutional research plan: CEZ:AV0Z10100520 Keywords : nonequilibrium steady state * Lyapunov function * dynamical activity Subject RIV: BE - Theoretical Physics Impact factor: 1.766, year: 2012

  5. The vestibular system does not modulate fusimotor drive to muscle spindles in relaxed leg muscles of subjects in a near-vertical position.

    Knellwolf, T P; Hammam, E; Macefield, V G


    It has been shown that sinusoidal galvanic vestibular stimulation (sGVS) has no effect on the firing of spontaneously active muscle spindles in either relaxed or voluntarily contracting human leg muscles. However, all previous studies have been conducted on subjects in a seated position. Given that independent vestibular control of muscle spindle firing would be more valuable during postural threat, we tested the hypothesis that this modulation would become apparent for subjects in a near-vertical position. Unitary recordings were made from 18 muscle spindle afferents via tungsten microelectrodes inserted percutaneously into the common peroneal nerve of awake human subjects laying supine on a motorized tilt table. All recorded spindle afferents were spontaneously active at rest, and each increased its firing rate during a weak static contraction. Sinusoidal bipolar binaural galvanic vestibular stimulation (±2 mA, 100 cycles) was applied to the mastoid processes at 0.8 Hz. This continuous stimulation produced a sustained illusion of "rocking in a boat" or "swinging in a hammock." The subject was then moved into a near-vertical position (75°), and the stimulation repeated. Despite robust vestibular illusions, none of the fusimotor-driven spindles exhibited phase-locked modulation of firing during sinusoidal GVS in either position. We conclude that this dynamic vestibular stimulus was insufficient to modulate the firing of fusimotor neurons in the near-vertical position. However, this does not mean that the vestibular system cannot modulate the sensitivity of muscle spindles via fusimotor neurons in free unsupported standing, when reliance on proprioceptive feedback is higher. PMID:26936989

  6. Dynamics of active actin networks

    Koehler, Simone


    Local mechanical and structural properties of a eukaryotic cell are determined by its cytoskeleton. To adapt to their environment, cells rely on constant self-organized rearrangement processes of their actin cytoskeleton. To shed light on the principles underlying these dynamic self-organization processes we investigate a minimal reconstituted active system consisting of actin filaments, crosslinking molecules and molecular motor filaments. Using quantitative fluorescence microscopy and image analysis, we show, that these minimal model systems exhibit a generic structure formation mechanism. The competition between force generation by molecular motors and the stabilization of the network by crosslinking proteins results in a highly dynamic reorganization process which is characterized by anomalous transport dynamics with a superdiffusive behavior also found in intracellular dynamics. In vitro, these dynamics are governed by chemical and physical parameters that alter the balance of motor and crosslinking proteins, such as pH. These findings can be expected to have broad implications in our understanding of cytoskeletal regulation in vivo.

  7. Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.

    Rojas, Ana M; Santamaria, Anna; Malik, Rainer; Jensen, Thomas Skøt; Körner, Roman; Morilla, Ian; de Juan, David; Krallinger, Martin; Hansen, Daniel Aaen; Hoffmann, Robert; Lees, Jonathan; Reid, Adam; Yeats, Corin; Wehner, Anja; Elowe, Sabine; Clegg, Andrew B; Brunak, Søren; Nigg, Erich A; Orengo, Christine; Valencia, Alfonso; Ranea, Juan A G


    The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called "hidden spindle hub", proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system. PMID:22427808

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

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


    reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function....... Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs....

  9. Katanin maintains meiotic metaphase chromosome alignment and spindle structure in vivo and has multiple effects on microtubules in vitro.

    McNally, Karen; Berg, Evan; Cortes, Daniel B; Hernandez, Veronica; Mains, Paul E; McNally, Francis J


    Assembly of Caenorhabditis elegans female meiotic spindles requires both MEI-1 and MEI-2 subunits of the microtubule-severing ATPase katanin. Strong loss-of-function mutants assemble apolar intersecting microtubule arrays, whereas weaker mutants assemble bipolar meiotic spindles that are longer than wild type. To determine whether katanin is also required for spindle maintenance, we monitored metaphase I spindles after a fast-acting mei-1(ts) mutant was shifted to a nonpermissive temperature. Within 4 min of temperature shift, bivalents moved off the metaphase plate, and microtubule bundles within the spindle lengthened and developed a high degree of curvature. Spindles eventually lost bipolar structure. Immunofluorescence of embryos fixed at increasing temperature indicated that MEI-1 was lost from spindle microtubules before loss of ASPM-1, indicating that MEI-1 and ASPM-1 act independently at spindle poles. We quantified the microtubule-severing activity of purified MEI-1/MEI-2 complexes corresponding to six different point mutations and found a linear relationship between microtubule disassembly rate and meiotic spindle length. Previous work showed that katanin is required for severing at points where two microtubules intersect in vivo. We show that purified MEI-1/MEI-2 complexes preferentially sever at intersections between two microtubules and directly bundle microtubules in vitro. These activities could promote parallel/antiparallel microtubule organization in meiotic spindles. PMID:24501424

  10. Spindle Oscillations in Sleep Disorders: A Systematic Review

    Oren M. Weiner


    Full Text Available Measurement of sleep microarchitecture and neural oscillations is an increasingly popular technique for quantifying EEG sleep activity. Many studies have examined sleep spindle oscillations in sleep-disordered adults; however reviews of this literature are scarce. As such, our overarching aim was to critically review experimental studies examining sleep spindle activity between adults with and without different sleep disorders. Articles were obtained using a systematic methodology with a priori criteria. Thirty-seven studies meeting final inclusion criteria were reviewed, with studies grouped across three categories: insomnia, hypersomnias, and sleep-related movement disorders (including parasomnias. Studies of patients with insomnia and sleep-disordered breathing were more abundant relative to other diagnoses. All studies were cross-sectional. Studies were largely inconsistent regarding spindle activity differences between clinical and nonclinical groups, with some reporting greater or less activity, while many others reported no group differences. Stark inconsistencies in sample characteristics (e.g., age range and diagnostic criteria and methods of analysis (e.g., spindle bandwidth selection, visual detection versus digital filtering, absolute versus relative spectral power, and NREM2 versus NREM3 suggest a need for greater use of event-based detection methods and increased research standardization. Hypotheses regarding the clinical and empirical implications of these findings, and suggestions for potential future studies, are also discussed.

  11. Next generation spindles for micromilling.

    Pathak, Jay P. (Machine Tool Research Center, University of Florida, Gainesville, FL); Payne, Scott W. T. (Machine Tool Research Center, University of Florida, Gainesville, FL); Gill, David Dennis; Ziegert, John C. (Machine Tool Research Center, University of Florida, Gainesville, FL); Jokiel, Bernhard, Jr.


    There exists a wide variety of important applications for micro- and meso-scale mechanical systems in the commercial and defense sectors, which require high-strength materials and complex geometries that cannot be produced using current MEMS fabrication technologies. Micromilling has great potential to fill this void in MEMS technology by adding the capability of free form machining of complex 3D shapes from a wide variety and combination of traditional, well-understood engineering alloys, glasses and ceramics. Inefficiencies in micromilling result from the relationships between a cutting tool's breaking strength, the applied cutting force, and the metal removal rate. Because machining times in mesofeatures scale inversely to the part size, a feature 1/10th as large will take 10 times as long to machine. Also, required chip sizes of 1 m or less are cut with tools having edge radius of 2-3 m, the cutting edge effectively has a highly negative rake angle, cutting forces are increased significantly causing chip loads to be further reduced and the machining takes even longer than predicted above. However, cutting forces do not increase with cutting speed, so faster spindles with reduced tool runout are the path to achieve efficient mesoscale milling. This research explored the development of new ultra-high speed micromilling spindles. A novel air-bearing spindle design is discussed that will run at very high speeds (450,000 rpm) and provide very minimal runout allowing the best use of micromilling cutters and reducing overall machining time drastically. Two generations of this spindle design were completed; one with an air bearing supported tool shaft and one with a novel rolling element bearing supported tool shaft. Both designs utilized friction-drive systems that relied on diameter differences between the drive wheel (operating at speeds up to 90,000 rpm) and the tool shaft to achieve high rotational tool speeds. Runout, stiffness, and machining tests were

  12. The Spindle Cell Neoplasms of the Oral Cavity

    Shamim, Thorakkal


    Spindle cell neoplasms are defined as neoplasms that consist of spindle-shaped cells in the histopathology. Spindle cell neoplasms can affect the oral cavity. In the oral cavity, the origin of the spindle cell neoplasms may be traced to epithelial, mesenchymal and odontogenic components. This article aims to review the spindle cell neoplasms of the oral cavity with emphasis on histopathology.

  13. Characterization of ring-like F-actin structure as a mechanical partner for spindle positioning in mitosis.

    Huan Lu

    Full Text Available Proper spindle positioning and orientation are essential for accurate mitosis which requires dynamic interactions between microtubule and actin filament (F-actin. Although mounting evidence demonstrates the role of F-actin in cortical cytoskeleton dynamics, it remains elusive as to the structure and function of F-actin-based networks in spindle geometry. Here we showed a ring-like F-actin structure surrounding the mitotic spindle which forms since metaphase and maintains in MG132-arrested metaphase HeLa cells. This cytoplasmic F-actin structure is relatively isotropic and less dynamic. Our computational modeling of spindle position process suggests a possible mechanism by which the ring-like F-actin structure can regulate astral microtubule dynamics and thus mitotic spindle orientation. We further demonstrated that inhibiting Plk1, Mps1 or Myosin, and disruption of microtubules or F-actin polymerization perturbs the formation of the ring-like F-actin structure and alters spindle position and symmetric division. These findings reveal a previously unrecognized but important link between mitotic spindle and ring-like F-actin network in accurate mitosis and enables the development of a method to theoretically illustrate the relationship between mitotic spindle and cytoplasmic F-actin.


    FU Huinan; CHEN Dongsheng; ZHAO Yong; LIN Binquan


    A minitype precise spindle system which can machine precisely and stably in the process of diamond lapping and polishing is designed. In such minitype spindle system, the brushless DC spindle motor is used to drive the lapping finish table, which is built with fluid dynamic bearings. Some measures have been taken to make the lapping system dynamic balance, and a servo controller which can adjust the speed of motor from 1 200 r/min to 5 400 r/min is designed. Experiments show that the spindle system is reliable and stable for diamond polishing, and the detection results by atomic force microscope(AFM) show that the surfaces of diamond edge's Ra is 6.725 nm and whole diamond average Ra is 3.25 nm.

  15. Automated high-throughput quantification of mitotic spindle positioning from DIC movies of Caenorhabditis embryos.

    David Cluet

    Full Text Available The mitotic spindle is a microtubule-based structure that elongates to accurately segregate chromosomes during anaphase. Its position within the cell also dictates the future cell cleavage plan, thereby determining daughter cell orientation within a tissue or cell fate adoption for polarized cells. Therefore, the mitotic spindle ensures at the same time proper cell division and developmental precision. Consequently, spindle dynamics is the matter of intensive research. Among the different cellular models that have been explored, the one-cell stage C. elegans embryo has been an essential and powerful system to dissect the molecular and biophysical basis of spindle elongation and positioning. Indeed, in this large and transparent cell, spindle poles (or centrosomes can be easily detected from simple DIC microscopy by human eyes. To perform quantitative and high-throughput analysis of spindle motion, we developed a computer program ACT for Automated-Centrosome-Tracking from DIC movies of C. elegans embryos. We therefore offer an alternative to the image acquisition and processing of transgenic lines expressing fluorescent spindle markers. Consequently, experiments on large sets of cells can be performed with a simple setup using inexpensive microscopes. Moreover, analysis of any mutant or wild-type backgrounds is accessible because laborious rounds of crosses with transgenic lines become unnecessary. Last, our program allows spindle detection in other nematode species, offering the same quality of DIC images but for which techniques of transgenesis are not accessible. Thus, our program also opens the way towards a quantitative evolutionary approach of spindle dynamics. Overall, our computer program is a unique macro for the image- and movie-processing platform ImageJ. It is user-friendly and freely available under an open-source licence. ACT allows batch-wise analysis of large sets of mitosis events. Within 2 minutes, a single movie is processed

  16. Synergistic role of fission yeast Alp16GCP6 and Mzt1MOZART1 in γ-tubulin complex recruitment to mitotic spindle pole bodies and spindle assembly.

    Masuda, Hirohisa; Toda, Takashi


    In fission yeast, γ-tubulin ring complex (γTuRC)-specific components Gfh1(GCP4), Mod21(GCP5), and Alp16(GCP6) are nonessential for cell growth. Of these deletion mutants, only alp16Δ shows synthetic lethality with temperature-sensitive mutants of Mzt1(MOZART1), a component of the γTuRC required for recruitment of the complex to microtubule-organizing centers. γ-Tubulin small complex levels at mitotic spindle pole bodies (SPBs, the centrosome equivalent in fungi) and microtubule levels for preanaphase spindles are significantly reduced in alp16Δ cells but not in gfh1Δ or mod21Δ cells. Furthermore, alp16Δ cells often form monopolar spindles and frequently lose a minichromosome when the spindle assembly checkpoint is inactivated. Alp16(GCP6) promotes Mzt1-dependent γTuRC recruitment to mitotic SPBs and enhances spindle microtubule assembly in a manner dependent on its expression levels. Gfh1(GCP4) and Mod21(GCP5) are not required for Alp16(GCP6)-dependent γTuRC recruitment. Mzt1 has an additional role in the activation of the γTuRC for spindle microtubule assembly. The ratio of Mzt1 to γTuRC levels for preanaphase spindles is higher than at other stages of the cell cycle. Mzt1 overproduction enhances spindle microtubule assembly without affecting γTuRC levels at mitotic SPBs. We propose that Alp16(GCP6) and Mzt1 act synergistically for efficient bipolar spindle assembly to ensure faithful chromosome segregation. PMID:27053664

  17. Feedback-Controlled Transcranial Alternating Current Stimulation Reveals a Functional Role of Sleep Spindles in Motor Memory Consolidation.

    Lustenberger, Caroline; Boyle, Michael R; Alagapan, Sankaraleengam; Mellin, Juliann M; Vaughn, Bradley V; Fröhlich, Flavio


    Transient episodes of brain oscillations are a common feature of both the waking and the sleeping brain. Sleep spindles represent a prominent example of a poorly understood transient brain oscillation that is impaired in disorders such as Alzheimer's disease and schizophrenia. However, the causal role of these bouts of thalamo-cortical oscillations remains unknown. Demonstrating a functional role of sleep spindles in cognitive processes has, so far, been hindered by the lack of a tool to target transient brain oscillations in real time. Here, we show, for the first time, selective enhancement of sleep spindles with non-invasive brain stimulation in humans. We developed a system that detects sleep spindles in real time and applies oscillatory stimulation. Our stimulation selectively enhanced spindle activity as determined by increased sigma activity after transcranial alternating current stimulation (tACS) application. This targeted modulation caused significant enhancement of motor memory consolidation that correlated with the stimulation-induced change in fast spindle activity. Strikingly, we found a similar correlation between motor memory and spindle characteristics during the sham night for the same spindle frequencies and electrode locations. Therefore, our results directly demonstrate a functional relationship between oscillatory spindle activity and cognition. PMID:27476602

  18. Mechanism of the mitotic kinesin CENP-E in tethering kinetochores to spindle microtubules

    Kim, Yumi


    The mitotic kinesin CENP-E is an essential kinetochore motor that directly contributes to the capture and stabilization of spindle microtubules by kinetochores. Although it has been well established that CENP-E is essential for metaphase chromosome alignment and reduction of CENP-E leads to high rates of whole chromosome missegregation in cells, its properties as a microtubule- dependent motor, the mechanism by which CENP-E contributes to the dynamic linkage between kinetochores and spindle m...

  19. Control of position and movement is simplified by combined muscle spindle and Golgi tendon organ feedback

    Kistemaker, D.A.; Soest, van, R.W.M.; Wong, J D; Kurtzer, I; Gribble, P.L.


    Whereas muscle spindles play a prominent role in current theories of human motor control, Golgi tendon organs (GTO) and their associated tendons are often neglected. This is surprising since there is ample evidence that both tendons and GTOs contribute importantly to neuromusculoskeletal dynamics. Using detailed musculoskeletal models, we provide evidence that simple feedback using muscle spindles alone results in very poor control of joint position and movement since muscle sp...

  20. A ligand-independent integrin β1 mechanosensory complex guides spindle orientation.

    Petridou, Nicoletta I; Skourides, Paris A


    Control of spindle orientation is a fundamental process for embryonic development, morphogenesis and tissue homeostasis, while defects are associated with tumorigenesis and other diseases. Force sensing is one of the mechanisms through which division orientation is determined. Here we show that integrin β1 plays a critical role in this process, becoming activated at the lateral regions of the cell cortex in a ligand-independent manner. This activation is force dependent and polar, correlating with the spindle capture sites. Inhibition of integrin β1 activation on the cortex and disruption of its asymmetric distribution leads to spindle misorientation, even when cell adhesion is β1 independent. Examining downstream targets reveals that a cortical mechanosensory complex forms on active β1, and regulates spindle orientation irrespective of cell context. We propose that ligand-independent integrin β1 activation is a conserved mechanism that allows cell responses to external stimuli. PMID:26952307

  1. Equilibria of idealized confined astral microtubules and coupled spindle poles.

    Ivan V Maly

    Full Text Available Positioning of the mitotic spindle through the interaction of astral microtubules with the cell boundary often determines whether the cell division will be symmetric or asymmetric. This process plays a crucial role in development. In this paper, a numerical model is presented that deals with the force exerted on the spindle by astral microtubules that are bent by virtue of their confinement within the cell boundary. It is found that depending on parameters, the symmetric position of the spindle can be stable or unstable. Asymmetric stable equilibria also exist, and two or more stable positions can exist simultaneously. The theory poses new types of questions for experimental research. Regarding the cases of symmetric spindle positioning, it is necessary to ask whether the microtubule parameters are controlled by the cell so that the bending mechanics favors symmetry. If they are not, then it is necessary to ask what forces external to the microtubule cytoskeleton counteract the bending effects sufficiently to actively establish symmetry. Conversely, regarding the cases with asymmetry, it is now necessary to investigate whether the cell controls the microtubule parameters so that the bending favors asymmetry apart from any forces that are external to the microtubule cytoskeleton.

  2. Nap sleep spindle correlates of intelligence

    Ujma, P.P.; Bodizs, R.; Gombos, F.; Stintzing, J.; Konrad, B.N.; Genzel, L.; Steiger, A.; Dresler, M.


    Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fl

  3. Retropharyngeal spindle cell/plemorphic lipoma

    Lee, Hyun Kyung; Hwang, Seung Bae; Chung, Gyung Ho; Hong, Ki Hwang; Jang, Kyu Yun [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)


    Spindle cell/pleomorphic lipoma is an uncommon benign adipose tissue tumor most frequently arising from the subcutaneous tissue of the back, shoulder, head and neck, and extremities. The deep cervical spaces are the rarely affected locations. Herein we report on the imaging findings of spindle cell/pleomorphic lipoma involving the retropharyngeal space in an elderly woman.

  4. Optimization Study of the Efficient Spindle


    In the field of yam dyeing, the most generally employed method is a type of package dyeing which uses a package of cheese stacked on a spindle made of a perforated robe. Spindles up to now, have been designed without considering the characteristics of dyeing liquid, focusing only on the geometric configuration which cause many problems such as lack of level dyeing. To improve the level dyeing and find the appropriate spindle configuration for the most effective dyeing process, this study examines the spindle flow-field in detail, using a computational method. Flow characteristics inside the spindle have been investigated with varying in porosity, porous diameter and the velocity of the flow. The results show that the total pressure of the flow through the spindle is used to overcom e body force. The characteristics of the flow from the porous spindle could also be observed. Based on the results from this study, an effective spindle configuration for level-dyeing has been proposed.

  5. Chromosome position at the spindle equator is regulated by chromokinesin and a bipolar microtubule array.

    Takagi, Jun; Itabashi, Takeshi; Suzuki, Kazuya; Ishiwata, Shin'ichi


    The chromosome alignment is mediated by polar ejection and poleward forces acting on the chromosome arm and kinetochores, respectively. Although components of the motile machinery such as chromokinesin have been characterized, their dynamics within the spindle is poorly understood. Here we show that a quantum dot (Qdot) binding up to four Xenopus chromokinesin (Xkid) molecules behaved like a nanosize chromosome arm in the meiotic spindle, which is self-organized in cytoplasmic egg extracts. Xkid-Qdots travelled long distances along microtubules by changing several tracks, resulting in their accumulation toward and distribution around the metaphase plate. The analysis indicated that the direction of motion and velocity depend on the distribution of microtubule polarity within the spindle. Thus, this mechanism is governed by chromokinesin motors, which is dependent on symmetrical microtubule orientation that may allow chromosomes to maintain their position around the spindle equator until correct microtubule-kinetochore attachment is established. PMID:24077015

  6. F-actin mechanics control spindle centring in the mouse zygote

    Chaigne, Agathe; Campillo, Clément; Voituriez, Raphaël; Gov, Nir S.; Sykes, Cécile; Verlhac, Marie-Hélène; Terret, Marie-Emilie


    Mitotic spindle position relies on interactions between astral microtubules nucleated by centrosomes and a rigid cortex. Some cells, such as mouse oocytes, do not possess centrosomes and astral microtubules. These cells rely only on actin and on a soft cortex to position their spindle off-centre and undergo asymmetric divisions. While the first mouse embryonic division also occurs in the absence of centrosomes, it is symmetric and not much is known on how the spindle is positioned at the exact cell centre. Using interdisciplinary approaches, we demonstrate that zygotic spindle positioning follows a three-step process: (1) coarse centring of pronuclei relying on the dynamics of an F-actin/Myosin-Vb meshwork; (2) fine centring of the metaphase plate depending on a high cortical tension; (3) passive maintenance at the cell centre. Altogether, we show that F-actin-dependent mechanics operate the switch between asymmetric to symmetric division required at the oocyte to embryo transition.

  7. Research Progress of Key Technology of High-Speed and High Precision Motorized Spindles

    XIONG Wan-li; MI Hai-qing; HUANG Hon-gwu


    High speed machining and high precision machining are two tendencies of the manufacturing technology worldwide. The motorized spindle is the core component of the machine tools for achieving the high speed and high precise machining, which affects the general development level of the machine tools to a great extent. Progress of the key techniques is reviewed in this paper, in which the high speed and high precision spindle bearings, the dynamical and thermal characteristics of spindles, the design technique of the high frequency motors and the drivers, the anti-electromagnetic damage technique of the motors, and the machining and assembling technique are involved. Finally, tha development tendencies of the motorized spindles are presented.

  8. Attachment issues: kinetochore transformations and spindle checkpoint silencing.

    Etemad, Banafsheh; Kops, Geert J P L


    Cell division culminates in the segregation of duplicated chromosomes in opposite directions prior to cellular fission. This process is guarded by the spindle assembly checkpoint (SAC), which prevents the anaphase of cell division until stable connections between spindle microtubules and the kinetochores of all chromosomes are established. The anaphase inhibitor is generated at unattached kinetochores and inhibitor production is prevented when microtubules are captured. Understanding the molecular changes in the kinetochore that are evoked by microtubule attachments is crucial for understanding the mechanisms of SAC signaling and silencing. Here, we highlight the most recent findings on these events, pinpoint some remaining mysteries, and argue for incorporating holistic views of kinetochore dynamics in order to understand SAC silencing. PMID:26947988

  9. Rotation of Meiotic Spindle Is Controlled by Microfilaments in Mouse Oocytes

    Da-YuanChen; Jin-SongLi; LiLian; LeiLei; Zhi-MingHan; Qing-YuanSun


    The completion of meiosis requires the spatial and temporal coordination of cytokinesis and karyokirlesis. During meiotic maturation, many events, such as formation, location, and rotation of the meiotic spindle as well as chromosomal movement,Polar body extrusion,and pronuclear migration,are dependent on regulation of the cytoskeleton system.To study functions of microfilaments in meiosis,we induced metaphase Ⅱ(MII)mouse oocytes to resume meiosis by in vitro fertilization or parthenogenetic activation,and we treated such oocytes with cytochalasin B(CB).The changes of the meiotic spindle,as visualized in preparations stained for β-tubulin and chromation,were observed by fluorescent confocal microscopy.The meiotic spindle of Mll oocytes was observed to be parallel to the plasmalemma.After meiosis had resumed,the spindle rotated to the vertical position so that the second polar body could be extruded into the perivitelline space.When meiosis resumed and oocytes were treated with 10μg/ml of CB,the spindle rotation was inhibited.Consequently,the oocyte formed an extra pronucleus instead of extruding a second polar body.These results indicate that spindle rotation is essential for polar body extrusion;it is the microfilaments that play a crucial role in regulating rotation of the meiotic spindle.

  10. Automatic sleep spindle detection: Benchmarking with fine temporal resolution using open science tools

    Christian O'Reilly


    Full Text Available Sleep spindle properties index cognitive faculties such as memory consolidation and diseases such as major depression. For this reason, scoring sleep spindle properties in polysomnographic recordings has become an important activity in both research and clinical settings. The tediousness of this manual task has motivated efforts for its automation. Although some progress has been made, increasing the temporal accuracy of spindle scoring and improving the performance assessment methodology are two aspects needing more attention. In this paper, four open-access automated spindle detectors with fine temporal resolution are proposed and tested against expert scoring of two proprietary and two open-access databases. Results highlight several findings: 1 that expert scoring and polysomnographic databases are important confounders when comparing the performance of spindle detectors tested using different databases or scorings; 2 because spindles are sparse events, specificity estimates are potentially misleading for assessing automated detector performance; 3 reporting the performance of spindle detectors exclusively with sensitivity and specificity estimates, as is often seen in the literature, is insufficient; including sensitivity, precision and a more comprehensive statistic such as Matthew’s correlation coefficient, F1-score, or Cohen’s κ is necessary for adequate evaluation; 4 reporting statistics for some reasonable range of decision thresholds provides a much more complete and useful benchmarking; 5 performance differences between tested automated detectors were found to be similar to those between available expert scorings; 6 much more development is needed to effectively compare the performance of spindle detectors developed by different research teams. Finally, this work clarifies a long-standing but only seldom posed question regarding whether expert scoring truly is a reliable gold standard for sleep spindle assessment.

  11. A curved edge diffraction-utilized displacement sensor for spindle metrology

    Lee, ChaBum; Mahajan, Satish M.; Zhao, Rui; Jeon, Seongkyul


    This paper presents a new dimensional metrological sensing principle for a curved surface based on curved edge diffraction. Spindle error measurement technology utilizes a cylindrical or spherical target artifact attached to the spindle with non-contact sensors, typically a capacitive sensor (CS) or an eddy current sensor, pointed at the artifact. However, these sensors are designed for flat surface measurement. Therefore, measuring a target with a curved surface causes error. This is due to electric fields behaving differently between a flat and curved surface than between two flat surfaces. In this study, a laser is positioned incident to the cylindrical surface of the spindle, and a photodetector collects the total field produced by the diffraction around the target surface. The proposed sensor was compared with a CS within a range of 500 μm. The discrepancy between the proposed sensor and CS was 0.017% of the full range. Its sensing performance showed a resolution of 14 nm and a drift of less than 10 nm for 7 min of operation. This sensor was also used to measure dynamic characteristics of the spindle system (natural frequency 181.8 Hz, damping ratio 0.042) and spindle runout (22.0 μm at 2000 rpm). The combined standard uncertainty was estimated as 85.9 nm under current experiment conditions. It is anticipated that this measurement technique allows for in situ health monitoring of a precision spindle system in an accurate, convenient, and low cost manner.

  12. A curved edge diffraction-utilized displacement sensor for spindle metrology.

    Lee, ChaBum; Mahajan, Satish M; Zhao, Rui; Jeon, Seongkyul


    This paper presents a new dimensional metrological sensing principle for a curved surface based on curved edge diffraction. Spindle error measurement technology utilizes a cylindrical or spherical target artifact attached to the spindle with non-contact sensors, typically a capacitive sensor (CS) or an eddy current sensor, pointed at the artifact. However, these sensors are designed for flat surface measurement. Therefore, measuring a target with a curved surface causes error. This is due to electric fields behaving differently between a flat and curved surface than between two flat surfaces. In this study, a laser is positioned incident to the cylindrical surface of the spindle, and a photodetector collects the total field produced by the diffraction around the target surface. The proposed sensor was compared with a CS within a range of 500 μm. The discrepancy between the proposed sensor and CS was 0.017% of the full range. Its sensing performance showed a resolution of 14 nm and a drift of less than 10 nm for 7 min of operation. This sensor was also used to measure dynamic characteristics of the spindle system (natural frequency 181.8 Hz, damping ratio 0.042) and spindle runout (22.0 μm at 2000 rpm). The combined standard uncertainty was estimated as 85.9 nm under current experiment conditions. It is anticipated that this measurement technique allows for in situ health monitoring of a precision spindle system in an accurate, convenient, and low cost manner. PMID:27475601

  13. Tipping the spindle into the right position.

    Akhmanova, Anna; van den Heuvel, Sander


    The position of the mitotic spindle determines the cleavage plane in animal cells, but what controls spindle positioning? Kern et al. (2016. J. Cell Biol. demonstrate that the microtubule plus end-associated SKAP/Astrin complex participates in this process, possibly by affecting dynein-dependent pulling forces exerted on the tips of astral microtubules. PMID:27138251

  14. Mechanical stability of bipolar spindle assembly

    Malgaretti, Paolo; Muhuri, Sudipto


    Assembly and stability of mitotic spindle are governed by the interplay of various intra-cellular forces, e.g. the forces generated by motor proteins by sliding overlapping anti-parallel microtubules (MTs) polymerized from the opposite centrosomes, the interaction of kinetochores with MTs, and the interaction of MTs with the chromosome arms. We study the mechanical behavior and stability of spindle assembly within the framework of a minimal model which includes all these effects. For this model, we derive a closed-form analytical expression for the force acting between the centrosomes as a function of their separation distance and we show that an effective potential can be associated with the interactions at play. We obtain the stability diagram of spindle formation in terms of parameters characterizing the strength of motor sliding, repulsive forces generated by polymerizing MTs, and the forces arising out of the interaction of MTs with kinetochores. The stability diagram helps in quantifying the relative effects of the different interactions and elucidates the role of motor proteins in formation and inhibition of spindle structures during mitotic cell division. We also predict a regime of bistability for a certain parameter range, wherein the spindle structure can be stable for two different finite separation distances between centrosomes. This occurrence of bistability also suggests the mechanical versatility of such self-assembled spindle structures.

  15. An astral simulacrum of the central spindle accounts for normal, spindle-less, and anucleate cytokinesis in echinoderm embryos.

    Su, Kuan-Chung; Bement, William M; Petronczki, Mark; von Dassow, George


    Cytokinesis in animal cells depends on spindle-derived spatial cues that culminate in Rho activation, and thereby actomyosin assembly, in a narrow equatorial band. Although the nature, origin, and variety of such cues have long been obscure, one component is certainly the Rho activator Ect2. Here we describe the behavior and function of Ect2 in echinoderm embryos, showing that Ect2 migrates from spindle midzone to astral microtubules in anaphase and that Ect2 shapes the pattern of Rho activation in incipient furrows. Our key finding is that Ect2 and its binding partner Cyk4 accumulate not only at normal furrows, but also at furrows that form in the absence of associated spindle, midzone, or chromosomes. In all these cases, the cell assembles essentially the same cytokinetic signaling ensemble—opposed astral microtubules decorated with Ect2 and Cyk4. We conclude that if multiple signals contribute to furrow induction in echinoderm embryos, they likely converge on the same signaling ensemble on an analogous cytoskeletal scaffold. PMID:25298401

  16. Activities in the Dynamic Occupational Therapy Method

    Jô Benetton; Taís Quevedo Marcolino


    This paper addresses the concept and use of the instrument named ‘activities’ in occupational therapy, sustained by the propositions of the Dynamic Occupational Therapy Method (DOTM). Initially, we present general aspects related to the activities in the DOTM such as the option for the name ‘activities’, its conceptual definition, use as a tool, and active participation in the dynamic of triadic relationship. Further, it approaches the character of activities: therapeutic, educational and soc...

  17. Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex.

    An, Shuming; Kilb, Werner; Luhmann, Heiko J


    Self-generated neuronal activity originating from subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neural activity patterns and role of primary motor cortex (M1) in these early movements are still unknown. Combining voltage-sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7% of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts were uncorrelated to movements and these bursts had significantly fewer spikes and shorter burst duration. Focal electrical stimulation of layer V neurons in M1 mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity reliably elicited forepaw movements. We conclude that M1 is already involved in somatosensory information processing during early development. M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Only a fraction of M1 activity transients trigger motor responses directly. We suggest that both spontaneously occurring and sensory-evoked gamma and spindle bursts in M1 contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination. PMID:25122889

  18. The spindle protein CHICA mediates localization of the chromokinesin Kid to the mitotic spindle

    Santamaria, Anna; Nagel, Susanna; Sillje, Herman H W; Nigg, Erich A


    Microtubule-based motor proteins provide essential forces for bipolar organization of spindle microtubules and chromosome movement, prerequisites of chromosome segregation during the cell cycle. Here, we describe the functional characterization of a novel spindle protein, termed "CHICA," that was or

  19. New spindle morphogenesis model by Dynein,Nudel, and the spindle matrix

    Wei-Lih Lee; Patricia Wadsworth


    @@ It is well established that the mi-totic spindle, the organeile responsible for chromosome segregation during mitosis, is built from microtubules, motor proteins, and associated struc-tural and regulatory molecules. More controversial is the existence and identity of non-microtubule spindle components, collectively referred to as the matrix.

  20. The actin-binding ERM protein Moesin directly regulates spindle assembly and function during mitosis.

    Vilmos, Péter; Kristó, Ildikó; Szikora, Szilárd; Jankovics, Ferenc; Lukácsovich, Tamás; Kari, Beáta; Erdélyi, Miklós


    Ezrin-Radixin-Moesin proteins are highly conserved, actin-binding cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis by linking actin filaments to the plasma membrane. Recent studies demonstrated that the only Ezrin-Radixin-Moesin protein of Drosophila melanogaster, Moesin, is involved in mitotic spindle function through stabilizing cell shape and microtubules at the cell cortex. We previously observed that Moesin localizes to the mitotic spindle; hence, we tested for the biological significance of this surprising localization and investigated whether it plays a direct role in spindle function. To separate the cortical and spindle functions of Moesin during mitosis we combined cell biological and genetic methods. We used early Drosophila embryos, in which mitosis occurs in the absence of a cell cortex, and found in vivo evidence for the direct requirement of Moesin in mitotic spindle assembly and function. We also found that the accumulation of Moesin precedes the construction of the microtubule spindle, and the fusiform structure formed by Moesin persists even after the microtubules have disassembled. PMID:27006187

  1. Cep55 regulates spindle organization and cell cycle progression in meiotic oocyte.

    Xu, Zhao-Yang; Ma, Xue-Shan; Qi, Shu-Tao; Wang, Zhen-Bo; Guo, Lei; Schatten, Heide; Sun, Qing-Yuan; Sun, Ying-Pu


    Cep55 is a relatively novel member of the centrosomal protein family. Here, we show that Cep55 is expressed in mouse oocytes from the germinal vesicle (GV) to metaphase II (MII) stages. Immuostaining and confocal microscopy as well as time lapse live imaging after injection of mRNA encoding fusion protein of Cep55 and GFP identified that Cep55 was localized to the meiotic spindle, especially to the spindle poles at metaphase, while it was concentrated at the midbody in telophase in meiotic oocytes. Knockdown of Cep55 by specific siRNA injection caused the dissociation of γ-tubulin from the spindle poles, resulting in severely defective spindles and misaligned chromosomes, leading to metaphase I arrest and failure of first polar body (PB1) extrusion. Correspondingly, cyclin B accumulation and spindle assembly checkpoint (SAC) activation were observed in Cep55 knockdown oocytes. Our results suggest that Cep55 may act as an MTOC-associated protein regulating spindle organization, and thus cell cycle progression during mouse oocyte meiotic maturation. PMID:26582107

  2. High Temperature Resistant Exhaust Valve Spindle

    Bihlet, Uffe Ditlev

    O5 and Na2SO4 condense on the spindle, causing hot corrosion. Current industry standards can withstand service temperatures of up to 500°C for the spindle seat and 700°C for the spindle bottom. This project was tasked with increasing these temperatures 50°C each. Literature review as well as an in......-situ corrosion test revealed that the most resistant alloy in such an environment is Alloy 657 (Ni-based, 49 wt% Cr, 1.5 wt% Nb). This alloy is suitable for the spindle bottom, but not for the spindle seat, as it is too weak. Thermodynamic calculations suggested that it was possible to modify the chemistry of...... the current valve seat alloy, Alloy 718 (Ni-based, 19 wt% Cr, 18 wt% Fe, 5.1 wt% Nb, 3 wt% Mo, 1 wt% Ti and 0.6 wt% Al), and thereby to obtain a more hot corrosion resistant alloy. To validate these calculations, 16 Ni-based alloys, containing 40 wt% Cr and Nb, Ta and Ti in varying levels, were...

  3. Mechanical stability of bipolar spindle assembly

    Malgaretti, Paolo


    Assembly and stability of mitotic spindle is governed by the interplay of various intra-cellular forces, e.g. the forces generated by motor proteins by sliding overlapping anti-parallel microtubules (MTs) polymerized from the opposite centrosomes, the interaction of kinetochores with MTs, and the interaction of MTs with the chromosomes arms. We study the mechanical behavior and stability of spindle assembly within the framework of a minimal model which includes all these effects. For this model, we derive a closed--form analytical expression for the force acting between the centrosomes as a function of their separation distance and we show that an effective potential can be associated with the interactions at play. We obtain the stability diagram of spindle formation in terms of parameters characterizing the strength of motor sliding, repulsive forces generated by polymerizing MTs, and the forces arising out of interaction of MTs with kinetochores. The stability diagram helps in quantifying the relative effec...

  4. Functions of spindle check-point and its relationship to chromosome instability


    It is generally believed that the equal distribution of genetic materials to two daughter cells during mitosis is the key to cell health and development. During the dynamic process, spindle checkpoint plays a very important role in chromosome movements and final sister chromatid separation. The equal and precise segregation of chromosomes contributes to the genomic stability while aberrant separations result in chromosome instability that causes pathogenesis of certain diseases such as Down's syndrome and cancers. Kinetochore and its regulatory proteins consist of the spindle checkpoint and determine the spatial and temporal orders of chromosome segregation.

  5. Pattern Recognition With Adaptive-Thresholds For Sleep Spindle In High Density EEG Signals

    Gemignani, Jessica; Agrimi, Jacopo; Cheli, Enrico; Gemignani, Angelo; Laurino, Marco; Allegrini, Paolo; Landi, Alberto; Menicucci, Danilo


    Sleep spindles are electroencephalographic oscillations peculiar of non-REM sleep, related to neuronal mechanisms underlying sleep restoration and learning consolidation. Based on their very singular morphology, sleep spindles can be visually recognized and detected, even though this approach can lead to significant mis-detections. For this reason, many efforts have been put in developing a reliable algorithm for spindle automatic detection, and a number of methods, based on different techniques, have been tested via visual validation. This work aims at improving current pattern recognition procedures for sleep spindles detection by taking into account their physiological sources of variability. We provide a method as a synthesis of the current state of art that, improving dynamic threshold adaptation, is able to follow modification of spindle characteristics as a function of sleep depth and inter-subjects variability. The algorithm has been applied to physiological data recorded by a high density EEG in order to perform a validation based on visual inspection and on evaluation of expected results from normal night sleep in healthy subjects. PMID:26736332

  6. Sleep Spindles as Facilitators of Memory Formation and Learning

    Ulrich, Daniel


    Over the past decades important progress has been made in understanding the mechanisms of sleep spindle generation. At the same time a physiological role of sleep spindles is starting to be revealed. Behavioural studies in humans and animals have found significant correlations between the recall performance in different learning tasks and the amount of sleep spindles in the intervening sleep. Concomitant neurophysiological experiments showed a close relationship between sleep spindles and oth...

  7. On the Dynamics of Active Aging

    Johannes J. F. Schroots


    The conceptual basis of active aging is extended with a dynamic systems model, called Janus. The Janus model accounts for the life-course dynamics of simple and more complex growth and decline functions, on the strength of three principles. The first principle of transition states that the unitary lifespan trajectory of development and aging is the product of two complementary forces, growth and senescence, which are effective from conception until death. The first principle solves the tradit...

  8. Active Polar Two-Fluid Macroscopic Dynamics

    Pleiner, Harald; Svensek, Daniel; Brand, Helmut R.


    We study the dynamics of systems with a polar dynamic preferred direction. Examples include the pattern-forming growth of bacteria (in a solvent, shoals of fish (moving in water currents), flocks of birds and migrating insects (flying in windy air). Because the preferred direction only exists dynamically, but not statically, the macroscopic variable of choice is the macroscopic velocity associated with the motion of the active units. We derive the macroscopic equations for such a system and discuss novel static, reversible and irreversible cross-couplings connected to this second velocity. We find a normal mode structure quite different compared to the static descriptions, as well as linear couplings between (active) flow and e.g. densities and concentrations due to the genuine two-fluid transport derivatives. On the other hand, we get, quite similar to the static case, a direct linear relation between the stress tensor and the structure tensor. This prominent ``active'' term is responsible for many active effects, meaning that our approach can describe those effects as well. In addition, we also deal with explicitly chiral systems, which are important for many active systems. In particular, we find an active flow-induced heat current specific for the dynamic chiral polar order.

  9. Spindle cell lipoma of the posterior axilla: a case report

    Lee, Jee Young; Suh, Kyung Jin; Kim, Sang Yoon [Dongguk University Hospital, Cheonan (Korea, Republic of)


    Spindle cell lipoma is characterized by different cell components, mature adipocytes, spindle cells and collagen bundles, and it presents as a well-defined benign fatty mass on the posterior neck or upper back of middle aged men. As a result of the various ratios of non-adipose tissue, it is difficult to differentiate spindle cell lipoma from liposarcoma. To the best of our knowledge, the imaging features of spindle cell lipoma have not been reported in Korea. We report here on the imaging findings of a histologically confirmed spindle cell lipoma in the subcutaneous layer of the posterior axilla.

  10. Active Cyber Defense Dynamics Exhibiting Rich Phenomena

    Zheng, Ren; Xu, Shouhuai


    The Internet is a man-made complex system under constant attacks (e.g., Advanced Persistent Threats and malwares). It is therefore important to understand the phenomena that can be induced by the interaction between cyber attacks and cyber defenses. In this paper, we explore the rich phenomena that can be exhibited when the defender employs active defense to combat cyber attacks. To the best of our knowledge, this is the first study that shows that {\\em active cyber defense dynamics} (or more generally, {\\em cybersecurity dynamics}) can exhibit the bifurcation and chaos phenomena. This has profound implications for cyber security measurement and prediction: (i) it is infeasible (or even impossible) to accurately measure and predict cyber security under certain circumstances; (ii) the defender must manipulate the dynamics to avoid such {\\em unmanageable situations} in real-life defense operations.

  11. Impaired prefrontal sleep spindle regulation of hippocampal-dependent learning in older adults.

    Mander, Bryce A; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Ancoli-Israel, Sonia; Jagust, William J; Walker, Matthew P


    A hallmark feature of cognitive aging is a decline in the ability to form new memories. Parallel to these cognitive impairments are marked disruptions in sleep physiology. Despite recent evidence in young adults establishing a role for sleep spindles in restoring hippocampal-dependent memory formation, the possibility that disrupted sleep physiology contributes to age-related decline in hippocampal-dependent learning remains unknown. Here, we demonstrate that reduced prefrontal sleep spindles by over 40% in older adults statistically mediates the effects of old age on next day episodic learning, such that the degree of impaired episodic learning is explained by the extent of impoverished prefrontal sleep spindles. In addition, prefrontal spindles significantly predicted the magnitude of impaired next day hippocampal activation, thereby determining the influence of spindles on post-sleep learning capacity. These data support the hypothesis that disrupted sleep physiology contributes to age-related cognitive decline in later life, the consequence of which has significant treatment intervention potential. PMID:23901074

  12. On the dynamics of active aging.

    Schroots, Johannes J F


    The conceptual basis of active aging is extended with a dynamic systems model, called Janus. The Janus model accounts for the life-course dynamics of simple and more complex growth and decline functions, on the strength of three principles. The first principle of transition states that the unitary lifespan trajectory of development and aging is the product of two complementary forces, growth and senescence, which are effective from conception until death. The first principle solves the traditional problem of the age at which development ends and the process of aging starts. The second and third principles of peak capacity and peak time refer, respectively, to the impact of growth rate (peak capacity) and rate of senescence (peak time) on the life-course of dynamic systems. The validity of the Janus model is demonstrated by simulating the empirical lifespan trajectories of functional capacity, intelligence, and mortality. The Janus model contributes to the concept of active aging by underlining the dynamic limits of human nature, by stimulating effective policies for promoting active aging in the first half of life, and by emphasizing the growth potential of older people in the second half. PMID:22973306

  13. [Relationship between simulated weightlessness-induced muscle spindle change and muscle atrophy].

    Zhao, Xue-Hong; Fan, Xiao-Li


    One of the most important and urgent issues in the field of space medicine is to reveal the potential mechanism underlying the disused muscle atrophy during the weightlessness or microgravity environment. It will conduce to find out effective methods for the prevention and treatment of muscle atrophy during a long-term space flight. Increasing data show that muscle spindle discharges are significantly altered following the hindlimb unloading, suggesting a vital role in the progress of muscle atrophy. In the last decades, we have made a series of studies on changes in the morphological structure and function of muscle spindle following simulated weightlessness. This review will discuss our main results and related researches for understanding of muscle spindle activities during microgravity environment, which may provide a theoretic basis for effective prevention and treatment of muscle atrophy induced by weightlessness. PMID:23426520

  14. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

    Xia, Jingjing; Swiercz, Jakub M.; Bañón-Rodríguez, Inmaculada;


    Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we...... show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading to...... severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central...


    唐斌; 樊小力; 吴苏娣


    Objective To analyse the antinociceptive effect of red nucleus (RN) and its role in the antinociceptive effect of muscle spindle afferents. Methods The single units of RN or wide dynamic range (WDR) neuron in the spinal cord dorsal horn were extracelluarly recorded. The effects of RN stimulation on nociceptive responses (C-fibers-evoked responses, C-responses) of WDR neurons were observed. The influence of muscle spindle afferents elicited by intravenous administration of succinylcholine (Sch) on the spontaneous discharge of RN neurons and on C-responses of WDR neurons were observed. The effect of muscle spindle afferents on C-responses of WDR neurons after unilateral lesions of RN was also observed. Results Electrical stimulation of the RN produced a significantly inhibitory effect on the nociceptive responses of WDR neurons. RN neurons were excited by muscle spindle afferents. Muscle spindle afferents significantly inhibited C-response of WDR neurons and this inhibitory effect was reduced by lesions of RN. Conclusion RN neurons have a significant antinociceptive effect and might be involved in the antinociceptive effects elicited by muscle spindle afferents.

  16. Breast spindle cell tumours: about eight cases

    Abd El All Howayda S


    Full Text Available Abstract Background Breast spindle cell tumours (BSCTs, although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC, histopathology and immunohistochemistry (IHC in differentiating BSCTs. Methods FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. Results FNAC defined the tumors as benign (n = 4, suspicious (n = 2 and malignant (n = 3, based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5 and malignant (n = 3. In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma. For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma. In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. Conclusion FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.

  17. Material Choice for spindle of machine tools

    The requirements of contemporary industry and the flashing development of modern sciences impose restrictions on the majority of the elements of machines; the resulting financial constraints can be satisfied by a better output of the production equipment. As for those concerning the design, the resistance and the correct operation of the product, these require the development of increasingly precise parts, therefore the use of increasingly powerful tools [5]. The precision of machining and the output of the machine tools are generally determined by the precision of rotation of the spindle, indeed, more this one is large more the dimensions to obtain are in the zone of tolerance and the defects of shape are minimized. During the development of the machine tool, the spindle which by definition is a rotating shaft receiving and transmitting to the work piece or the cutting tool the rotational movement, must be designed according to certain optimal parameters to be able to ensure the precision required. This study will be devoted to the choice of the material of the spindle fulfilling the imposed requirements of precision.

  18. Spindle cell carcinoma of the nasal cavity

    Mark D DeLacure


    Full Text Available Spindle cell carcinoma (SpCC is a unique variant of squamous cell carcinoma (SCC. SpCC confined to the nasal cavity is extremely rare, with only one case having been previously reported. We present a case report of nasal cavity SpCC and review the literature on this rare entity. A 29-year-old male presented with intermittent epistaxis from the left nasal cavity. On physical examination, the patient had an ulcerated mass in the left nasal vestibule and a biopsy showed a proliferation of spindle and epitheliod cells. The patient underwent wide local excision of the mass via a lateral alotomy approach and reconstruction with a composite conchal bowl skin and cartilage graft. Histologically, the mass had dyplastic squamous epithelium and spindle-shaped cells admixed with epitheliod cells. Immunohistochemistry was only positive for pancytokeratin AE1/AE3 and vimentin. Six months after surgery, the patient continues to have no evidence of disease. On literature review, only one previous case of SpCC confined to the nasal cavity was identified. We present a rare case of nasal cavity SpCC. No definite treatment protocol exists for this unique entity, but we believe that this tumor should primarily be treated with aggressive, wide local excision. Adjuvant radiation and/or chemotherapy have also been used anecdotally.

  19. Dynamic active earth pressure on retaining structures

    Deepankar Choudhury; Santiram Chatterjee


    Earth-retaining structures constitute an important topic of research in civil engineering, more so under earthquake conditions. For the analysis and design of retaining walls in earthquake-prone zones, accurate estimation of dynamic earth pressures is very important. Conventional methods either use pseudo-static approaches of analysis even for dynamic cases or a simple single-degree of freedom model for the retaining wall–soil system. In this paper, a simplified two-degree of freedom mass–spring–dashpot (2-DOF) dynamic model has been proposed to estimate the active earth pressure at the back of the retaining walls for translation modes of wall movement under seismic conditions. The horizontal zone of influence on dynamic earth force on the wall is estimated. Results in terms of displacement, velocity and acceleration-time history are presented for some typical cases, which show the final movement of the wall in terms of wall height, which is required for the design. The non-dimensional design chart proposed in the present study can be used to compute the total dynamic earth force on the wall under different input ground motion and backfill conditions. Finally, the results obtained have been compared with those of the available Scott model and the merits of the present results have been discussed.

  20. Presence of Meiotic Spindles Indicates Early Cleavage of Embryos


    Objective To assess whether the detection of the meiotic spindle could anticipate the appearance of early cleavage.Methods Oocytes were obtained from stimulated ovaries of consenting patients undergoing oocytes retrieval for ICSI.Spindles were imaged with the Polscope.After ICSI,oocytes with or without spindles were cultured for examination of early cleavage and embryo development.A total of 328 oocytes from 50 cycles were examined with the Polscope and inseminated by ICSI.Results Spindles were imaged in 81.7% of oocytes.After ICSI,more oocytes with spindles (78.4%) fertilized normally than oocytes without spindles (53.3%)(P<0.001).At 25-27 h post ICSI.more fertilized oocytes developed from oocytes with spindles (81.9%) were detected early cleavage than those from oocytes without spindles(28.1%)(P<0.001).Significantly more embryos with early cleavage (82.2%) developed to high quality embryos at d 3 compared with the embryos without early cleavage(48.3%)(P=0.001).The value of rs related to the relationship between spindles and early cleavage was 0.420(P<0.0001).Conclusion The existing of the early cleavage may have a predictive value on the opportunity of high quality embryos and the existing of the spindle may have a predictive value in the appearance of early cleavage.

  1. Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A

    Wolthuis, Rob; Clay-Farrace, Lori; van Zon, Wouter; Yekezare, Mona; Koop, Lars; Ogink, Janneke; Medema, Rene; Pines, Jonathon


    Successful mitosis requires the right protein be degraded at the right time. Central to this is the spindle checkpoint that prevents the destruction of securin and cyclin 131 when there are improperly attached chromosomes. The principal target of the checkpoint is Cdc20, which activates the anaphase

  2. Dynamic adsorption of radon on activated carbon

    The adsorption of 222Rn from air onto activated carbon was studied over the range 0 to 550C. A sharp pulse of radon was injected into an air stream that flowed through a bed of activated carbon. The radon concentration in the exit from the column was continuously monitored using a zinc sulfide α-scintillation flow cell. Elution curves were analyzed to determine the dynamic adsorption coefficient and the number of theoretical stages. Five types of activated carbon were tested and the dynamic adsorption coefficient was found to increase linearly with surface area in the range 1000 to 1300 m2g-1. The adsorptive capacity of activated carbon was reduced by up to 30% if the entering gas was saturated with water vapor and the bed was initially dry. If the bed was allowed to equilibrate with saturated air, the adsorptive capacity was too low to be of practical use. The minimum height equivalent to a theoretical stage (HETS) was about four times the particle diameter and occurred at superficial velocities within the range 0.002 to 0.02 m s-1. For superficial velocities above 0.05 m s-1, the HETS was determined by the rate of mass transfer. The application of these results to the design of activated carbon systems for radon retention is discussed

  3. Coordinated Alpha and Gamma Control of Muscles and Spindles in Movement and Posture

    Si eLi


    Full Text Available Mounting evidence suggests that both α and γ motoneurons are active during movement and posture, but how does the central motor system coordinate the α-γ controls in these tasks remains sketchy due to lack of in vivo data. Here a computational model of α-γ control of muscles and spindles was used to investigate α-γ integration and coordination for movement and posture. The model comprised physiologically realistic spinal circuitry, muscles, proprioceptors, and skeletal biomechanics. In the model, we divided the cortical descending commands into static and dynamic sets, where static commands (static α and γ were for posture maintenance and dynamic commands (dynamic α and γ were responsible for movement. We matched our model to human reaching movement data by straightforward adjustments of descending commands derived from either minimal-jerk trajectories or human EMGs. The matched movement showed smooth reach-to-hold trajectories qualitatively close to human behaviors, and the reproduced EMGs showed the classic tri-phasic patterns. In particular, the function of dynamic γ was to gate the αd command at the propriospinal neurons (PN such that antagonistic muscles can accelerate or decelerate the limb with proper timing. Independent control of joint position and stiffness could be achieved by adjusting static commands. Deefferentation in the model indicated that accurate static commands of static α and γ are essential to achieve stable terminal posture precisely, and that the dynamic γ command is as important as the dynamic α command in controlling antagonistic muscles for desired movements. Deafferentation in the model showed that losing proprioceptive afferents mainly affected the termination position of movement, similar to the abnormal behaviors observed in human and animals. Our results illustrated that tuning the simple forms of α-γ commands can reproduce a range of human reach-to-hold movements, and it is necessary to

  4. Activities in the Dynamic Occupational Therapy Method

    Jô Benetton


    Full Text Available This paper addresses the concept and use of the instrument named ‘activities’ in occupational therapy, sustained by the propositions of the Dynamic Occupational Therapy Method (DOTM. Initially, we present general aspects related to the activities in the DOTM such as the option for the name ‘activities’, its conceptual definition, use as a tool, and active participation in the dynamic of triadic relationship. Further, it approaches the character of activities: therapeutic, educational and social qualities, which distinguish this peculiar occupational therapy. Moreover, the paper highlights the use of activities as a tool, both as a central element of the processes that should underpin clinical reasoning (observation, information, association, setting up space of historicity, and construction of narrative, and as an element belonging to diagnostic procedures, to the course of clinical process, and to evaluation. Finally, we present our understanding of what we call resources in DOTM, and its intrinsic connection with the possibility of performing ‘activities’. For the creation of DOTM, occupational therapy, as a practice focused on the uniqueness of the case, was made the object of study in order to promote knowledge construction. The conceptual and instrumental framework presented in this work held this effort. We hope that this study could be useful for initial and continuing training in Occupational Therapy as well as for enriching the debate on the use of ‘activities’ in our profession.

  5. A Protein Interaction Map of the Mitotic Spindle

    Wong, Jonathan; Nakajima, Yuko; Westermann, Stefan; Shang, Ching; Kang, Jung-seog; Goodner, Crystal; Houshmand, Pantea; Fields, Stanley; Chan, Clarence S.M.; Drubin, David; Barnes, Georjana; Hazbun, Tony


    The mitotic spindle consists of a complex network of proteins that segregates chromosomes in eukaryotes. To strengthen our understanding of the molecular composition, organization, and regulation of the mitotic spindle, we performed a system-wide two-hybrid screen on 94 proteins implicated in spindle function in Saccharomyces cerevisiae. We report 604 predominantly novel interactions that were detected in multiple screens, involving 303 distinct prey proteins. We uncovered a pattern of extens...

  6. EEG alpha spindles and prolonged brake reaction times during auditory distraction in an on-road driving study.

    Sonnleitner, Andreas; Treder, Matthias Sebastian; Simon, Michael; Willmann, Sven; Ewald, Arne; Buchner, Axel; Schrauf, Michael


    Driver distraction is responsible for a substantial number of traffic accidents. This paper describes the impact of an auditory secondary task on drivers' mental states during a primary driving task. N=20 participants performed the test procedure in a car following task with repeated forced braking on a non-public test track. Performance measures (provoked reaction time to brake lights) and brain activity (EEG alpha spindles) were analyzed to describe distracted drivers. Further, a classification approach was used to investigate whether alpha spindles can predict drivers' mental states. Results show that reaction times and alpha spindle rate increased with time-on-task. Moreover, brake reaction times and alpha spindle rate were significantly higher while driving with auditory secondary task opposed to driving only. In single-trial classification, a combination of spindle parameters yielded a median classification error of about 8% in discriminating the distracted from the alert driving. Reduced driving performance (i.e., prolonged brake reaction times) during increased cognitive load is assumed to be indicated by EEG alpha spindles, enabling the quantification of driver distraction in experiments on public roads without verbally assessing the drivers' mental states. PMID:24144496

  7. A Dynamic Absorber With Active Vibration Control

    Huang, S.-J.; Lian, R.-J.


    The design and construction of a dynamic absorber incorporating active vibration control is described. The absorber is a two-degrees-of-freedom spring — lumped mass system sliding on a guide pillar, with two internal vibration disturbance sources. Both the main mass and the secondary absorber mass are acted on by DC servo motors, respectively, to suppress the vibration amplitude. The state variable technique is used to model this dynamic system and a decoupling PID control method is used. First, the discrete time state space model is identified by using the commercial software MATLAB. Then the decoupling controller of this multi-input/multi-output system is derived from the identified model. Finally the results of some experiments are presented. The experimental results show that the system is effective in suppressing vibration. Also, the performance of this control strategy for position tracking control is evaluated based on experimental data.

  8. A pathway containing the Ipl1/Aurora protein kinase and the spindle midzone protein Ase1 regulates yeast spindle assembly

    Kotwaliwale, Chitra V.; Frei, Stéphanie Buvelot; Stern, Bodo M.; Biggins, Sue


    It is critical to elucidate the pathways that mediate spindle assembly and therefore ensure accurate chromosome segregation during cell division. Our studies of a unique allele of the budding yeast Ipl1/Aurora protein kinase revealed that it is required for centrosome-mediated spindle assembly in the absence of the BimC motor protein Cin8. In addition, we found that the Ase1 spindle midzone-associated protein is required for bipolar spindle assembly. The cin8 ipl1 and cin8 ase1 double mutant ...

  9. Small molecule inhibitor of formin homology 2 domains (SMIFH2 reveals the roles of the formin family of proteins in spindle assembly and asymmetric division in mouse oocytes.

    Hak-Cheol Kim

    Full Text Available Dynamic actin reorganization is the main driving force for spindle migration and asymmetric cell division in mammalian oocytes. It has been reported that various actin nucleators including Formin-2 are involved in the polarization of the spindle and in asymmetric cell division. In mammals, the formin family is comprised of 15 proteins. However, their individual roles in spindle migration and/or asymmetric division have not been elucidated yet. In this study, we employed a newly developed inhibitor for formin family proteins, small molecule inhibitor of formin homology 2 domains (SMIFH2, to assess the functions of the formin family in mouse oocyte maturation. Treatment with SMIFH2 during in vitro maturation of mouse oocytes inhibited maturation by decreasing cytoplasmic and cortical actin levels. In addition, treatment with SMIFH2, especially at higher concentrations (500 μM, impaired the proper formation of meiotic spindles, indicating that formins play a role in meiotic spindle formation. Knockdown of the mDia2 formins caused a similar decrease in oocyte maturation and abnormal spindle morphology, mimicking the phenotype of SMIFH2-treated cells. Collectively, these results suggested that besides Formin-2, the other proteins of the formin, including mDia family play a role in asymmetric division and meiotic spindle formation in mammalian oocytes.

  10. Control of position and movement is simplified by combined muscle spindle and Golgi tendon organ feedback.

    Kistemaker, Dinant A; Van Soest, Arthur J Knoek; Wong, Jeremy D; Kurtzer, Isaac; Gribble, Paul L


    Whereas muscle spindles play a prominent role in current theories of human motor control, Golgi tendon organs (GTO) and their associated tendons are often neglected. This is surprising since there is ample evidence that both tendons and GTOs contribute importantly to neuromusculoskeletal dynamics. Using detailed musculoskeletal models, we provide evidence that simple feedback using muscle spindles alone results in very poor control of joint position and movement since muscle spindles cannot sense changes in tendon length that occur with changes in muscle force. We propose that a combination of spindle and GTO afferents can provide an estimate of muscle-tendon complex length, which can be effectively used for low-level feedback during both postural and movement tasks. The feasibility of the proposed scheme was tested using detailed musculoskeletal models of the human arm. Responses to transient and static perturbations were simulated using a 1-degree-of-freedom (DOF) model of the arm and showed that the combined feedback enabled the system to respond faster, reach steady state faster, and achieve smaller static position errors. Finally, we incorporated the proposed scheme in an optimally controlled 2-DOF model of the arm for fast point-to-point shoulder and elbow movements. Simulations showed that the proposed feedback could be easily incorporated in the optimal control framework without complicating the computation of the optimal control solution, yet greatly enhancing the system's response to perturbations. The theoretical analyses in this study might furthermore provide insight about the strong physiological couplings found between muscle spindle and GTO afferents in the human nervous system. PMID:23100138

  11. Dynamics of two interacting active Janus particles

    Bayati, Parvin; Najafi, Ali


    Starting from a microscopic model for a spherically symmetric active Janus particle, we study the interactions between two such active motors. The ambient fluid mediates a long range hydrodynamic interaction between two motors. This interaction has both direct and indirect hydrodynamic contributions. The direct contribution is due to the propagation of fluid flow that originated from a moving motor and affects the motion of the other motor. The indirect contribution emerges from the re-distribution of the ionic concentrations in the presence of both motors. Electric force exerted on the fluid from this ionic solution enhances the flow pattern and subsequently changes the motion of both motors. By formulating a perturbation method for very far separated motors, we derive analytic results for the translation and rotational dynamics of the motors. We show that the overall interaction at the leading order modifies the translational and rotational speeds of motors which scale as O (" separators=" [ 1 / D ] 3 ) and O (" separators=" [ 1 / D ] 4 ) with their separation, respectively. Our findings open up the way for studying the collective dynamics of synthetic micro-motors.

  12. IL-6 and mouse oocyte spindle.

    Jashoman Banerjee

    Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

  13. Sleep spindles and intelligence: evidence for a sexual dimorphism

    Ujma, P.P.; Konrad, B.N.; Genzel, L.; Bleifuss, A.; Simor, P.; Potari, A.; Kormendi, J.; Gombos, F.; Steiger, A.; Bodizs, R.; Dresler, M.


    Sleep spindles are thalamocortical oscillations in nonrapid eye movement sleep, which play an important role in sleep-related neuroplasticity and offline information processing. Sleep spindle features are stable within and vary between individuals, with, for example, females having a higher number o

  14. Sleep Spindles as Biomarker for Early Detection of Neurodegenerative Disorders


    The present invention relates to the use of sleep spindles as a novel biomarker for early diagnosis of synucleinopathies, in particular Parkinson's disease (PD). The method is based on automatic detection of sleep spindles. The method may be combined with measurements of one or more further...

  15. Attachment issues : kinetochore transformations and spindle checkpoint silencing

    Etemad, Banafsheh; Kops, Geert Jpl


    Cell division culminates in the segregation of duplicated chromosomes in opposite directions prior to cellular fission. This process is guarded by the spindle assembly checkpoint (SAC), which prevents the anaphase of cell division until stable connections between spindle microtubules and the kinetoc

  16. Combining time-frequency and spatial information for the detection of sleep spindles

    Christian eO'Reilly


    Full Text Available EEG sleep spindles are short (0.5-2.0 s bursts of activity in the 11-16 Hz band occurring during non-rapid eye movement (NREM sleep. This sporadic activity is thought to play a role in memory consolidation, brain plasticity, and protection of sleep integrity. Many automatic detectors have been proposed to assist or replace experts for sleep spindle scoring. However, these algorithms usually detect too many events making it difficult to achieve a good tradeoff between sensitivity (Se and false detection rate (FDr. In this work, we propose a semi-automatic detector comprising a sensitivity phase based on well-established criteria followed by a specificity phase using spatial and spectral criteria.In the sensitivity phase, selected events are those which amplitude in the 10 – 16 Hz band and spectral ratio characteristics both reject a null hypothesis (p <0.1 stating that the considered event is not a spindle. This null hypothesis is constructed from events occurring during rapid eye movement (REM sleep epochs. In the specificity phase, a hierarchical clustering of the selected candidates is done based on events’ frequency and spatial position along the anterior-posterior axis. Only events from the classes grouping most (at least 80% spindles scored by an expert are kept. We obtain Se = 93.2% and FDr = 93.0% in the first phase and Se = 85.4% and FDr = 86.2% in the second phase. For these two phases, Matthew’s correlation coefficients are respectively 0.228 and 0.324. Results suggest that spindles are defined by specific spatio-spectral properties and that automatic detection methods can be improved by considering these features.

  17. The role of p53 in the response to mitotic spindle damage

    The p53 tumour suppressor protein has defined roles in G1/S and G2/M cell cycle checkpoint in response to a range of cellular stresses including DNA damage, dominant oncogene expression, hypoxia, metabolic changes and viral infection. In addition to these responses, p53 can also be activated when damage occurs to the mitotic spindle. Initially, spindle damage activates a p53-independent checkpoint which functions at the metaphase-anaphase transition and prevents cells from progressing through mitosis until the completion of spindle formation. Cells eventually escape from this block (a process termed 'mitotic slippage'), and an aberrant mitosis ensues in which sister chromatids fail to segregate properly. After a delay period, p53 responds to this mitotic failure by instituting a G1-like growth arrest, with an intact nucleus containing 4N DNA, but without the cells undergoing division. Cells lacking wild-type p53 are still able to arrest transiently at mitosis, and also fail to undergo division, underscoring that the delay in mitosis is p53-independent. However, these cells are not prevented from re-entering the cell cycle and can reduplicate their DNA unchecked, leading to polyploidy. Additionally, p53-null cells which experience spindle failure often show the appearance of micronuclei arising from poorly segregated chromosomes which have de-condensed and been enclosed in a nuclear envelope. The ability of p53 to prevent their formation suggests an additional G2 involvement which prevents nuclear breakdown prior to mitosis. The molecular mechanism by which p53 is able to sense mitotic failure is still unknown, but may be linked to the ability of p53 to regulate duplication of the centrosome, the organelle which nucleates spindle formation. (authors)

  18. Uncovering the Molecular Machinery of the Human Spindle-An Integration of Wet and Dry Systems Biology

    Rojas, Ana M.; Santamaria, Anna; Malik, Rainer;


    The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is dif...

  19. Polyglutamylated Tubulin Binding Protein C1orf96/CSAP Is Involved in Microtubule Stabilization in Mitotic Spindles

    Ohta, Shinya; Hamada, Mayako; Sato, Nobuko; Toramoto, Iyo


    The centrosome-associated C1orf96/Centriole, Cilia and Spindle-Associated Protein (CSAP) targets polyglutamylated tubulin in mitotic microtubules (MTs). Loss of CSAP causes critical defects in brain development; however, it is unclear how CSAP association with MTs affects mitosis progression. In this study, we explored the molecular mechanisms of the interaction of CSAP with mitotic spindles. Loss of CSAP caused MT instability in mitotic spindles and resulted in mislocalization of Nuclear protein that associates with the Mitotic Apparatus (NuMA), with defective MT dynamics. Thus, CSAP overload in the spindles caused extensive MT stabilization and recruitment of NuMA. Moreover, MT stabilization by CSAP led to high levels of polyglutamylation on MTs. MT depolymerization by cold or nocodazole treatment was inhibited by CSAP binding. Live-cell imaging analysis suggested that CSAP-dependent MT-stabilization led to centrosome-free MT aster formation immediately upon nuclear envelope breakdown without γ-tubulin. We therefore propose that CSAP associates with MTs around centrosomes to stabilize MTs during mitosis, ensuring proper bipolar spindle formation and maintenance. PMID:26562023

  20. Gem GTPase acts upstream Gmip/RhoA to regulate cortical actin remodeling and spindle positioning during early mitosis.

    Andrieu, Guillaume; Quaranta, Muriel; Leprince, Corinne; Cuvillier, Olivier; Hatzoglou, Anastassia


    Gem is a small guanosine triphosphate (GTP)-binding protein within the Ras superfamily, involved in the regulation of voltage-gated calcium channel activity and cytoskeleton reorganization. Gem overexpression leads to stress fiber disruption, actin and cell shape remodeling and neurite elongation in interphase cells. In this study, we show that Gem plays a crucial role in the regulation of cortical actin cytoskeleton that undergoes active remodeling during mitosis. Ectopic expression of Gem leads to cortical actin disruption and spindle mispositioning during metaphase. The regulation of spindle positioning by Gem involves its downstream effector Gmip. Knockdown of Gmip rescued Gem-induced spindle phenotype, although both Gem and Gmip accumulated at the cell cortex. In addition, we implicated RhoA GTPase as an important effector of Gem/Gmip signaling. Inactivation of RhoA by overexpressing dominant-negative mutant prevented normal spindle positioning. Introduction of active RhoA rescued the actin and spindle positioning defects caused by Gem or Gmip overexpression. These findings demonstrate a new role of Gem/Gmip/RhoA signaling in cortical actin regulation during early mitotic stages. PMID:25173885

  1. Dynamic response of active twist rotor blades

    Cesnik, Carlos E. S.; Shin, Sang Joon; Wilbur, Matthew L.


    Dynamic characteristics of active twist rotor (ATR) blades are investigated analytically and experimentally in this paper. The ATR system is intended for vibration and potentially for noise reductions in helicopters through individual blade control. An aeroelastic model is developed to identify frequency response characteristics of the ATR blade with integral, generally anisotropic, strain actuators embedded in its composite construction. An ATR prototype blade was designed and manufactured to experimentally study the vibration reduction capabilities of such systems. Several bench and hover tests were conducted and those results are presented and discussed here. Selected results on sensitivity of the ATR system to collective setting (i.e. blade loading), blade rpm (i.e. centrifugal force and blade station velocity), and media density (i.e. altitude) are presented. They indicated that the twist actuation authority of the ATR blade is independent of the collective setting up to approximately 10P, and dependent on rotational speed and altitude near the torsional resonance frequency due to its dependency on the aerodynamic damping. The proposed model captures very well the physics and sensitivities to selected test parameters of the ATR system. The numerical result of the blade torsional loads show an average error of 20% in magnitude and virtually no difference in phase for the blade frequency response. Overall, the active blade model is in very good agreement with the experiments and can be used to analyze and design future active helicopter blade systems.

  2. New activity pattern in human interactive dynamics

    Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni


    We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

  3. High-speed AMB machining spindle model updating and model validation

    Wroblewski, Adam C.; Sawicki, Jerzy T.; Pesch, Alexander H.


    High-Speed Machining (HSM) spindles equipped with Active Magnetic Bearings (AMBs) have been envisioned to be capable of automated self-identification and self-optimization in efforts to accurately calculate parameters for stable high-speed machining operation. With this in mind, this work presents rotor model development accompanied by automated model-updating methodology followed by updated model validation. The model updating methodology is developed to address the dynamic inaccuracies of the nominal open-loop plant model when compared with experimental open-loop transfer function data obtained by the built in AMB sensors. The nominal open-loop model is altered by utilizing an unconstrained optimization algorithm to adjust only parameters that are a result of engineering assumptions and simplifications, in this case Young's modulus of selected finite elements. Minimizing the error of both resonance and anti-resonance frequencies simultaneously (between model and experimental data) takes into account rotor natural frequencies and mode shape information. To verify the predictive ability of the updated rotor model, its performance is assessed at the tool location which is independent of the experimental transfer function data used in model updating procedures. Verification of the updated model is carried out with complementary temporal and spatial response comparisons substantiating that the updating methodology is effective for derivation of open-loop models for predictive use.

  4. Topography of age-related changes in sleep spindles.

    Martin, Nicolas; Lafortune, Marjolaine; Godbout, Jonathan; Barakat, Marc; Robillard, Rebecca; Poirier, Gaétan; Bastien, Célyne; Carrier, Julie


    Aging induces multiple changes to sleep spindles, which may hinder their alleged functional role in memory and sleep protection mechanisms. Brain aging in specific cortical regions could affect the neural networks underlying spindle generation, yet the topography of these age-related changes is currently unknown. In the present study, we analyzed spindle characteristics in 114 healthy volunteers aged between 20 and 73 years over 5 anteroposterior electroencephalography scalp derivations. Spindle density, amplitude, and duration were higher in young subjects than in middle-aged and elderly subjects in all derivations, but the topography of age effects differed drastically. Age-related decline in density and amplitude was more prominent in anterior derivations, whereas duration showed a posterior prominence. Age groups did not differ in all-night spindle frequency for any derivation. These results show that age-related changes in sleep spindles follow distinct topographical patterns that are specific to each spindle characteristic. This topographical specificity may provide a useful biomarker to localize age-sensitive changes in underlying neural systems during normal and pathological aging. PMID:22809452

  5. Sleep spindling and fluid intelligence across adolescent development: sex matters

    Róbert eBódizs


    Full Text Available Evidence supports the intricate relationship between sleep electroencephalogram (EEG spindling and cognitive abilities in children and adults. Although sleep EEG changes during adolescence index fundamental brain reorganization, a detailed analysis of sleep spindling and the spindle-intelligence relationship was not yet provided for adolescents. Therefore, adolescent development of sleep spindle oscillations were studied in a home polysomnographic study focusing on the effects of chronological age and developmentally acquired overall mental efficiency (fluid IQ with sex as a potential modulating factor. Subjects were 24 healthy adolescents (12 males with an age range of 15–22 years (mean: 18 years and fluid IQ of 91-126 (mean: 104.12, Raven Progressive Matrices Test. Slow spindles (SSs and fast spindles (FSs were analyzed in 21 EEG derivations by using the individual adjustment method. A significant age-dependent increase in average FS density (r = .57; p = .005 was found. Moreover, fluid IQ correlated with FS density (r = .43; p = .04 and amplitude (r = .41; p = .049. The latter effects were entirely driven by particularly reliable FS-IQ correlations in females [r = .80 (p = .002 and r = .67 (p = .012, for density and amplitude, respectively]. Region-specific analyses revealed that these correlations peak in the fronto-central regions. The control of the age-dependence of FS measures and IQ scores did not considerably reduce the spindle-IQ correlations with respect to FS density. The only positive spindle-index of fluid IQ in males turned out to be the frequency of FSs (r = .60, p = .04. Increases in FS density during adolescence may index reshaped structural connectivity related to white matter maturation in the late developing human brain. The continued development over this age range of cognitive functions is indexed by specific measures of sleep spindling unravelling gender differences in adolescent brain maturation and perhaps cognitive

  6. The kinesin-13 KLP10A motor regulates oocyte spindle length and affects EB1 binding without altering microtubule growth rates

    Kevin K. Do


    Full Text Available Kinesin-13 motors are unusual in that they do not walk along microtubules, but instead diffuse to the ends, where they remove tubulin dimers, regulating microtubule dynamics. Here we show that Drosophila kinesin-13 klp10A regulates oocyte meiosis I spindle length and is haplo-insufficient – KLP10A, reduced by RNAi or a loss-of-function P element insertion mutant, results in elongated and mispositioned oocyte spindles, and abnormal cortical microtubule asters and aggregates. KLP10A knockdown by RNAi does not significantly affect microtubule growth rates in oocyte spindles, but, unexpectedly, EB1 binding and unbinding are slowed, suggesting a previously unobserved role for kinesin-13 in mediating EB1 binding interactions with microtubules. Kinesin-13 may regulate spindle length both by disassembling subunits from microtubule ends and facilitating EB1 binding to plus ends. We also observe an increased number of paused microtubules in klp10A RNAi knockdown spindles, consistent with a reduced frequency of microtubule catastrophes. Overall, our findings indicate that reduced kinesin-13 decreases microtubule disassembly rates and affects EB1 interactions with microtubules, rather than altering microtubule growth rates, causing spindles to elongate and abnormal cortical microtubule asters and aggregates to form.

  7. Microsleeps are Associated with Stage-2 Sleep Spindles from Hippocampal-Temporal Network.

    Jonmohamadi, Yaqub; Poudel, Govinda R; Innes, Carrie C R H; Jones, Richard D


    Behavioral microsleeps are associated with complete disruption of responsiveness for [Formula: see text][Formula: see text]s to 15[Formula: see text]s. They can result in injury or death, especially in transport and military sectors. In this study, EEGs were obtained from five nonsleep-deprived healthy male subjects performing a 1[Formula: see text]h 2D tracking task. Microsleeps were detected in all subjects. Microsleep-related activities in the EEG were detected, characterized, separated from eye closure-related activity, and, via source-space-independent component analysis and power analysis, the associated sources were localized in the brain. Microsleeps were often, but not always, found to be associated with strong alpha-band spindles originating bilaterally from the anterior temporal gyri and hippocampi. Similarly, theta-related activity was identified as originating bilaterally from the frontal-orbital cortex. The alpha spindles were similar to sleep spindles in terms of frequency, duration, and amplitude-profile, indicating that microsleeps are equivalent to brief instances of Stage-2 sleep. PMID:27033540

  8. Cell adhesion molecule control of planar spindle orientation.

    Tuncay, Hüseyin; Ebnet, Klaus


    Polarized epithelial cells align the mitotic spindle in the plane of the sheet to maintain tissue integrity and to prevent malignant transformation. The orientation of the spindle apparatus is regulated by the immobilization of the astral microtubules at the lateral cortex and depends on the precise localization of the dynein-dynactin motor protein complex which captures microtubule plus ends and generates pulling forces towards the centrosomes. Recent developments indicate that signals derived from intercellular junctions are required for the stable interaction of the dynein-dynactin complex with the cortex. Here, we review the molecular mechanisms that regulate planar spindle orientation in polarized epithelial cells and we illustrate how different cell adhesion molecules through distinct and non-overlapping mechanisms instruct the cells to align the mitotic spindle in the plane of the sheet. PMID:26698907

  9. The deafferented reticular thalamic nucleus generates spindle rhythmicity.

    Steriade, M; Domich, L; Oakson, G; Deschênes, M


    The hypothesis that nucleus reticularis thalami (RE) is the generator of spindle rhythmicity during electroencephalogram (EEG) synchronization was tested in acutely prepared cats. Unit discharges and focal waves were extracellularly recorded in the rostral pole of RE nucleus, which was completely disconnected by transections from all other thalamic nuclei. In some experiments, additional transections through corona radiata created a triangular island in which the rostral RE pole survived with the caudate nucleus, putamen, basal forebrain nuclei, prepyriform area, and the adjacent cortex. Similar results were obtained in two types of experiments: brain stem-transected preparations that exhibited spontaneous spindle sequences, and animals under ketamine anesthesia in which transient spindling was repeatedly precipitated during recording by very low doses of a short-acting barbiturate. Both spindle-related rhythms (7- to 16-Hz waves grouped in sequences that recur with a rhythm of 0.1-0.3 Hz) are seen in focal recordings of the deafferented RE nucleus. The presence of spindling rhythmicity in the disconnected RE nucleus contrasts with total absence of spindles in cortical EEG leads and in thalamic recordings behind the transection. Oscillations within the same frequency range as that of spontaneous spindles can be evoked in the deafferented RE nucleus by subcortical white matter stimulation. In deafferented RE cells, the burst structure consists of an initially biphasic acceleration-deceleration pattern, eventually leading to a long-lasting tonic tail. Quantitative group data show that the burst parameters of disconnected RE cells are very similar to those of RE neurons with intact connections. In the deafferented RE nucleus, spike bursts of RE neurons recur periodically (0.1-0.3 Hz) in close time-relation with simultaneously recorded focal spindle sequences. The burst occurrence of deafferented RE cells is greatly reduced after systemic administration of bicuculline

  10. Individual and Group Dynamics in Purchasing Activity

    Gao, Lei; Fan, Chao; Liu, Xue-Jiao


    As a major part of the daily operation in an enterprise, purchasing frequency is of constant change. Recent approaches on the human dynamics can provide some new insights into the economic behaviors of companies in the supply chain. This paper captures the attributes of creation times of purchasing orders to an individual vendor, as well as to all vendors, and further investigates whether they have some kind of dynamics by applying logarithmic binning to the construction of distribution plot. It's found that the former displays a power-law distribution with approximate exponent 2.0, while the latter is fitted by a mixture distribution with both power-law and exponential characteristics. Obviously, two distinctive characteristics are presented for the interval time distribution from the perspective of individual dynamics and group dynamics. Actually, this mixing feature can be attributed to the fitting deviations as they are negligible for individual dynamics, but those of different vendors are cumulated and t...

  11. v-Src causes delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone during cytokinesis failure

    Soeda, Shuhei [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan); Nakayama, Yuji, E-mail: [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan); Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414 (Japan); Honda, Takuya; Aoki, Azumi; Tamura, Naoki; Abe, Kohei; Fukumoto, Yasunori [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan); Yamaguchi, Naoto, E-mail: [Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675 (Japan)


    Src-family tyrosine kinases are aberrantly activated in cancers, and this activation is associated with malignant tumor progression. v-Src, encoded by the v-src transforming gene of the Rous sarcoma virus, is a mutant variant of the cellular proto-oncogene c-Src. Although investigations with temperature sensitive mutants of v-Src have shown that v-Src induces many oncogenic processes, the effects on cell division are unknown. Here, we show that v-Src inhibits cellular proliferation of HCT116, HeLa S3 and NIH3T3 cells. Flow cytometry analysis indicated that inducible expression of v-Src results in an accumulation of 4N cells. Time-lapse analysis revealed that binucleation is induced through the inhibition of cytokinesis, a final step of cell division. The localization of Mklp1, which is essential for cytokinesis, to the spindle midzone is inhibited in v-Src-expressing cells. Intriguingly, Aurora B, which regulates Mklp1 localization at the midzone, is delocalized from the spindle midzone and the midbody but not from the metaphase chromosomes upon v-Src expression. Mklp2, which is responsible for the relocation of Aurora B from the metaphase chromosomes to the spindle midzone, is also lost from the spindle midzone. These results suggest that v-Src inhibits cytokinesis through the delocalization of Mklp1 and Aurora B from the spindle midzone, resulting in binucleation. -- Highlights: • v-Src inhibits cell proliferation of HCT116, HeLa S3 and NIH3T3 cells. • v-Src induces binucleation together with cytokinesis failure. • v-Src causes delocalization of Mklp1, Aurora B and INCENP from the spindle midzone.

  12. A transmembrane inner nuclear membrane protein in the mitotic spindle

    Figueroa, Ricardo; Gudise, Santhosh; Larsson, Veronica; Hallberg, Einar


    We have recently characterized a novel transmembrane protein of the inner nuclear membrane of mammalian cells. The protein has two very interesting features. First, despite being an integral membrane protein it is able to concentrate in the membranes colocalizing with the mitotic spindle in metaphase and anaphase. Hence, the protein was named Samp1, Spindle associated membrane protein 1. Secondly, it displays a functional connection to centrosomes. This article discusses various aspects of Sa...

  13. A Novel Pathway that Coordinates Mitotic Exit with Spindle Position

    Nelson, Scott A.; Cooper, John A.


    In budding yeast, the spindle position checkpoint (SPC) delays mitotic exit until the mitotic spindle moves into the neck between the mother and bud. This checkpoint works by inhibiting the mitotic exit network (MEN), a signaling cascade initiated and controlled by Tem1, a small GTPase. Tem1 is regulated by a putative guanine exchange factor, Lte1, but the function and regulation of Lte1 remains poorly understood. Here, we identify novel components of the checkpoint that operate upstream of L...

  14. Enzyme activity below the dynamical transition at 220 K.

    Daniel, R M; Smith, J. C.; Ferrand, M; Héry, S; Dunn, R; Finney, J L


    Enzyme activity requires the activation of anharmonic motions, such as jumps between potential energy wells. However, in general, the forms and time scales of the functionally important anharmonic dynamics coupled to motion along the reaction coordinate remain to be determined. In particular, the question arises whether the temperature-dependent dynamical transition from harmonic to anharmonic motion in proteins, which has been observed experimentally and using molecular dynamics simulation, ...

  15. Selective detection of Escherichia coli DNA using fluorescent carbon spindles.

    Roy, Anurag; Chatterjee, Sabyasachi; Pramanik, Srikrishna; Devi, Parukuttyamma Sujatha; Suresh Kumar, Gopinatha


    We investigate the interaction of hydrophilic blue emitting carbon spindles with various deoxyribonucleic acids (DNA) having different base pair compositions, such as Herring testes (HT), calf thymus (CT), Escherichia coli (EC) and Micrococcus lysodeikticus (ML) DNA, to understand the mode of interaction. Interestingly, the fluorescent carbon spindles selectively interacted with E. coli DNA resulting in enhanced fluorescence of the former. Interaction of the same carbon with other DNAs exhibited insignificant changes in fluorescence. In addition, in the presence of EC DNA, the D band in the Raman spectrum attributed to the defect state completely disappeared, resulting in enhanced crystallinity. Microscopy images confirmed the wrapping of DNA on the carbon spindles leading to the assembly of spindles in the form of flowers. Dissociation of double-stranded DNA occurred upon interaction with carbon spindles, resulting in selective E. coli DNA interaction. The carbon spindles also exhibited a similar fluorescence enhancement upon treating with E. coli bacteria. These results confirm the possibility of E. coli detection in water and other liquid foods using such fluorescent carbon. PMID:27081680

  16. The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

    Veronica eKrenn


    Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

  17. Contribution of noncentrosomal microtubules to spindle assembly in Drosophila spermatocytes.

    Elena Rebollo


    Full Text Available Previous data suggested that anastral spindles, morphologically similar to those found in oocytes, can assemble in a centrosome-independent manner in cells that contain centrosomes. It is assumed that the microtubules that build these acentrosomal spindles originate over the chromatin. However, the actual processes of centrosome-independent microtubule nucleation, polymerisation, and sorting have not been documented in centrosome-containing cells. We have identified two experimental conditions in which centrosomes are kept close to the plasma membrane, away from the nuclear region, throughout meiosis I in Drosophila spermatocytes. Time-lapse confocal microscopy of these cells labelled with fluorescent chimeras reveals centrosome-independent microtubule nucleation, growth, and sorting into a bipolar spindle array over the nuclear region, away from the asters. The onset of noncentrosomal microtubule nucleation is significantly delayed with respect to nuclear envelope breakdown and coincides with the end of chromosome condensation. It takes place in foci that are close to the membranes that ensheath the nuclear region, not over the condensed chromosomes. Metaphase plates are formed in these spindles, and, in a fraction of them, some degree of polewards chromosome segregation takes place. In these cells that contain both membrane-bound asters and an anastral spindle, the orientation of the cytokinesis furrow correlates with the position of the asters and is independent of the orientation of the spindle. We conclude that the fenestrated nuclear envelope may significantly contribute to the normal process of spindle assembly in Drosophila spermatocytes. We also conclude that the anastral spindles that we have observed are not likely to provide a robust back-up able to ensure successful cell division. We propose that these anastral microtubule arrays could be a constitutive component of wild-type spindles, normally masked by the abundance of centrosome

  18. Microcystin-LR induces mitotic spindle assembly disorders in Vicia faba by protein phosphatase inhibition and not reactive oxygen species induction.

    Garda, Tamás; Kónya, Zoltán; Tándor, Ildikó; Beyer, Dániel; Vasas, Gábor; Erdődi, Ferenc; Vereb, György; Papp, Georgina; Riba, Milán; M-Hamvas, Márta; Máthé, Csaba


    We aimed to reveal the mechanisms of mitotic spindle anomalies induced by microcystin-LR (MCY-LR), a cyanobacterial toxin in Vicia faba, a well-known model in plant cell and molecular biology. MCY-LR inhibits type 1 and 2A phosphoserine/threonine specific protein phosphatases (PP1 and PP2A) and induces reactive oxygen species (ROS) formation. The cytoskeleton is one of the main targets of the cyanotoxin during cytopathogenesis. Histochemical-immunohistochemical and biochemical methods were used. A significant number of MCY-LR induced spindle alterations are described for the first time. Disrupted, multipolar spindles and missing kinetochore fibers were detected both in metaphase and anaphase cells. Additional polar microtubule (MT) bundles, hyperbundling of spindle MTs, monopolar spindles, C-S- shaped, additional and asymmetric spindles were detected in metaphase, while midplane kinetochore fibers were detected in anaphase cells only. Several spindle anomalies induced mitotic disorders, i.e. they occurred concomitantly with altered sister chromatid separation. Alterations were dependent on the MCY-LR dose and exposure time. Under long-term (2 and mainly 6 days') exposure they were detected in the concentration range of 0.1-20μgmL(-1) MCY-LR that inhibited PP1 and PP2A significantly without significant ROS induction. Elevated peroxidase/catalase activities indicated that MCY-LR treated V. faba plants showed efficient defense against oxidative stress. Thus, although the elevation of ROS is known to induce cytoskeletal aberrations in general, this study shows that long-term protein phosphatase inhibition is the primary cause of MCY-LR induced spindle disorders. PMID:27186862

  19. Dynamics and interactions of active rotors

    de Leoni, M. (Massimiliano); Liverpool, T. B.


    We consider a simple model of an internally driven self-rotating object; a rotor, confined to two dimensions by a thin film of low Reynolds number fluid. We undertake a detailed study of the hydrodynamic interactions between a pair of rotors and find that their effect on the resulting dynamics is a combination of fast and slow motions. We analyse the slow dynamics using an averaging procedure to take account of the fast degrees of freedom. Analytical results are compared with numerical simula...

  20. Topography-specific spindle frequency changes in Obstructive Sleep Apnea

    V Suzana


    Full Text Available Abstract Background Sleep spindles, as detected on scalp electroencephalography (EEG, are considered to be markers of thalamo-cortical network integrity. Since obstructive sleep apnea (OSA is a known cause of brain dysfunction, the aim of this study was to investigate sleep spindle frequency distribution in OSA. Seven non-OSA subjects and 21 patients with OSA (11 mild and 10 moderate were studied. A matching pursuit procedure was used for automatic detection of fast (≥13Hz and slow (Hz spindles obtained from 30min samples of NREM sleep stage 2 taken from initial, middle and final night thirds (sections I, II and III of frontal, central and parietal scalp regions. Results Compared to non-OSA subjects, Moderate OSA patients had higher central and parietal slow spindle percentage (SSP in all night sections studied, and higher frontal SSP in sections II and III. As the night progressed, there was a reduction in central and parietal SSP, while frontal SSP remained high. Frontal slow spindle percentage in night section III predicted OSA with good accuracy, with OSA likelihood increased by 12.1%for every SSP unit increase (OR 1.121, 95% CI 1.013 - 1.239, p=0.027. Conclusions These results are consistent with diffuse, predominantly frontal thalamo-cortical dysfunction during sleep in OSA, as more posterior brain regions appear to maintain some physiological spindle frequency modulation across the night. Displaying changes in an opposite direction to what is expected from the aging process itself, spindle frequency appears to be informative in OSA even with small sample sizes, and to represent a sensitive electrophysiological marker of brain dysfunction in OSA.

  1. Dynamic Activity-Related Incentives for Physical Activity.

    Schüler, Julia; Brunner, Sibylle


    The present studies adopted the theoretical framework of activity- and purpose-related incentives (Rheinberg, 2008) to explain the maintenance of physical activity. We hypothesized that activity-related incentives (e.g., “fun”) increase more than purpose-related incentives (e.g., “health”) between the initiation and maintenance phase of physical activity. Additionally, change in activity-related incentives was hypothesized to be a better predictor of maintenance of physical activity than chan...

  2. Dynamic activity-related incentives for physical activity


    The present studies adopted the theoretical framework of activity- and purpose-related incentives (Rheinberg, 2008) to explain the maintenance of physical activity. We hypothesized that activity-related incentives (e.g., “fun”) increase more than purpose-related incentives (e.g., “health”) between the initiation and maintenance phase of physical activity. Additionally, change in activity-related incentives was hypothesized to be a better predictor of maintenance of physical activity than chan...

  3. Spindle neurons of the human anterior cingulate cortex

    Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)


    The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

  4. Competing dynamic phases of active polymer networks

    Freedman, Simon; Banerjee, Shiladitya; Dinner, Aaron R.

    Recent experiments on in-vitro reconstituted assemblies of F-actin, myosin-II motors, and cross-linking proteins show that tuning local network properties can changes the fundamental biomechanical behavior of the system. For example, by varying cross-linker density and actin bundle rigidity, one can switch between contractile networks useful for reshaping cells, polarity sorted networks ideal for directed molecular transport, and frustrated networks with robust structural properties. To efficiently investigate the dynamic phases of actomyosin networks, we developed a coarse grained non-equilibrium molecular dynamics simulation of model semiflexible filaments, molecular motors, and cross-linkers with phenomenologically defined interactions. The simulation's accuracy was verified by benchmarking the mechanical properties of its individual components and collective behavior against experimental results at the molecular and network scales. By adjusting the model's parameters, we can reproduce the qualitative phases observed in experiment and predict the protein characteristics where phase crossovers could occur in collective network dynamics. Our model provides a framework for understanding cells' multiple uses of actomyosin networks and their applicability in materials research. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.


    Gong Jing; Sun Zhixin; Gu Qiang


    Aiming at the traditional passive deception models, this paper constructs a Decoy Platform based on Intelligent Agent (DPIA) to realize dynamic defense. The paper explores a new dynamic defense model based on active deception, introduces its architecture, and expatiates on communication methods and security guarantee in information transference. Simulation results show that the DPIA can attract hacker agility and activity, lead abnormal traffic into it, distribute a large number of attack data, and ensure real network security.

  6. MR imaging features of spindle cell lipoma

    Kirwadi, Anand; Abdul-Halim, Rehan; Highland, Adrian; Kotnis, Nikhil [Sheffield Teaching Hospitals NHS Trust, Radiology Department, Sheffield (United Kingdom); Fernando, Malee [Sheffield Teaching Hospitals NHS Trust, Histopathology Department, Sheffield (United Kingdom)


    To assess the MR imaging features of spindle cell lipomas (SCL) and to compare these appearances directly with the histopathological findings. A retrospective review of our soft tissue tumor database was performed. This yielded 1,327 histologically proven lipomas, of which 25 were confirmed as being SCLs. Fourteen of the 25 patients had MR examinations available for review and only these patients were included in our study. Lesions were assessed at MR examination for the degree of internal fat signal content with grade 0 representing 0 % fat signal and grade 4 100 % fat signal. The degree of fat suppression and contrast-enhancement pattern were also recorded. The excision specimens were independently reviewed by a consultant histopathologist. The histology specimens were assessed for the amount of internal fat and non-adipose tissue and graded using the same scale applied for the imaging. Where core needle biopsy (CNB) was performed, the CNB specimens were also examined for positive features of SCL. In our study, 93 % (13/14) of our patients were male and the average age was 58 years. 65 % (9/14) of the lesions presented in the upper back, shoulder, or neck. All lesions were subcutaneous. 35 % (5/14) of the SCLs demonstrated grade 3 (>75 %) or grade 4 (100 %) fat signal on MR examination. 35 % (5/14) of the lesions had grade 2 (25-75 %) fat signal and 29 % (4/14) of the lesions demonstrated grade 0 (0 %) or grade 1 (<25 %) fat signal. 43 % (6/14) of lesions demonstrated homogenous fat suppression, 28 % (4/14) showed focal areas of high internal signal, and 28 % (4/14) had diffuse internal high signal on fluid-sensitive fat-saturated sequences. 86 % (6/7) of the cases demonstrated septal/nodular enhancement. The diagnosis was evident on the CNB specimen in 100 % (9/9) cases. The histopathology fat content grade was in agreement with the imaging grade in 86 % (12/14) cases. The internal signal pattern of SCL can range broadly, with low fat content lesions seen almost

  7. Human Nek7-interactor RGS2 is required for mitotic spindle organization.

    de Souza, Edmarcia Elisa; Hehnly, Heidi; Perez, Arina Marina; Meirelles, Gabriela Vaz; Smetana, Juliana Helena Costa; Doxsey, Stephen; Kobarg, Jörg


    The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced γ-tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization. PMID:25664600

  8. Active cage model of glassy dynamics.

    Fodor, Étienne; Hayakawa, Hisao; Visco, Paolo; van Wijland, Frédéric


    We build up a phenomenological picture in terms of the effective dynamics of a tracer confined in a cage experiencing random hops to capture some characteristics of glassy systems. This minimal description exhibits scale invariance properties for the small-displacement distribution that echo experimental observations. We predict the existence of exponential tails as a crossover between two Gaussian regimes. Moreover, we demonstrate that the onset of glassy behavior is controlled only by two dimensionless numbers: the number of hops occurring during the relaxation of the particle within a local cage and the ratio of the hopping length to the cage size. PMID:27575182

  9. Spindle cell sarcoma of the penis. A case report

    A 75-year-old man, with a past history of radiation therapy for prostatic carcinoma ten years ago, was referred to our hospital with complaints of penile tumor. After pathological examination by core biopsy, the patient was treated by radical penectomy for a penile tumor. Pathological examinations demonstrated that the tumor was composed of pleomorphic spindle cells without any differentiation tendency and diagnosed as spindle cell sarcoma. Although the patient had a past history of radiation therapy for the prostate, the causal relation of development of penile sarcoma with the radiation therapy was uncertain because the main tumor was very near but outside of the irradiation field. The sarcoma rarely occurs in the penis, and this is the first report of penile spindle cell sarcoma, to our knowledge. (author)

  10. Activity of a social dynamics model

    Reia, Sandro M.; Neves, Ubiraci P. C.


    Axelrod's model was proposed to study interactions between agents and the formation of cultural domains. It presents a transition from a monocultural to a multicultural steady state which has been studied in the literature by evaluation of the relative size of the largest cluster. In this article, we propose new measurements based on the concept of activity per agent to study the Axelrod's model on the square lattice. We show that the variance of system activity can be used to indicate the critical points of the transition. Furthermore the frequency distribution of the system activity is able to show a coexistence of phases typical of a first order phase transition. Finally, we verify a power law dependence between cluster activity and cluster size for multicultural steady state configurations at the critical point.

  11. A dynamic model of active mode locking in gas lasers

    Mel' nikov, L.A.; Tatarkov, G.N. (Saratovskii Gosudarstvennyi Universitet, Saratov (USSR))


    A dynamic model is proposed for describing active mode locking in gas lasers with inhomogeneous broadening. Different dynamic modes of operation are examined as a function of the loss modulation depth. It is demonstrated that the destruction of mode locking is accompanied by the appearance of more complex dynamic states which can be either regular or chaotic. It is also shown that each individual pulse has a complex multihump structure resulting from the coherent character of the interaction between the electromagnetic field and the active medium. 14 refs.

  12. The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells.

    Conrad von Schubert

    Full Text Available The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

  13. Estimation of the in-plane vibrations of a rotating spindle, using out-of-plane laser vibrometry measurements

    Tatar, Kourosh; Gren, Per


    A method for estimating the in-plane vibrations of a rotating spindle using out-of-plane laser vibrometry measurements is described. This method enables the possibility to obtain the two orthogonal radial vibration components of a rotating spindle. The method uses the fact that the laser vibrometer signal is a total surface velocity of the measurement point in the laser direction. Measurements are conducted on a rotating milling machine spindle. The spindle is excited in a controlled manner by an active magnetic bearing and the response is measured by laser vibrometer in one of the two orthogonal directions and inductive displacement sensors in two orthogonal directions simultaneously. The work shows how the laser vibrometry crosstalk can be used for resolving the in-plane vibration component, that is the vibrations in the laser vibrometer cross direction. The result is compared to independent measurement signals from the displacement sensors. The measurement method can be used for vibration measurements on rotating parts, for example, where there is lack of space for orthogonal measurements.

  14. Imaging characteristics of spindle cell lipoma and its variants

    Khashper, Alla; Zheng, Jiamin [McGill University Health Centre, Department of Radiology, Montreal, QC (Canada); Nahal, Ayoub [McGill University Health Centre, Department of Pathology, Montreal, QC (Canada); Discepola, Federico [Jewish General Hospital, Department of Radiology, Montreal, QC (Canada)


    A spindle cell lipoma (SCL) is a relatively common tumor that can be challenging to the radiologist, pathologist, or surgeon to diagnose, particularly when internal fat content is scant or absent. Although these lesions may be found at various locations, the typical presentation for this lesion is a well-circumscribed and non-aggressive subcutaneous mass in the posterior neck presenting in a middle-aged to elderly man. In this article, the typical and atypical imaging characteristics of a spindle cell lipoma (SCL) will be reviewed. Knowledge of the common imaging and pathologic features of SCLs can help suggest the diagnosis and guide patient management. (orig.)

  15. Nonadiabatic scattering and transport at the spindle cusp

    When magnetohydrodynamics is used to describe plasma flow across a separatrix to open field lines, the transport is modeled by a diffusion equation with a sink for particles on the open lines. In that case, it is assumed that plasma is carried to and from the separatrix by diffusive processes. The purpose of this note is to discuss the nonadiabatic processes occurring at a spindle cusp to transfer plasma across a separatrix. After an ion is delivered to the vicinity of the separatrix by diffusion it enters the spindle cusp and will skip back and forth across the separatrix, producing a structured transport not seen with MHD

  16. Sensor-Based Activity Recognition with Dynamically Added Context

    Jiahui Wen


    Full Text Available An activity recognition system essentially processes raw sensor data and maps them into latent activity classes. Most of the previous systems are built with supervised learning techniques and pre-defined data sources, and result in static models. However, in realistic and dynamic environments, original data sources may fail and new data sources become available, a robust activity recognition system should be able to perform evolution automatically with dynamic sensor availability in dynamic environments. In this paper, we propose methods that automatically incorporate dynamically available data sources to adapt and refine the recognition system at run-time. The system is built upon ensemble classifiers which can automatically choose the features with the most discriminative power. Extensive experimental results with publicly available datasets demonstrate the effectiveness of our methods.

  17. A versatile multivariate image analysis pipeline reveals features of Xenopus extract spindles.

    Grenfell, Andrew W; Strzelecka, Magdalena; Crowder, Marina E; Helmke, Kara J; Schlaitz, Anne-Lore; Heald, Rebecca


    Imaging datasets are rich in quantitative information. However, few cell biologists possess the tools necessary to analyze them. Here, we present a large dataset ofXenopusextract spindle images together with an analysis pipeline designed to assess spindle morphology across a range of experimental conditions. Our analysis of different spindle types illustrates how kinetochore microtubules amplify spindle microtubule density. Extract mixing experiments reveal that some spindle features titrate, while others undergo switch-like transitions, and multivariate analysis shows the pleiotropic morphological effects of modulating the levels of TPX2, a key spindle assembly factor. We also apply our pipeline to analyze nuclear morphology in human cell culture, showing the general utility of the segmentation approach. Our analyses provide new insight into the diversity of spindle types and suggest areas for future study. The approaches outlined can be applied by other researchers studying spindle morphology and adapted with minimal modification to other experimental systems. PMID:27044897

  18. PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis.

    He, Jinxue; Zhang, Zhong; Ouyang, Meng; Yang, Fan; Hao, Hongbo; Lamb, Kristy L; Yang, Jingyi; Yin, Yuxin; Shen, Wen H


    Architectural integrity of the mitotic spindle is required for efficient chromosome congression and accurate chromosome segregation to ensure mitotic fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome stability. Here we report an essential role of PTEN in mitosis through regulation of the mitotic kinesin motor EG5 for proper spindle architecture and chromosome congression. PTEN depletion results in chromosome misalignment in metaphase, often leading to catastrophic mitotic failure. In addition, metaphase cells lacking PTEN exhibit defects of spindle geometry, manifested prominently by shorter spindles. PTEN is associated and co-localized with EG5 during mitosis. PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5 recruitment to the mitotic spindle apparatus, leading to spindle disorganization. These data demonstrate the functional interplay between PTEN and EG5 in controlling mitotic spindle structure and chromosome behaviour during mitosis. We propose that PTEN functions to equilibrate mitotic phosphorylation for proper spindle formation and faithful genomic transmission. PMID:27492783

  19. Active longitudes: Structure, dynamics, and rotation

    Ivanov, E. V.

    Greenwich data for 1879-2005 (cycles 12-23) are used to study the longitude distribution of sunspot group areas summed over a Carrington rotation s(CR) separately in the southern and northern hemispheres. The zones of active longitudes (AL) are identified, and their behaviour (location, shift, and intensity variations) is analyzed over the time interval under consideration. In particular, we have studied the active longitudes in two reference frames corresponding to the rotation periods T = 27.2753 and T = 27.00 days. The AL zones are shown to consist of a set of individual narrow sunspot formation zones rotating rigidly with the Carrington period T ˜ 27.2753 days. The lifetime of the sunspot formation zones exceeds significantly that of individual sunspots and may reach 15-20 rotations. Besides the rigidly rotating active longitudes we have revealed the active longitudes that migrate in the Carrington reference frame at different (greater and smaller than Carrington) angular velocities. Quasi-biennial oscillations (QBO) of the total sunspot areas in the northern and southern longitudinal sectors corresponding to AL zones are studied for the period 1879-2004 using the spectral and correlation analysis methods. The relationships between the antipodal, symmetric about the equator, and adjoining AL zones are analyzed.

  20. VMC-1000主轴箱模态分析及改进设计%Modal analysis and modification design of the VMC-1000 spindle box

    胡君君; 徐武彬; 张宏献; 唐满宾


    Natural and dynamic property of machine spindle box is one of the most important influencing factors to working accuracy,type VMC-1000 was studied.Based on finite element modal analysis,the imperfection of the machine spindle box was pointed out and a way was presented to improve the structure. In addition,the two different spindle boxes were analyzed with stiffness analysis to get the Maximum Deformation and Maximum stress of spindle box. According to the modal analysis and static analysis,the improved spindle box has high stiffness.%机床主轴箱的固有动态特性直接影响到机床的加工精度,以VMC-1000立式加工中心主轴箱为研究对象,应用有限元软件对其进行模态分析,提出了该主轴箱的薄弱环节.针对薄弱环节对箱体进行改进设计,通过比较分析,验证了改进的有效性.同时对两种结构刚度分析,得出主轴箱的最大变形量和最大应力,证实了改进的箱体结构具有较高的刚度.

  1. Fibrillarin redistributes to the spindle poles and partially colocalizes with NuMA during mitosis


    Fibrillarin, a major protein in the nucleolus, is known to redistribute during mitosis from the nucleolus to the cytosol, and is related to the dynamics of post-mitotic reassembly of the nucleolus. To better understand the dynamic behavior and the relationship with other cytoplasmic structures, we have now expressed fibrillarin-pDsRed1 fusion protein in HeLa cells. The results showed that a part of fibrillarin was associated with mitotic spindle poles in the mitotic cells. Nocodazole-induced microtubule depolymerization resulted in fibrillarin redistribution throughout the cytoplasm, and removal of nocodazole resulted in relocalization of fibrillarin at the polar region during the mitotic spindles reassembly. In a mitotic cell free system, fibrillarin was found in the center of taxol-induced microtubule asters. Moreover, fibrillarin was found to colocalize with the nuclear mitotic apparatus protein (NuMA) at the poles of mitotic cells. Therefore, it is postulated that the polar redistribution of fibrillarin is mediated by microtubules.

  2. The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindle disassembly

    Buvelot, Stéphanie; Tatsutani, Sean Y.; Vermaak, Danielle; Biggins, Sue


    Ipl1p is the budding yeast member of the Aurora family of protein kinases, critical regulators of genomic stability that are required for chromosome segregation, the spindle checkpoint, and cytokinesis. Using time-lapse microscopy, we found that Ipl1p also has a function in mitotic spindle disassembly that is separable from its previously identified roles. Ipl1–GFP localizes to kinetochores from G1 to metaphase, transfers to the spindle after metaphase, and accumulates at the spindle midzone ...

  3. Stiffness Identification of Spindle-Toolholder Joint Based on Finite Difference Technique and Residual Compensation Theory

    Zhifeng Liu; Xiaolei Song; Yongsheng Zhao; Ligang Cai; Hongsheng Guo; Jianchuan Ma


    The chatter vibration in high-speed machining mostly originates from the flexible connection of spindle and toolholder. Accurate identification of spindle-toolholder joint is crucial to predict machining stability of spindle system. This paper presents an enhanced stiffness identification method for the spindle-toolholder joint, in which the rotational degree of freedom (RDOF) is included. RDOF frequency response functions (FRFs) are formulated based on finite difference technique to construc...

  4. Activating and inhibiting connections in biological network dynamics

    Knight Rob


    Full Text Available Abstract Background Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos. Results Here we report that the balance between activating and inhibiting connections is important in determining whether network dynamics reach steady state or oscillate. We use a simple dynamical model of a network of interacting genes or proteins. Using the model, we study random networks, networks selected for robust dynamics, and examples of biological network topologies. The fraction of activating connections influences whether the network dynamics reach steady state or oscillate. Conclusion The activating fraction may predispose a network to oscillate or reach steady state, and neutral evolution or selection of this parameter may affect the behavior of biological networks. This principle may unify the dynamics of a wide range of cellular networks. Reviewers Reviewed by Sergei Maslov, Eugene Koonin, and Yu (Brandon Xia (nominated by Mark Gerstein. For the full reviews, please go to the Reviewers' comments section.

  5. 基于ANSYS的主轴轴承跨距的优化设计%The Optimization for the Bearings Span of Spindle Based on ANSYS

    汤本金; 孟凡富


    介绍了ANSYS优化设计的方法,并以主轴模态分析的一阶固有频率为目标函数,对CKH1450数控车铣中心主轴的轴承跨距进行了优化设计,从而提高了主轴系统的刚度,为主轴系统的热补偿提供了参考.%It introduces the FEM software ANSYS in optimization design application, builds the first set of vibration mode as the spindle dynamic object, takes CKH1450 CNC as an example to optimize the bearings span of spindle. This improves the spindle stiffness and provides a reference for thermal compensation design.

  6. Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2

    Hanisch, Anja; Silljé, Herman H W; Nigg, Erich A


    Chromosome segregation during mitosis requires chromosomes to undergo bipolar attachment on spindle microtubules (MTs) and subsequent silencing of the spindle checkpoint. Here, we describe the identification and characterisation of a novel spindle and kinetochore (KT)-associated complex that is requ

  7. Cell shape impacts on the positioning of the mitotic spindle with respect to the substratum.

    Lázaro-Diéguez, Francisco; Ispolatov, Iaroslav; Müsch, Anne


    All known mechanisms of mitotic spindle orientation rely on astral microtubules. We report that even in the absence of astral microtubules, metaphase spindles in MDCK and HeLa cells are not randomly positioned along their x-z dimension, but preferentially adopt shallow β angles between spindle pole axis and substratum. The nonrandom spindle positioning is due to constraints imposed by the cell cortex in flat cells that drive spindles that are longer and/or wider than the cell's height into a tilted, quasidiagonal x-z position. In rounder cells, which are taller, fewer cortical constraints make the x-z spindle position more random. Reestablishment of astral microtubule-mediated forces align the spindle poles with cortical cues parallel to the substratum in all cells. However, in flat cells, they frequently cause spindle deformations. Similar deformations are apparent when confined spindles rotate from tilted to parallel positions while MDCK cells progress from prometaphase to metaphase. The spindle disruptions cause the engagement of the spindle assembly checkpoint. We propose that cell rounding serves to maintain spindle integrity during its positioning. PMID:25657320

  8. Involvement of Spindles in Memory Consolidation Is Slow Wave Sleep-Specific

    Cox, Roy; Hofman, Winni F.; Talamini, Lucia M.


    Both sleep spindles and slow oscillations have been implicated in sleep-dependent memory consolidation. Whereas spindles occur during both light and deep sleep, slow oscillations are restricted to deep sleep, raising the possibility of greater consolidation-related spindle involvement during deep sleep. We assessed declarative memory retention…

  9. Hysteretic dynamics of active particles in a periodic orienting field.

    Romensky, Maksym; Scholz, Dimitri; Lobaskin, Vladimir


    Active motion of living organisms and artificial self-propelling particles has been an area of intense research at the interface of biology, chemistry and physics. Significant progress in understanding these phenomena has been related to the observation that dynamic self-organization in active systems has much in common with ordering in equilibrium condensed matter such as spontaneous magnetization in ferromagnets. The velocities of active particles may behave similar to magnetic dipoles and develop global alignment, although interactions between the individuals might be completely different. In this work, we show that the dynamics of active particles in external fields can also be described in a way that resembles equilibrium condensed matter. It follows simple general laws, which are independent of the microscopic details of the system. The dynamics is revealed through hysteresis of the mean velocity of active particles subjected to a periodic orienting field. The hysteresis is measured in computer simulations and experiments on unicellular organisms. We find that the ability of the particles to follow the field scales with the ratio of the field variation period to the particles' orientational relaxation time, which, in turn, is related to the particle self-propulsion power and the energy dissipation rate. The collective behaviour of the particles due to aligning interactions manifests itself at low frequencies via increased persistence of the swarm motion when compared with motion of an individual. By contrast, at high field frequencies, the active group fails to develop the alignment and tends to behave like a set of independent individuals even in the presence of interactions. We also report on asymptotic laws for the hysteretic dynamics of active particles, which resemble those in magnetic systems. The generality of the assumptions in the underlying model suggests that the observed laws might apply to a variety of dynamic phenomena from the motion of

  10. An anillin-Ect2 complex stabilizes central spindle microtubules at the cortex during cytokinesis.

    Paul Frenette

    Full Text Available Cytokinesis occurs due to the RhoA-dependent ingression of an actomyosin ring. During anaphase, the Rho GEF (guanine nucleotide exchange factor Ect2 is recruited to the central spindle via its interaction with MgcRacGAP/Cyk-4, and activates RhoA in the central plane of the cell. Ect2 also localizes to the cortex, where it has access to RhoA. The N-terminus of Ect2 binds to Cyk-4, and the C-terminus contains conserved DH (Dbl homologous and PH (Pleckstrin Homology domains with GEF activity. The PH domain is required for Ect2's cortical localization, but its molecular function is not known. In cultured human cells, we found that the PH domain interacts with anillin, a contractile ring protein that scaffolds actin and myosin and interacts with RhoA. The anillin-Ect2 interaction may require Ect2's association with lipids, since a novel mutation in the PH domain, which disrupts phospholipid association, weakens their interaction. An anillin-RacGAP50C (homologue of Cyk-4 complex was previously described in Drosophila, which may crosslink the central spindle to the cortex to stabilize the position of the contractile ring. Our data supports an analogous function for the anillin-Ect2 complex in human cells and one hypothesis is that this complex has functionally replaced the Drosophila anillin-RacGAP50C complex. Complexes between central spindle proteins and cortical proteins could regulate the position of the contractile ring by stabilizing microtubule-cortical interactions at the division plane to ensure the generation of active RhoA in a discrete zone.

  11. Complex Commingling: Nucleoporins and the Spindle Assembly Checkpoint

    Ikram Mossaid


    Full Text Available The segregation of the chromosomes during mitosis is an important process, in which the replicated DNA content is properly allocated into two daughter cells. To ensure their genomic integrity, cells present an essential surveillance mechanism known as the spindle assembly checkpoint (SAC, which monitors the bipolar attachment of the mitotic spindle to chromosomes to prevent errors that would result in chromosome mis-segregation and aneuploidy. Multiple components of the nuclear pore complex (NPC, a gigantic protein complex that forms a channel through the nuclear envelope to allow nucleocytoplasmic exchange of macromolecules, were shown to be critical for faithful cell division and implicated in the regulation of different steps of the mitotic process, including kinetochore and spindle assembly as well as the SAC. In this review, we will describe current knowledge about the interconnection between the NPC and the SAC in an evolutional perspective, which primarily relies on the two mitotic checkpoint regulators, Mad1 and Mad2. We will further discuss the role of NPC constituents, the nucleoporins, in kinetochore and spindle assembly and the formation of the mitotic checkpoint complex during mitosis and interphase.

  12. Screening tomato germplasm for resistance to potato spindle tuber viroid

    In recent years, several outbreaks of a potentially devastating viroid disease on tomato in North America have caused serious concerns to tomato growers and vegetable seed industry. Several closely related viroids in the genus Pospiviroid have been identified on tomato. Among them, Potato spindle t...

  13. Potato spindle tuber viroid: the simplicity paradox resolved?

    Taxonomy: Potato spindle tuber viroid (PSTVd) is the type species of the genus Posipiviroid, family Pospiviroidae. An absence of hammerhead ribozymes and the presence of a 'central conserved region' distinguish PSTVd and related viroids from members of a second viroid family, the Avsunviroidae. ...

  14. Experimental study on bearing preload optimum of machine tool spindle

    An experimental study is conducted to investigate the possibility and the effect of temperature rise and vibration level of bearing by adjusting axial preloads and radial loads in spindle bearing test rig. The shaft of the test rig is driven by a motorized high speed spindle at the range of 0∼20000 rpm. The axial preloads and radial loads on bearings are controlled by using hydraulic pressure which can be adjusted automatically. Temperature rise and radial vibration of test bearings are measured by thermocouples and Polytec portable laser vibrometer PDV100. Experiment shows that the temperature rise of bearings is nonlinear varying with the increase of radial loads, but temperature rise almost increases linearly with the increase of axial preload and rotating speed. In this paper, an alternate axial preload is used for bearings. When the rotating speed passes through the critical speed of the shaft, axial preload of bearings will have a remarkable effect. The low preload could reduce bearing vibration and temperature rise for bearings as well. At the others speed, the high preload could improve the vibration performance of high speed spindle and the bearing temperature was lower than that of the constant pressure preload spindle.

  15. A Balance between Nuclear and Cytoplasmic Volumes Controls Spindle Length

    Nováková, Lucia; Kovačovicová, Kristina; Dang-Nguyen, T.; Šodek, Martin; Škultéty, M.; Anger, Martin


    Roč. 11, č. 2 (2016), e0149535-e0149535. E-ISSN 1932-6203 R&D Projects: GA ČR GAP502/12/2201 Institutional support: RVO:67985904 Keywords : mitotoc spindle * size * cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  16. Improving the Dynamics of Suspension Bridges using Active Control Systems

    Thoft-Christensen, Palle

    Improving the dynamics of suspension bridge using active control is discussed in this paper. The main dynamic problem with long suspension bridges is the aeroelastic phenomenon called flutter. Flutter oscillations of a bridge girder is a stability problem and the oscillations are perpendicular to...... the direction of the wind and occur when the bridge is exposed to wind velocity above critical value called the flutter wind velocity Ucr....

  17. A spindle running on a five axes magnetic suspension based on conical bearings

    Carabelli, S.; Delprete, C.; Genta, G.; Moretto, I.


    The study and design of a small electric high-speed spindle based on two conical active magnetic bearings are described. The machine has been designed to simulate the rotor of a small turbo-compressor for the air conditioning unit of a small high performance aircraft. The two radial-axial bearings are controlled by a conventional five-axes decentralized compensator. The electromechanical components have been optimized for lightness and low cost. The unit here described constitutes an experimental rig for future studies in the field of magnetic suspension systems for high speed, small size rotating machinery.

  18. EB1 is required for spindle symmetry in mammalian mitosis.

    Anke Brüning-Richardson

    Full Text Available Most information about the roles of the adenomatous polyposis coli protein (APC and its binding partner EB1 in mitotic cells has come from siRNA studies. These suggest functions in chromosomal segregation and spindle positioning whose loss might contribute to tumourigenesis in cancers initiated by APC mutation. However, siRNA-based approaches have drawbacks associated with the time taken to achieve significant expression knockdown and the pleiotropic effects of EB1 and APC gene knockdown. Here we describe the effects of microinjecting APC- or EB1- specific monoclonal antibodies and a dominant-negative EB1 protein fragment into mammalian mitotic cells. The phenotypes observed were consistent with the roles proposed for EB1 and APC in chromosomal segregation in previous work. However, EB1 antibody injection also revealed two novel mitotic phenotypes, anaphase-specific cortical blebbing and asymmetric spindle pole movement. The daughters of microinjected cells displayed inequalities in microtubule content, with the greatest differences seen in the products of mitoses that showed the severest asymmetry in spindle pole movement. Daughters that inherited the least mobile pole contained the fewest microtubules, consistent with a role for EB1 in processes that promote equality of astral microtubule function at both poles in a spindle. We propose that these novel phenotypes represent APC-independent roles for EB1 in spindle pole function and the regulation of cortical contractility in the later stages of mitosis. Our work confirms that EB1 and APC have important mitotic roles, the loss of which could contribute to CIN in colorectal tumour cells.

  19. Protein-water dynamics in antifreeze protein III activity

    Xu, Yao; Bäumer, Alexander; Meister, Konrad; Bischak, Connor G.; DeVries, Arthur L.; Leitner, David M.; Havenith, Martina


    We combine Terahertz absorption spectroscopy (THz) and molecular dynamics (MD) simulations to investigate the underlying molecular mechanism for the antifreeze activity of one class of antifreeze protein, antifreeze protein type III (AFP-III) with a focus on the collective water hydrogen bond dynamics near the protein. After summarizing our previous work on AFPs, we present a new investigation of the effects of cosolutes on protein antifreeze activity by adding sodium citrate to the protein solution of AFP-III. Our results reveal that for AFP-III, unlike some other AFPs, the addition of the osmolyte sodium citrate does not affect the hydrogen bond dynamics at the protein surface significantly, as indicated by concentration dependent THz measurements. The present data, in combination with our previous THz measurements and molecular simulations, confirm that while long-range solvent perturbation is a necessary condition for the antifreeze activity of AFP-III, the local binding affinity determines the size of the hysteresis.

  20. Evolution and Dynamics of a Solar Active Prominence

    Magara, Tetsuya


    The life of a solar active prominence, one of the most remarkable objects on the Sun, is full of dynamics; after first appearing on the Sun the prominence continuously evolves with various internal motions and eventually produces a global eruption toward the interplane- tary space. Here we report that the whole life of an active prominence is successfully re- produced by performing as long-term a magnetohydrodynamic simulation of a magnetized prominence plasma as was ever done. The simulation reveals underlying dynamic processes that give rise to observed properties of an active prominence: invisible subsurface flows self- consistently produce the cancellation of magnetic flux observed at the photosphere, while observed and somewhat counterintuitive strong upflows are driven against gravity by en- hanced gas pressure gradient force along a magnetic field line locally standing vertical. The most highlighted dynamic event, transition into an eruptive phase, occurs as a natural con- sequence of the self-consiste...

  1. Dynamics of muscle activation during tonic-clonic seizures

    Conradsen, Isa; Moldovan, Mihai; Jennum, Poul;


    The purpose of our study was to elucidate the dynamics of muscle activation during generalised tonic-clonic seizures (GTCS). We recorded surface electromyography (EMG) from the deltoid muscle during 26 GTCS from 13 patients and compared it with GTCS-like events acted by 10 control subjects. GTCS...... consisted of a sequence of phases best described quantitatively by dynamics of the low frequency (LF) wavelet component (2-8Hz). Contrary to the traditional view, the tonic phase started with a gradual increase in muscle activity. A longer clonic phase was associated with a shorter onset of the tonic phase......) of exponentially increasing duration - features that could not be reproduced voluntarily. The last SP was longer in seizures with higher EMG peak frequency whereas the energy of the last clonus was higher in seizures with a short clonic phase. We found specific features of muscle activation dynamics...

  2. Escherichia coli activity characterization using a laser dynamic speckle technique

    Ramírez-Miquet, Evelio E; Contreras-Alarcón, Orestes R


    The results of applying a laser dynamic speckle technique to characterize bacterial activity are presented. The speckle activity was detected in two-compartment Petri dishes. One compartment was inoculated and the other one was left as a control blank. The speckled images were processed by the recently reported temporal difference method. Three inoculums of 0.3, 0.5, and 0.7 McFarland units of cell concentration were tested; each inoculum was tested twice for a total of six experiments. The dependences on time of the mean activity, the standard deviation of activity and other descriptors of the speckle pattern evolution were calculated for both the inoculated compartment and the blank. In conclusion the proposed dynamic speckle technique allows characterizing the activity of Escherichia coli bacteria in solid medium.

  3. Leiodermatolide, a novel marine natural product, has potent cytotoxic and antimitotic activity against cancer cells, appears to affect microtubule dynamics, and exhibits antitumor activity.

    Guzmán, Esther A; Xu, Qunli; Pitts, Tara P; Mitsuhashi, Kaoru Ogawa; Baker, Cheryl; Linley, Patricia A; Oestreicher, Judy; Tendyke, Karen; Winder, Priscilla L; Suh, Edward M; Wright, Amy E


    Pancreatic cancer, the fourth leading cause of cancer death in the United States, has a negative prognosis because metastasis occurs before symptoms manifest. Leiodermatolide, a polyketide macrolide with antimitotic activity isolated from a deep water sponge of the genus Leiodermatium, exhibits potent and selective cytotoxicity toward the pancreatic cancer cell lines AsPC-1, PANC-1, BxPC-3, and MIA PaCa-2, and potent cytotoxicity against skin, breast and colon cancer cell lines. Induction of apoptosis by leiodermatolide was confirmed in the AsPC-1, BxPC-3 and MIA PaCa-2 cells. Leiodermatolide induces cell cycle arrest but has no effects on in vitro polymerization or depolymerization of tubulin alone, while it enhances polymerization of tubulin containing microtubule associated proteins (MAPs). Observations through confocal microscopy show that leiodermatolide, at low concentrations, causes minimal effects on polymerization or depolymerization of the microtubule network in interphase cells, but disruption of spindle formation in mitotic cells. At higher concentrations, depolymerization of the microtubule network is observed. Visualization of the growing microtubule in HeLa cells expressing GFP-tagged plus end binding protein EB-1 showed that leiodermatolide stopped the polymerization of tubulin. These results suggest that leiodermatolide may affect tubulin dynamics without directly interacting with tubulin and hint at a unique mechanism of action. In a mouse model of metastatic pancreatic cancer, leiodermatolide exhibited significant tumor reduction when compared to gemcitabine and controls. The antitumor activities of leiodermatolide, as well as the proven utility of antimitotic compounds against cancer, make leiodermatolide an interesting compound with potential chemotherapeutic effects that may merit further research. PMID:27376928

  4. Protein Dynamics in Organic Media at Varying Water Activity Studied by Molecular Dynamics Simulation

    Wedberg, Nils Hejle Rasmus Ingemar; Abildskov, Jens; Peters, Günther H.J.


    In nonaqueous enzymology, control of enzyme hydration is commonly approached by fixing the thermodynamic water activity of the medium. In this work, we present a strategy for evaluating the water activity in molecular dynamics simulations of proteins in water/organic solvent mixtures. The method...... relies on determining the water content of the bulk phase and uses a combination of Kirkwood−Buff theory and free energy calculations to determine corresponding activity coefficients. We apply the method in a molecular dynamics study of Candida antarctica lipase B in pure water and the organic solvents...... methanol, tert-butyl alcohol, methyl tert-butyl ether, and hexane, each mixture at five different water activities. It is shown that similar water activity yields similar enzyme hydration in the different solvents. However, both solvent and water activity are shown to have profound effects on enzyme...

  5. Fission yeast cells undergo nuclear division in the absence of spindle microtubules.

    Stefania Castagnetti

    Full Text Available Mitosis in eukaryotic cells employs spindle microtubules to drive accurate chromosome segregation at cell division. Cells lacking spindle microtubules arrest in mitosis due to a spindle checkpoint that delays mitotic progression until all chromosomes have achieved stable bipolar attachment to spindle microtubules. In fission yeast, mitosis occurs within an intact nuclear membrane with the mitotic spindle elongating between the spindle pole bodies. We show here that in fission yeast interference with mitotic spindle formation delays mitosis only briefly and cells proceed to an unusual nuclear division process we term nuclear fission, during which cells perform some chromosome segregation and efficiently enter S-phase of the next cell cycle. Nuclear fission is blocked if spindle pole body maturation or sister chromatid separation cannot take place or if actin polymerization is inhibited. We suggest that this process exhibits vestiges of a primitive nuclear division process independent of spindle microtubules, possibly reflecting an evolutionary intermediate state between bacterial and Archeal chromosome segregation where the nucleoid divides without a spindle and a microtubule spindle-based eukaryotic mitosis.

  6. Forcing it on: Cytoskeletal dynamics during lymphocyte activation

    Upadhyaya, Arpita


    Formation of the immune synapse during lymphocyte activation involves cell spreading driven by large scale physical rearrangements of the actin cytoskeleton and the cell membrane. Several recent observations suggest that mechanical forces are important for efficient T cell activation. How forces arise from the dynamics of the cytoskeleton and the membrane during contact formation, and their effect on signaling activation is not well understood. We have imaged membrane topography, actin dynamics and the spatiotemporal localization of signaling clusters during the very early stages of spreading. Formation of signaling clusters was closely correlated with the movement and topography of the membrane in contact with the activating surface. Further, we observed membrane waves driven by actin polymerization originating at these signaling clusters. Actin-driven membrane protrusions likely play an important role in force generation at the immune synapse. In order to study cytoskeletal forces during T-cell activation, we studied cell spreading on elastic gels. We found that gel stiffness influences cell morphology, actin dynamics and receptor activation. Efforts to determine the quantitative relationships between cellular forces and signaling are underway. Our results suggest a role for cytoskeleton driven forces during signaling activation in lymphocytes.

  7. Deducing Shape of Anisotropic Particles in Solution from Light Scattering: Spindles and Nanorods

    Tsuper, Ilona; Terrano, Daniel; Streletzky, Kiril A.; Dement'eva, Olga V.; Semyonov, Sergey A.; Rudoy, Victor M.

    Depolarized Dynamic Light Scattering (DDLS) enables to measure rotational and translational diffusion of nanoparticles suspended in solution. The particle size, shape, diffusion, and interactions can then be inferred from the DDLS data using various models of diffusion. Incorporating the technique of DDLS to analyze the dimensions of easily imaged elongated particles, such as Iron (III) oxyhydroxide (FeOOH) Spindles and gold Nanorods, allows testing of the models for rotational and translational diffusion of elongated particles in solution. This, in turn, can help to better interpret DDLS data on hard-to-image anisotropic wet systems such as micelles, microgels, and protein complexes. This study focused on FeOOH Spindles and gold nanorod particles. The light scattering results on FeOOH analyzed using the basic model of non-interacting prolate ellipsoids yielded dimensions within 17% of the SEM measured dimensions. The dimensions of gold nanorod obtained from the straight cylinder model of DDLS data provided results within 25% of the sizes that were obtained from TEM. The nanorod DDLS data was also analyzed by a spherocylinder model.

  8. Inter-expert and intra-expert reliability in sleep spindle scoring

    Wendt, Sabrina Lyngbye; Welinder, Peter; Sørensen, Helge Bjarup Dissing;


    with higher reliability than the estimation of spindle duration. Reliability of sleep spindle scoring can be improved by using qualitative confidence scores, rather than a dichotomous yes/no scoring system. Conclusions We estimate that 2–3 experts are needed to build a spindle scoring dataset with...... ‘substantial’ reliability (κ: 0.61–0.8), and 4 or more experts are needed to build a dataset with ‘almost perfect’ reliability (κ: 0.81–1). Significance Spindle scoring is a critical part of sleep staging, and spindles are believed to play an important role in development, aging, and diseases of the nervous......Objectives To measure the inter-expert and intra-expert agreement in sleep spindle scoring, and to quantify how many experts are needed to build a reliable dataset of sleep spindle scorings. Methods The EEG dataset was comprised of 400 randomly selected 115 s segments of stage 2 sleep from 110...

  9. Developmental Changes in Sleep Spindle Characteristics and Sigma Power across Early Childhood.

    McClain, Ian J; Lustenberger, Caroline; Achermann, Peter; Lassonde, Jonathan M; Kurth, Salome; LeBourgeois, Monique K


    Sleep spindles, a prominent feature of the non-rapid eye movement (NREM) sleep electroencephalogram (EEG), are linked to cognitive abilities. Early childhood is a time of rapid cognitive and neurophysiological maturation; however, little is known about developmental changes in sleep spindles. In this study, we longitudinally examined trajectories of multiple sleep spindle characteristics (i.e., spindle duration, frequency, integrated spindle amplitude, and density) and power in the sigma frequency range (10-16 Hz) across ages 2, 3, and 5 years (n = 8; 3 males). At each time point, nocturnal sleep EEG was recorded in-home after 13-h of prior wakefulness. Spindle duration, integrated spindle amplitude, and sigma power increased with age across all EEG derivations (C3A2, C4A1, O2A1, and O1A2; all ps ontogenesis in early childhood and may help identify electrophysiological features related to healthy and aberrant brain maturation. PMID:27110405

  10. Controlled Activation of Protein Rotational Dynamics Using Smart Hydrogel Tethering

    Beech, Brenda M.; Xiong, Yijia; Boschek, Curt B.; Baird, Cheryl L.; Bigelow, Diana J.; Mcateer, Kathleen; Squier, Thomas C.


    Stimulus-responsive hydrogel materials that stabilize and control protein dynamics have the potential to enable a range of applications to take advantage of the inherent specificity and catalytic efficiencies of proteins. Here we describe the modular construction of a hydrogel using an engineered calmodulin (CaM) within a polyethylene glycol (PEG) matrix that involves the reversible tethering of proteins through an engineered CaM-binding sequence. For these measurements, maltose binding protein (MBP) was isotopically labeled with [13C] and [15N], permitting dynamic structural measurements using TROSY-HSQC NMR spectroscopy. Upon initial formation of hydrogels protein dynamics are suppressed, with concomitant increases in protein stability. Relaxation of the hydrogel matrix following transient heating results in the activation of protein dynamics and restoration of substrate-induced large-amplitude domain motions necessary for substrate binding.

  11. Dynamic Tracking of Web Activity Accessed by Users Using Cookies

    K.V.S. Jaharsh Samayan


    Full Text Available The motive of this study is to suggest a protocol which can be implemented to observe the activities of any node within a network whose contribution to the organization needs to be measured. Many associates working in any organization misuse the resources allocated to them and waste their working time in unproductive work which is of no use to the organization. In order to tackle this problem the dynamic approach in monitoring web pages accessed by user using cookies gives a very efficient way of tracking all the activities of the individual and store in cookies which are generated based on their recent web activity and display a statistical information of how the users web activity for the time period has been utilized for every IP-address in the network. In a ever challenging dynamic world monitoring the productivity of the associates in the organization plays an utmost important role.

  12. A comparison of two sleep spindle detection methods based on all night averages: individually adjusted versus fixed frequencies

    Péter Przemyslaw Ujma


    Full Text Available Sleep spindles are frequently studied for their relationship with state and trait cognitive variables, and they are thought to play an important role in sleep-related memory consolidation. Due to their frequent occurrence in NREM sleep, the detection of sleep spindles is only feasible using automatic algorithms, of which a large number is available. We compared subject averages of the spindle parameters computed by a fixed frequency (11-13 Hz for slow spindles, 13-15 Hz for fast spindles automatic detection algorithm and the individual adjustment method (IAM, which uses individual frequency bands for sleep spindle detection. Fast spindle duration and amplitude are strongly correlated in the two algorithms, but there is little overlap in fast spindle density and slow spindle parameters in general. The agreement between fixed and manually determined sleep spindle frequencies is limited, especially in case of slow spindles. This is the most likely reason for the poor agreement between the two detection methods in case of slow spindle parameters. Our results suggest that while various algorithms may reliably detect fast spindles, a more sophisticated algorithm primed to individual spindle frequencies is necessary for the detection of slow spindles as well as individual variations in the number of spindles in general.

  13. Active site modeling in copper azurin molecular dynamics simulations

    Rizzuti, B; Swart, M; Sportelli, L; Guzzi, R


    Active site modeling in molecular dynamics simulations is investigated for the reduced state of copper azurin. Five simulation runs (5 ns each) were performed at room temperature to study the consequences of a mixed electrostatic/constrained modeling for the coordination between the metal and the po

  14. Active synchronization between two different chaotic dynamical system

    Maheri, M. [Institute for Mathematical Research, 43400 UPM, Serdang, Selengor (Malaysia); Arifin, N. Md; Ismail, F. [Department of Mathematics, 43400 UPM, Serdang, Selengor (Malaysia)


    In this paper we investigate on the synchronization problem between two different chaotic dynamical system based on the Lyapunov stability theorem by using nonlinear control functions. Active control schemes are used for synchronization Liu system as drive and Rossler system as response. Numerical simulation by using Maple software are used to show effectiveness of the proposed schemes.

  15. Mechanisms regulating regional cerebral activation during dynamic handgrip in humans

    Williamson, James; Friedman, D B; Mitchell, J H; Secher, N H; Friberg, L


    type of afferent input required for this cerebral activation. The rCBF was measured at +5.0 and +9.0 cm above the orbitomeatal (OM) plane in 13 subjects during 1) rest; 2) dynamic left-hand contractions; 3) postcontraction ischemia (metaboreceptor afferents); and 4) biceps brachii tendon vibration...

  16. Are there sufficient diagnostic criteria for bronchial atypical carcinoid? A case report of bronchial pigmented spindle cell carcinoid with a review of the literature

    Piotr Lewitowicz


    Full Text Available Here we present a case of a 42-year-old female patient with pigmented spindle cell variant of bronchial carcinoid. The aim of this study was not only to record a rare variant of this tumour but also to highlight the differences in diagnostic criteria of gastrointestinal and bronchopulmonary-thymic neuroendocrine neoplasms. Ki-67 index is a discriminating factor in differential diagnosis between gastrointestinal neuroendocrine tumours (NETs and, only optionally, in bronchopulmonary-thymic tumours. Since diagnosis is currently based on mitotic activity, optionally Ki-67 index and tumour necrosis, a rare variant of NET, spindle cell carcinoids with cellular atypia could be potential pitfalls for diagnostic controversies or mistakes. Nevertheless, the presented case of typical carcinoid with spindle cell component and mild to moderate cellular atypia has been classified according current WHO criteria as a typical carcinoid.

  17. Radiation-induced spindle cell sarcoma: A rare case report

    Khan Mubeen


    Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

  18. Aerobic storage under dynamic conditions in activated sludge processes

    Majone, M.; Dircks, K.


    In activated sludge processes, several plant configurations (like plug-flow configuration of the aeration tanks, systems with selectors, contact-stabilization processes or SBR processes) impose a concentration gradient of the carbon sources to the biomass. As a consequence, the biomass grows under...... main reference to its relevance on population dynamics in the activated sludge. Possible conceptual approaches to storage modelling are also presented, including both structured and unstructured modelling. (C) 1999 IAWQ Published by Elsevier Science Ltd. All rights reserved....... mechanisms can also contribute to substrate removal, depending on the microbial composition and the previous "history" of the biomass. In this paper the type and the extent of this dynamic response is discussed by review of experimental studies on pure cultures, mixed cultures and activated sludges and with...

  19. Activation of the insular cortex during dynamic exercise in humans

    Williamson, James; Nobrega, A C; McColl, R;


    role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow...... during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling...... alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical...

  20. Dynamic phenomena and human activity in an artificial society

    Grabowski, A.; Kruszewska, N.; Kosiński, R. A.


    We study dynamic phenomena in a large social network of nearly 3×104 individuals who interact in the large virtual world of a massive multiplayer online role playing game. On the basis of a database received from the online game server, we examine the structure of the friendship network and human dynamics. To investigate the relation between networks of acquaintances in virtual and real worlds, we carried out a survey among the players. We show that, even though the virtual network did not develop as a growing graph of an underlying network of social acquaintances in the real world, it influences it. Furthermore we find very interesting scaling laws concerning human dynamics. Our research shows how long people are interested in a single task and how much time they devote to it. Surprisingly, exponent values in both cases are close to -1 . We calculate the activity of individuals, i.e., the relative time daily devoted to interactions with others in the artificial society. Our research shows that the distribution of activity is not uniform and is highly correlated with the degree of the node, and that such human activity has a significant influence on dynamic phenomena, e.g., epidemic spreading and rumor propagation, in complex networks. We find that spreading is accelerated (an epidemic) or decelerated (a rumor) as a result of superspreaders’ various behavior.

  1. Nonlinear dynamic interrelationships between real activity and stock returns

    Lanne, Markku; Nyberg, Henri

    We explore the differences between the causal and noncausal vector autoregressive (VAR) models in capturing the real activity-stock return-relationship. Unlike the conventional linear VAR model, the noncausal VAR model is capable of accommodating various nonlinear characteristics of the data. In...... quarterly U.S. data, we find strong evidence in favor of noncausality, and the best causal and noncausal VAR models imply quite different dynamics. In particular, the linear VAR model appears to underestimate the importance of the stock return shock for the real activity, and the real activity shock for the...

  2. Sleep spindle alterations in patients with Parkinson's disease

    Christensen, Julie Anja Engelhard; Nikolic, Miki; Warby, Simon C.;


    The aim of this study was to identify changes of sleep spindles (SS) in the EEG of patients with Parkinson's disease (PD). Five sleep experts manually identified SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched control subjects. Each SS was given a confidence score, and...... automatic detection of SS in patients with PD or other neurodegenerative disorders (NDDs)....

  3. CENP-32 is required to maintain centrosomal dominance in bipolar spindle assembly.

    Ohta, Shinya; Wood, Laura; Toramoto, Iyo; Yagyu, Ken-Ichi; Fukagawa, Tatsuo; Earnshaw, William C


    Centrosomes nucleate spindle formation, direct spindle pole positioning, and are important for proper chromosome segregation during mitosis in most animal cells. We previously reported that centromere protein 32 (CENP-32) is required for centrosome association with spindle poles during metaphase. In this study, we show that CENP-32 depletion seems to release centrosomes from bipolar spindles whose assembly they had previously initiated. Remarkably, the resulting anastral spindles function normally, aligning the chromosomes to a metaphase plate and entering anaphase without detectable interference from the free centrosomes, which appear to behave as free asters in these cells. The free asters, which contain reduced but significant levels of CDK5RAP2, show weak interactions with spindle microtubules but do not seem to make productive attachments to kinetochores. Thus CENP-32 appears to be required for centrosomes to integrate into a fully functional spindle that not only nucleates astral microtubules, but also is able to nucleate and bind to kinetochore and central spindle microtubules. Additional data suggest that NuMA tethers microtubules at the anastral spindle poles and that augmin is required for centrosome detachment after CENP-32 depletion, possibly due to an imbalance of forces within the spindle. PMID:25657325

  4. Automatic sleep spindle detection and genetic influence estimation using continuous wavelet transform

    Marek Adamczyk


    Full Text Available Mounting evidence for the role of sleep spindles for neuroplasticity led to an increased interest in these NREM sleep oscillations. It has been hypothesized that fast and slow spindles might play a different role in memory processing. Here we present a new sleep spindle detection algorithm utilizing a continuous wavelet transform and individual adjustment of slow and fast spindle frequency ranges. 18 nap recordings of 10 subjects were used for algorithm validation. Our method was compared with human scorer and commercially available SIESTA spindle detector. For the validation set, mean agreement between our detector and human scorer measured during sleep stage 2 using kappa coefficient was 0.45, whereas mean agreement between our detector and SIESTA algorithm was 0.62. Our algorithm was also applied to sleep-related memory consolidation data previously analyzed with SIESTA detector and confirmed previous findings of significant correlation between spindle density and declarative memory consolidation. Then, we applied our method to a study in monozygotic (MZ and dizygotic (DZ twins examining the heritability of slow and fast sleep spindle parameters. Our analysis revealed strong genetic influence of all slow spindle parameters, weaker genetic effect on fast spindles and no effects on fast spindle density and number during stage 2 sleep.

  5. Characterizing and modeling the dynamics of activity and popularity.

    Peng Zhang

    Full Text Available Social media, regarded as two-layer networks consisting of users and items, turn out to be the most important channels for access to massive information in the era of Web 2.0. The dynamics of human activity and item popularity is a crucial issue in social media networks. In this paper, by analyzing the growth of user activity and item popularity in four empirical social media networks, i.e., Amazon, Flickr, Delicious and Wikipedia, it is found that cross links between users and items are more likely to be created by active users and to be acquired by popular items, where user activity and item popularity are measured by the number of cross links associated with users and items. This indicates that users generally trace popular items, overall. However, it is found that the inactive users more severely trace popular items than the active users. Inspired by empirical analysis, we propose an evolving model for such networks, in which the evolution is driven only by two-step random walk. Numerical experiments verified that the model can qualitatively reproduce the distributions of user activity and item popularity observed in empirical networks. These results might shed light on the understandings of micro dynamics of activity and popularity in social media networks.

  6. Semi-active control of dynamically excited structures using active interaction control

    Zhang, Yunfeng


    This thesis presents a family of semi-active control algorithms termed Active Interaction Control (AIC) used for response control of dynamically excited structures. The AIC approach has been developed as a semi﷓active means of protecting building structures against large earthquakes. The AIC algorithms include the Active Interface Damping (AID), Optimal Connection Strategy (OCS), and newly developed Tuned Interaction Damping (TID) algorithms. All of the AIC algorithms are founded upon ...

  7. Dynamics of self-propelled nanomotors in chemically active media

    Thakur, Snigdha; Kapral, Raymond


    Synthetic chemically powered nanomotors often rely on the environment for their fuel supply. The propulsion properties of such motors can be altered if the environment in which they move is chemically active. The dynamical properties of sphere dimer motors, composed of linked catalytic and noncatalytic monomers, are investigated in active media. Chemical reactions occur at the catalytic monomer and the reactant or product of this reaction is involved in cubic autocatalytic or linear reactions that take place in the bulk phase environment. For these reactions, as the bulk phase reaction rates increase, the motor propulsion velocity decreases. For the cubic autocatalytic reaction, this net effect arises from a competition between a reduction of the nonequilibrium concentration gradient that leads to smaller velocity and the generation of fuel in the environment that tends to increase the motor propulsion. The role played by detailed balance in determining the form of the concentration gradient in the motor vicinity in the active medium is studied. Simulations are carried out using reactive multiparticle collision dynamics and compared with theoretical models to obtain further insight into sphere dimer dynamics in active media.

  8. Clathrin is spindle-associated but not essential for mitosis.

    Joana Borlido

    Full Text Available Clathrin is a multimeric protein involved in vesicle coat assembly. Recently clathrin distribution was reported to change during the cell cycle and was found to associate with the mitotic spindle. Here we test whether the recruitment of clathrin to the spindle is indicative of a critical functional contribution to mitosis.Previously a chicken pre-B lymphoma cell line (DKO-R was developed in which the endogenous clathrin heavy chain alleles were replaced with the human clathrin heavy chain under the control of a tetracycline-regulatable promoter. Receptor-mediated and fluid-phase endocytosis were significantly inhibited in this line following clathrin knockout, and we used this to explore the significance of clathrin heavy chain expression for cell cycle progression. We confirmed using confocal microscopy that clathrin colocalised with tubulin at mitotic spindles. Using a propidium iodide flow cytometric assay we found no statistical difference in the cell cycle distribution of the knockout cells versus the wild-type. Additionally, we showed that the ploidy and the recovery kinetics following cell cycle arrest with nocodazole were unchanged by repressing clathrin heavy chain expression.We conclude that the association of clathrin with the mitotic spindle and the contribution of clathrin to endocytosis are evolutionarily conserved. However we find that the contribution of clathrin to mitosis is less robust and dependent on cellular context. In other cell-lines silencing RNA has been used by others to knockdown clathrin expression resulting in an increase in the mitotic index of the cells. We show an effect on the G2/M phase population of clathrin knockdown in HEK293 cells but show that repressing clathrin expression in the DKO-R cell-line has no effect on the size of this population. Consequently this work highlights the need for a more detailed molecular understanding of the recruitment and function of clathrin at the spindle, since the

  9. Step by step approach to rare breast lesions containing spindle cells.

    Ünal, Betül; Erdoğan, Gülgün; Karaveli, Fatma Şeyda


    Differential diagnosis of spindle cell lesions of breast is challenging for certain reasons. The most important reason is the presence of cytological atypia and mitosis in all three conditions: reactive, benign, and malignant. Patients diagnosed with benign and malignant tumor/tumor-like lesions that had spindle cell components following the histopathological examination were included in the study. The patients' medical records were accessed to obtain the clinical history, follow-up notes, and radiological findings. Following histopathological, immunohistochemical, and clinical evaluations, the patients were diagnosed as follows: pseudoangiomatous stromal hyperplasia (PASH), bilateral desmoid-type fibromatosis (FM), adenomyoepithelioma (AME), myofibroblastoma (MFB), malignant phyllodes tumor (MF), high-grade AS, post-chemotherapy osteosarcoma (OS) + Paget's disease, and metaplastic carcinoma (MC). An algorithmic approach should be used in the diagnosis; cellular structure, presence and grade of atypia, growth pattern, mitotic activity, immunohistochemical staining, and clinical and radiological features should be evaluated together. Detection of some molecular changes can be useful in differential diagnosis. PMID:26558181

  10. Investigation of Flow Behavior around Corotating Blades in a Double-Spindle Lawn Mower Deck

    Chon W.


    Full Text Available When the airflow patterns inside a lawn mower deck are understood, the deck can be redesigned to be efficient and have an increased cutting ability. To learn more, a combination of computational and experimental studies was performed to investigate the effects of blade and housing designs on a flow pattern inside a 1.1m wide corotating double-spindle lawn mower deck with side discharge. For the experimental portion of the study, air velocities inside the deck were measured using a laser Doppler velocimetry (LDV system. A high-speed video camera was used to observe the flow pattern. Furthermore, noise levels were measured using a sound level meter. For the computational fluid dynamics (CFD work, several arbitrary radial sections of a two-dimensional blade were selected to study flow computations. A three-dimensional, full deck model was also developed for realistic flow analysis. The computational results were then compared with the experimental results.