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.

  11. A "Kanes's Dynamics" Model for the Active Rack Isolation System

    Hampton, R. David; Beech, Geoffrey


    Many microgravity space-science experiments require vibratory acceleration levels unachievable without active isolation. The Boeing Corporation's Active Rack Isolation System (ARIS) employs a novel combination of magnetic actuation and mechanical linkages, to address these isolation requirements on the International Space Station (ISS). ARIS provides isolation at the rack (international Standard Payload Rack, or ISPR) level. Effective model-based vibration isolation requires (1) an appropriate isolation device, (2) an adequate dynamic (i.e., mathematical) model of that isolator, and (3) a suitable, corresponding controller. ARIS provides the ISS response to the first requirement. This paper presents one response to the second, in a state-space framework intended to facilitate an optimal-controls approach to the third. The authors use "Kane's Dynamics" to develop an state-space, analytical (algebraic) set of linearized equations of motion for ARIS.

  12. Visual Experience Modulates Spatio-Temporal Dynamics of Circuit Activation

    Wang, Lang; Fontanini, Alfredo; Maffei, Arianna


    Persistent reduction in sensory drive in early development results in multiple plastic changes of different cortical synapses. How these experience-dependent modifications affect the spatio-temporal dynamics of signal propagation in neocortical circuits is poorly understood. Here we demonstrate that brief visual deprivation significantly affects the propagation of electrical signals in the primary visual cortex. The spatio-temporal spread of circuit activation upon direct stimulation of its i...

  13. Visual experience modulates spatio-temporal dynamics of circuit activation

    Arianna Maffei


    Persistent reduction in sensory drive in early development results in multiple plastic changes of different cortical synapses. How these experience-dependent modifications affect the spatio-temporal dynamics of signal propagation in neocortical circuits is poorly understood. Here we demonstrate that brief visual deprivation significantly affects the propagation of electrical signals in the primary visual cortex. The spatio-temporal spread of circuit activation upon direct stimulation of its i...

  14. Coarsening dynamics of binary liquids with active rotation.

    Sabrina, Syeda; Spellings, Matthew; Glotzer, Sharon C; Bishop, Kyle J M


    Active matter comprised of many self-driven units can exhibit emergent collective behaviors such as pattern formation and phase separation in both biological (e.g., mussel beds) and synthetic (e.g., colloidal swimmers) systems. While these behaviors are increasingly well understood for ensembles of linearly self-propelled "particles", less is known about the collective behaviors of active rotating particles where energy input at the particle level gives rise to rotational particle motion. A recent simulation study revealed that active rotation can induce phase separation in mixtures of counter-rotating particles in 2D. In contrast to that of linearly self-propelled particles, the phase separation of counter-rotating fluids is accompanied by steady convective flows that originate at the fluid-fluid interface. Here, we investigate the influence of these flows on the coarsening dynamics of actively rotating binary liquids using a phenomenological, hydrodynamic model that combines a Cahn-Hilliard equation for the fluid composition with a Navier-Stokes equation for the fluid velocity. The effect of active rotation is introduced though an additional force within the Navier-Stokes equations that arises due to gradients in the concentrations of clockwise and counter-clockwise rotating particles. Depending on the strength of active rotation and that of frictional interactions with the stationary surroundings, we observe and explain new dynamical behaviors such as "active coarsening" via self-generated flows as well as the emergence of self-propelled "vortex doublets". We confirm that many of the qualitative behaviors identified by the continuum model can also be found in discrete, particle-based simulations of actively rotating liquids. Our results highlight further opportunities for achieving complex dissipative structures in active materials subject to distributed actuation. PMID:26345231


    高云芳; 樊小力


    Objective In drugs for invigorating blood circulation, to find a herb that can stimulate afferent discharge of muscle spindle. Methods A single muscle spindle was isolated from sartorial muscle of toad. Using air-gap technique, afferent discharge of the muscle spindle was recorded. Effects of Angelica Sinensis, Salvia Miltiorrhiza, and Safflower on afferent discharge of the muscle spindle were observed. Results Angelica Sinensis could distinctly increase afferent discharge frequency of the muscle spindle, and this increase was dose-dependent. But Salvia Miltiorrhiza and Safflower had no this excitatory effect. Conclusion It is known that Angelica Sinensis can invigorate blood circulation, and we have found its excitatory effect on muscle spindle which makes it possible to serve people with muscle atrophy if more evidences from clinical experiments are available.

  16. A Kinesin Mutant with an Atypical Bipolar Spindle Undergoes Normal Mitosis

    Marcus, A. I.; Li, W.; Ma, H; Cyr, R. J.


    Motor proteins have been implicated in various aspects of mitosis, including spindle assembly and chromosome segregation. Here, we show that acentrosomal Arabidopsis cells that are mutant for the kinesin, ATK1, lack microtubule accumulation at the predicted spindle poles during prophase and have reduced spindle bipolarity during prometaphase. Nonetheless, all abnormalities are rectified by anaphase and chromosome segregation appears normal. We conclude that ATK1 is required for normal microtu...

  17. Mitotic Spindle Positioning in Saccharomyces cerevisiae Is Accomplished by Antagonistically Acting Microtubule Motor Proteins

    Cottingham, Frank R.; Hoyt, M. Andrew


    Proper positioning of the mitotic spindle is often essential for cell division and differentiation processes. The asymmetric cell division characteristic of budding yeast, Saccharomyces cerevisiae, requires that the spindle be positioned at the mother–bud neck and oriented along the mother–bud axis. The single dynein motor encoded by the S. cerevisiae genome performs an important but nonessential spindle-positioning role. We demonstrate that kinesin-related Kip3p makes a major contribution to...

  18. The role of muscle spindles in the development of the monosynaptic stretch reflex

    Wang, Zhi; Li, LingYing; Frank, Eric


    Muscle sensory axons induce the development of specialized intrafusal muscle fibers in muscle spindles during development, but the role that the intrafusal fibers may play in the development of the central projections of these Ia sensory axons is unclear. In the present study, we assessed the influence of intrafusal fibers in muscle spindles on the formation of monosynaptic connections between Ia (muscle spindle) sensory axons and motoneurons (MNs) using two transgenic strains of mice. Deleti...

  19. Asymmetric division of cyst stem cells in Drosophila testis is ensured by anaphase spindle repositioning

    Cheng, Jun; Tiyaboonchai, Amita; Yamashita, Yukiko M.; Hunt, Alan J.


    Many stem cells divide asymmetrically to balance self-renewal and differentiation. In Drosophila testes, two stem cell populations, germline stem cells (GSCs) and somatic cyst stem cells (CySCs), cohere and regulate one another. Here, we report that CySCs divide asymmetrically through repositioning the mitotic spindle around anaphase. CySC spindle repositioning requires functional centrosomes, Dynein and the actin-membrane linker Moesin. Anaphase spindle repositioning is required to achieve h...

  20. Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint.

    Sagar P Mahale

    Full Text Available The multi-functional molecular motor cytoplasmic dynein performs diverse essential roles during mitosis. The mechanistic importance of the dynein Light Intermediate Chain homologs, LIC1 and LIC2 is unappreciated, especially in the context of mitosis. LIC1 and LIC2 are believed to exist in distinct cytoplasmic dynein complexes as obligate subunits. LIC1 had earlier been reported to be required for metaphase to anaphase progression by inactivating the kinetochore-microtubule attachment-sensing arm of the spindle assembly checkpoint (SAC. However, the functional importance of LIC2 during mitosis remains elusive. Here we report prominent novel roles for the LIC2 subunit of cytoplasmic dynein in regulating the spindle assembly checkpoint. LIC2 depletion in mammalian cells led to prolonged metaphase arrest in the presence of an active SAC and also to stretched kinetochores, thus implicating it in SAC inactivation. Quantitative fluorescence microscopy of SAC components revealed accumulation of both attachment- and tension-sensing checkpoint proteins at metaphase kinetochores upon LIC2 depletion. These observations support a stronger and more diverse role in checkpoint inactivation for LIC2 in comparison to its close homolog LIC1. Our study uncovers a novel functional hierarchy during mitotic checkpoint inactivation between the closely related but homologous LIC subunits of cytoplasmic dynein. These subtle functional distinctions between dynein subpopulations could be exploited to study specific aspects of the spindle assembly checkpoint, which is a key mediator of fidelity in eukaryotic cell division.

  1. Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint

    Mahale, Sagar P.; Sharma, Amit; Mylavarapu, Sivaram V. S.


    The multi-functional molecular motor cytoplasmic dynein performs diverse essential roles during mitosis. The mechanistic importance of the dynein Light Intermediate Chain homologs, LIC1 and LIC2 is unappreciated, especially in the context of mitosis. LIC1 and LIC2 are believed to exist in distinct cytoplasmic dynein complexes as obligate subunits. LIC1 had earlier been reported to be required for metaphase to anaphase progression by inactivating the kinetochore-microtubule attachment-sensing arm of the spindle assembly checkpoint (SAC). However, the functional importance of LIC2 during mitosis remains elusive. Here we report prominent novel roles for the LIC2 subunit of cytoplasmic dynein in regulating the spindle assembly checkpoint. LIC2 depletion in mammalian cells led to prolonged metaphase arrest in the presence of an active SAC and also to stretched kinetochores, thus implicating it in SAC inactivation. Quantitative fluorescence microscopy of SAC components revealed accumulation of both attachment- and tension-sensing checkpoint proteins at metaphase kinetochores upon LIC2 depletion. These observations support a stronger and more diverse role in checkpoint inactivation for LIC2 in comparison to its close homolog LIC1. Our study uncovers a novel functional hierarchy during mitotic checkpoint inactivation between the closely related but homologous LIC subunits of cytoplasmic dynein. These subtle functional distinctions between dynein subpopulations could be exploited to study specific aspects of the spindle assembly checkpoint, which is a key mediator of fidelity in eukaryotic cell division. PMID:27441562

  2. Optimization of a High Speed Spinning Disk Spindle System for Minimum RRO , NRRO, and Lightweight by Using G.A.

    Y; H; Choi; S; T; Kim; K; C; Yoon; J; M; Kim; Y; J; Kang


    Law level of RRO(Repeatable Run Out), NRRO(Non Repe at able Run Out), and lightweight construction are a major trend in the high-speed HDD(Hard Disk Drive) sytem to reduce track misregestration and to achieve high track density, which lead to succeed in the market. However, it is not easy to r educe RRO, NRRO, and the weight of the spinning disk spindle system efficiently because lightweight construction and or bearing stiffness changes often yields a decrease in the static and dynamic stiffness of the ...

  3. Noninvasive three-dimensional live imaging methodology for the spindles at meiosis and mitosis

    Zheng, Jing-gao; Huo, Tiancheng; Tian, Ning; Chen, Tianyuan; Wang, Chengming; Zhang, Ning; Zhao, Fengying; Lu, Danyu; Chen, Dieyan; Ma, Wanyun; Sun, Jia-lin; Xue, Ping


    The spindle plays a crucial role in normal chromosome alignment and segregation during meiosis and mitosis. Studying spindles in living cells noninvasively is of great value in assisted reproduction technology (ART). Here, we present a novel spindle imaging methodology, full-field optical coherence tomography (FF-OCT). Without any dye labeling and fixation, we demonstrate the first successful application of FF-OCT to noninvasive three-dimensional (3-D) live imaging of the meiotic spindles within the mouse living oocytes at metaphase II as well as the mitotic spindles in the living zygotes at metaphase and telophase. By post-processing of the 3-D dataset obtained with FF-OCT, the important morphological and spatial parameters of the spindles, such as short and long axes, spatial localization, and the angle of meiotic spindle deviation from the first polar body in the oocyte were precisely measured with the spatial resolution of 0.7 μm. Our results reveal the potential of FF-OCT as an imaging tool capable of noninvasive 3-D live morphological analysis for spindles, which might be useful to ART related procedures and many other spindle related studies.

  4. Research on Control System of Spindle Drive for High Speed Spinning Machine



    Through analyzing the principle of spindle drive of winding mechanism for high speed spinning machine,the article not only describes a kind of mode of spindle drive for take-up motion on the basis of control method of constant velocity winding, but also introduces the design technique of software and hardware for the control system of mechatronics of spindle drive mode for take- up motion on the basis of constant velocity winding for high speed spinning machine with single-chip microcomputer. The mathematical model to describe the spindle rotating speed is established. It is an important technology for high speed spinning machine and provides a feasible application way.

  5. Dynamic properties of bright points in an active region

    Keys, Peter H; Jess, David B; Mackay, Duncan H; Keenan, Francis P


    Context. Bright points (BPs) are small-scale, magnetic features ubiquitous across the solar surface. Previously, we have observed and noted their properties for quiet Sun regions. Here, we determine the dynamic properties of BPs using simultaneous quiet Sun and active region data. Methods. High spatial and temporal resolution G-band observations of active region AR11372 were obtained with the Rapid Oscillations in the Solar Atmosphere instrument at the Dunn Solar Telescope. Three subfields of varying polarity and magnetic flux density were selected with the aid of magnetograms obtained from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory. Bright points within these subfields were subsequently tracked and analysed. Results. It is found that BPs within active regions display attenuated velocity distributions with an average horizontal velocity of ~0.6 km/s, compared to the quiet region which had an average velocity of 0.9 km/s. Active region BPs are also ~21% larger than quiet regio...

  6. Nonlinear Dynamical Analysis on Four Semi-Active Dynamic Vibration Absorbers with Time Delay

    Yongjun Shen


    Full Text Available In this paper four semi-active dynamic vibration absorbers (DVAs are analytically studied, where the time delay induced by measurement and execution in control procedure is included in the system. The first-order approximate analytical solutions of the four semi-active DVAs are established by the averaging method, based on the illustrated phase difference of the motion parameters. The comparisons between the analytical and the numerical solutions are carried out, which verify the correctness and satisfactory precision of the approximate analytical solutions. Then the effects of the time delay on the dynamical responses are analyzed, and it is found that the stability conditions for the steady-state responses of the primary systems are all periodic functions of time delay, with the same period as the excitation one. At last the effects of time delay on control performance are discussed.

  7. Multi-dimensional dynamics of human electromagnetic brain activity

    Tetsuo eKida


    Full Text Available Magnetoencephalography (MEG and electroencephalography (EEG are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency, which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory analyses applied to MEG/EEG signals. We briefly describe recent developments in source reconstruction algorithms essential for source-space connectivity and network analyses. Furthermore, we discuss a relatively novel approach used in MEG/EEG studies to examine the complex dynamics represented by human brain activity. The correct and effective use of these neuronal metrics provides a new insight into the multi-dimensional dynamics of the neural representations of various functions in the complex human brain.

  8. Visual experience modulates spatio-temporal dynamics of circuit activation

    Arianna Maffei


    Full Text Available Persistent reduction in sensory drive in early development results in multiple plastic changes of different cortical synapses. How these experience-dependent modifications affect the spatio-temporal dynamics of signal propagation in neocortical circuits is poorly understood. Here we demonstrate that brief visual deprivation significantly affects the propagation of electrical signals in the primary visual cortex. The spatio-temporal spread of circuit activation upon direct stimulation of its input layer (Layer 4 is reduced, as is the activation of Layer 2/3 – the main recipient of the output from Layer 4. Our data suggest that the decrease in spatio-temporal activation of L2/3 depends on reduced L4 output, and is not intrinsically generated within L2/3. The data shown here suggest that changes in the synaptic components of the visual cortical circuit result not only in alteration of local integration of excitatory and inhibitory inputs, but also in a significant decrease in overall circuit activation. Furthermore, our data indicate a differential effect of visual deprivation on L4 and L2/3, suggesting that while feedforward activation of L2/3 is reduced, its activation by long range, within layer inputs is unaltered. Thus, brief visual deprivation induces experience-dependent circuit re-organization by modulating not only circuit excitability, but also the spatio-temporal patterns of cortical activation within and between layers.

  9. A 5-DOF Model for Aeroengine Spindle Dual-rotor System Analysis

    HU Qinghua; DENG Sier; TENG Hongfei


    This paper develops a five degrees of freedom (5-DOF) model for aeroengine spindle dual-rotor system dynamic analysis.In this system, the dual rotors are supported on two angular contact ball bearings and two deep groove ball bearings, one of the latter-mentioned bearings works as the inter-shaft bearing.Driven by respective motors, the dual rotors have different co-rotating speeds.The proposed model mathematically formulates the nonlinear displacements, elastic deflections and contact forces of beatings with consideration of 5-DOF and coupling of dual rotors.The nonlinear equations of motions of dual rotors with 5-DOF are solved using Runge-Kutta-Fehlberg algorithm.In order to investigate the effect of the introduced 5-DOF and nonlinear dynamic bearing model, we compare the proposed model with two models: the 3-DOF model of this system only considering three translational degrees of freedom (Gupta, 1993, rotational freedom is neglected); the 5-DOF model where the deep groove ball bearings are simplified as linear elastic spring (Guskov, 2007).The simulation results verify Gupta's prediction (1993) and show that the rotational freedom of rotors and nonlinear dynamic model of bearings have great effect on the system dynamic simulation.The quantitative results are given as well.

  10. Dynamical criticality in the collective activity of a neural population

    Mora, Thierry

    The past decade has seen a wealth of physiological data suggesting that neural networks may behave like critical branching processes. Concurrently, the collective activity of neurons has been studied using explicit mappings to classic statistical mechanics models such as disordered Ising models, allowing for the study of their thermodynamics, but these efforts have ignored the dynamical nature of neural activity. I will show how to reconcile these two approaches by learning effective statistical mechanics models of the full history of the collective activity of a neuron population directly from physiological data, treating time as an additional dimension. Applying this technique to multi-electrode recordings from retinal ganglion cells, and studying the thermodynamics of the inferred model, reveals a peak in specific heat reminiscent of a second-order phase transition.

  11. Superfluid-like dynamics in active vortex fluids

    Slomka, Jonasz; Dunkel, Jorn

    Active biological fluids exhibit rich non-equilibrium dynamics and share striking similarities with quantum fluids, from vortex formation and magnetic ordering to superfluid-like behavior. Building on universality ideas, we have recently proposed a generalization of the Navier-Stokes equations that captures qualitatively the active bulk flow structures observed in bacterial suspensions. Here, we present new numerical simulations that explicitly account for boundary and shear effects. The theory successfully reproduces recent experimental observations of bacterial suspensions, including a superfluid-like regime of nearly vanishing shear viscosity. Our simulations further predict a geometry-induced 'quantization' of viscosity and the existence of excited states capable of performing mechanical work. It is plausible that these results generalize to a broad a class of fluids that are subject to an active scale selection mechanism.

  12. CARER: Efficient Dynamic Sensing for Continuous Activity Monitoring

    Au, Lawrence K.; Bui, Alex A.T.; Batalin, Maxim A.; Xu, Xiaoyu; Kaiser, William J.


    Advancement in wireless health sensor systems has triggered rapidly expanding research in continuous activity monitoring for chronic disease management or promotion and assessment of physical rehabilitation. Wireless motion sensing is increasingly important in treatments where remote collection of sensor measurements can provide an in-field objective evaluation of physical activity patterns. The well-known challenge of limited operating lifetime of energy-constrained wireless health sensor systems continues to present a primary limitation for these applications. This paper introduces CARER, a software system that supports a novel algorithm that exploits knowledge of context and dynamically schedules sensor measurement episodes within an energy consumption budget while ensuring classification accuracy. The sensor selection algorithm in the CARER system is based on Partially Observable Markov Decision Process (POMDP). The parameters for the POMDP algorithm can be obtained through standard maximum likelihood estimation. Sensor data are also collected from multiple locations of the subjects body, providing estimation of an individual's daily activity patterns. PMID:22254783

  13. Stochastic dynamics of active swimmers in linear flows

    Sandoval, Mario; Subramanian, Ganesh; Lauga, Eric


    Most classical work on the hydrodynamics of low-Reynolds-number swimming addresses deterministic locomotion in quiescent environments. Thermal fluctuations in fluids are known to lead to a Brownian loss of the swimming direction. As most cells or synthetic swimmers are immersed in external flows, we consider theoretically in this paper the stochastic dynamics of a model active particle (a self-propelled sphere) in a steady general linear flow. The stochasticity arises both from translational diffusion in physical space, and from a combination of rotary diffusion and run-and-tumble dynamics in orientation space. We begin by deriving a general formulation for all components of the long-time mean square displacement tensor for a swimmer with a time-dependent swimming velocity and whose orientation decorrelates due to rotary diffusion alone. This general framework is applied to obtain the convectively enhanced mean-squared displacements of a steadily-swimming particle in three canonical linear flows (extension, s...

  14. Sensitivity evaluation of dynamic speckle activity measurements using clustering methods

    We evaluate and compare the use of competitive neural networks, self-organizing maps, the expectation-maximization algorithm, K-means, and fuzzy C-means techniques as partitional clustering methods, when the sensitivity of the activity measurement of dynamic speckle images needs to be improved. The temporal history of the acquired intensity generated by each pixel is analyzed in a wavelet decomposition framework, and it is shown that the mean energy of its corresponding wavelet coefficients provides a suited feature space for clustering purposes. The sensitivity obtained by using the evaluated clustering techniques is also compared with the well-known methods of Konishi-Fujii, weighted generalized differences, and wavelet entropy. The performance of the partitional clustering approach is evaluated using simulated dynamic speckle patterns and also experimental data.

  15. Spindle cell hemangioma: Unusual presentation of an uncommon tumor

    Olalere Omoyosola Gbolahan


    Full Text Available Spindle cell hemangioma (SCH is an uncommon tumor that usually presents as subcutaneous or deep dermal nodule affecting the extremities and is typically <2 cm in size. A few cases have been reported in the head and neck region. To the best of the authors' knowledge, there are no previous reports of SCH occurring in the orbit in the English literature. We, therefore, report the case of a large SCH involving the right orbit of a healthy 9-year-old Nigerian girl.

  16. An undergraduate laboratory activity on molecular dynamics simulations.

    Spitznagel, Benjamin; Pritchett, Paige R; Messina, Troy C; Goadrich, Mark; Rodriguez, Juan


    Vision and Change [AAAS, 2011] outlines a blueprint for modernizing biology education by addressing conceptual understanding of key concepts, such as the relationship between structure and function. The document also highlights skills necessary for student success in 21st century Biology, such as the use of modeling and simulation. Here we describe a laboratory activity that allows students to investigate the dynamic nature of protein structure and function through the use of a modeling technique known as molecular dynamics (MD). The activity takes place over two lab periods that are 3 hr each. The first lab period unpacks the basic approach behind MD simulations, beginning with the kinematic equations that all bioscience students learn in an introductory physics course. During this period students are taught rudimentary programming skills in Python while guided through simple modeling exercises that lead up to the simulation of the motion of a single atom. In the second lab period students extend concepts learned in the first period to develop skills in the use of expert MD software. Here students simulate and analyze changes in protein conformation resulting from temperature change, solvation, and phosphorylation. The article will describe how these activities can be carried out using free software packages, including Abalone and VMD/NAMD. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:130-139, 2016. PMID:26751047

  17. Evolution of Parallel Spindles Like genes in plants and highlight of unique domain architecture#

    Consiglio Federica M


    Full Text Available Abstract Background Polyploidy has long been recognized as playing an important role in plant evolution. In flowering plants, the major route of polyploidization is suggested to be sexual through gametes with somatic chromosome number (2n. Parallel Spindle1 gene in Arabidopsis thaliana (AtPS1 was recently demonstrated to control spindle orientation in the 2nd division of meiosis and, when mutated, to induce 2n pollen. Interestingly, AtPS1 encodes a protein with a FHA domain and PINc domain putatively involved in RNA decay (i.e. Nonsense Mediated mRNA Decay. In potato, 2n pollen depending on parallel spindles was described long time ago but the responsible gene has never been isolated. The knowledge derived from AtPS1 as well as the availability of genome sequences makes it possible to isolate potato PSLike (PSL and to highlight the evolution of PSL family in plants. Results Our work leading to the first characterization of PSLs in potato showed a greater PSL complexity in this species respect to Arabidopsis thaliana. Indeed, a genomic PSL locus and seven cDNAs affected by alternative splicing have been cloned. In addition, the occurrence of at least two other PSL loci in potato was suggested by the sequence comparison of alternatively spliced transcripts. Phylogenetic analysis on 20 Viridaeplantae showed the wide distribution of PSLs throughout the species and the occurrence of multiple copies only in potato and soybean. The analysis of PSLFHA and PSLPINc domains evidenced that, in terms of secondary structure, a major degree of variability occurred in PINc domain respect to FHA. In terms of specific active sites, both domains showed diversification among plant species that could be related to a functional diversification among PSL genes. In addition, some specific active sites were strongly conserved among plants as supported by sequence alignment and by evidence of negative selection evaluated as difference between non-synonymous and

  18. Characterizing and Modeling the Dynamics of Activity and Popularity

    Zhang, Peng; Gao, Liang; Fan, Ying; Di, Zengru


    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 much 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...

  19. Atmosphere dynamics of the active region NOAA 11024

    Kondrashova, N N; Chornogor, S N; Khomenko, E V; 10.1007/s11207-012-0212-5


    We present results of the study of chromospheric and photospheric line-of-sight velocity fields in the young active region NOAA 11024. Multi-layer, multi-wavelength observational data were used for the analysis of the emerging flux in this active region. Spectropolarimetric observations were carried out with the telescope THEMIS on Tenerife (Canary Islands) on 4 July 2009. In addition, space-borne data from SOHO/MDI, STEREO and GOES were also considered. The combination of data from ground- and space-based telescopes allowed us to study the dynamics of the lower atmosphere of the active region with high spatial, spectral, and temporal resolutions. THEMIS spectra show strong temporal variations of the velocity in the chromosphere and photosphere for different activity features: two pores, active and quiet plage regions, and two surges. The range of variations of the chromospheric line-of-sight velocity at the heights of formation of the H-alpha core was extremely large. Both upward and downward motions were ob...




    Full Text Available ABSTRACT : Malignant tumors of vagina are rare accounting for 1 to 4 % of all genital malignancies. Rarest of rare is spindle cell sarcoma of vagina having a very poor prognosis. 47yrs old, regularly menstruating woman, completed f amily, presented with hard painful ulcerated swelling near the vaginal introitus and l ower vaginal wall of 4 months duration. On examination, 2x4cms sized ulcerated growth with exc avated base, covered with necrotic material, present in the left antero-lateral lower e nd of vagina, inner to hymenal ring which was tender, hard, indurated, infiltrating, fixed to bas e and did not bleed to touch. Another nodule of size 1x1cm tender, hard, fixed and necrotic was pres ent below the external urethral meatus. HPE revealed Amelanotic malignant melanoma of vagin a. Immunohistochemistry revealed Spindle cell sarcoma of vagina. Tumor board recommen ded neo-adjuvant chemotherapy and radiotherapy (CT + EBRT. Of the recommended 50Gy, s he completed 46Gy in 23days and 1 course of chemotherapy (VAC. On review after 9 mont hs, the lesion disappeared clinically and she was advised to complete the treatment. Inspite o f radio and chemotherapy secondaries to lungs and brain could not be prevented and the patien t expired 20 months after the final diagnosis

  1. Cenp-meta is required for sustained spindle checkpoint

    Thomas Rubin


    Full Text Available Cenp-E is a kinesin-like motor protein required for efficient end-on attachment of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus mitotic extracts results in the loss of mitotic arrest and massive chromosome missegregation, whereas its depletion in mammalian cells leads to chromosome segregation defects despite the presence of a functional spindle assembly checkpoint (SAC. Cenp-meta has previously been reported to be the Drosophila homolog of vertebrate Cenp-E. In this study, we show that cenp-metaΔ mutant neuroblasts arrest in mitosis when treated with colchicine. cenp-metaΔ mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that cenp-metaΔ mutant cells display a slow but continuous degradation of cyclin B, which eventually triggers the mitotic exit observed. Thus, our data provide evidence for a role of Cenp-meta in sustaining the SAC response.

  2. An Overview of the Spindle Assembly Checkpoint Status in Oral Cancer

    Teixeira, José Henrique; Silva, Patrícia Manuela; Reis, Rita Margarida; Moura, Inês Moranguinho; Marques, Sandra; Fonseca, Joana; Monteiro, Luís Silva; Bousbaa, Hassan


    Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20. PMID:24995269

  3. Lanthanide co-doped paramagnetic spindle-like mesocrystals for imaging and autophagy induction.

    Xu, Yun-Jun; Lin, Jun; Lu, Yang; Zhong, Sheng-Liang; Wang, Lei; Dong, Liang; Wu, Ya-Dong; Peng, Jun; Zhang, Li; Pan, Xiao-Feng; Zhou, Wei; Zhao, Yang; Wen, Long-Ping; Yu, Shu-Hong


    We synthesized two novel lanthanide doped spindle-like mesocrystals, YF3:Ce,Eu,Gd and YF3:Ce,Tb,Gd (abbreviated as YEG and YTG mesospindles, respectively). Both of them possess paramagnetic and fluorescent properties, and their excellent cyto-compatibility and low haemolysis are further confirmed. Therefore, they could act as dual mode contrast agents for magnetic resonance imaging (MRI) and fluorescence imaging. Furthermore, YEG and YTG mesospindles induce dose and time dependent autophagy by activating the PI3K signaling pathway. The autophagy induced by YEG and YTG mesocrystals is confirmed by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. This work is important to illustrate how rare-earth mesocrystals affect the autophagic pathway, indicating the potential of the YEG and YTG mesospindles in diagnosis and therapy. PMID:27346838

  4. Broken Detailed Balance of Filament Dynamics in Active Networks

    Gladrow, J.; Fakhri, N.; MacKintosh, F. C.; Schmidt, C. F.; Broedersz, C. P.


    Myosin motor proteins drive vigorous steady-state fluctuations in the actin cytoskeleton of cells. Endogenous embedded semiflexible filaments such as microtubules, or added filaments such as single-walled carbon nanotubes are used as novel tools to noninvasively track equilibrium and nonequilibrium fluctuations in such biopolymer networks. Here, we analytically calculate shape fluctuations of semiflexible probe filaments in a viscoelastic environment, driven out of equilibrium by motor activity. Transverse bending fluctuations of the probe filaments can be decomposed into dynamic normal modes. We find that these modes no longer evolve independently under nonequilibrium driving. This effective mode coupling results in nonzero circulatory currents in a conformational phase space, reflecting a violation of detailed balance. We present predictions for the characteristic frequencies associated with these currents and investigate how the temporal signatures of motor activity determine mode correlations, which we find to be consistent with recent experiments on microtubules embedded in cytoskeletal networks.

  5. Time scales and dynamical processes in activity driven networks

    Perra, Nicola; Goncalves, Bruno; Pastor-Satorras, Romualdo; Vespignani, Alessandro


    Network science has undergone explosive growth in the last ten years. This growth has been driven by the recent availability of huge digital databases, which has facilitated the analysis and construction of large-scale networks from real data and the identification of statistical regularities and structural principles common to many systems. Network modeling has played an essential role in this endeavor; however models are chiefly constructed by considering as relevant ingredients only the connectivity and statistical properties of the networks, while disregarding the actual agents' behavior. Here we address this challenge by measuring the agents' interaction activity in real-world networks and defining a minimal model capable of reproducing the intrinsically additive nature of connectivity patterns obtained from time-aggregated network representations. Additionally, we demonstrate that processes such as epidemic and information spreading in highly dynamical networks can be better characterized in terms of agent social activity than by connectivity based approaches

  6. Activity clocks: spreading dynamics on temporal networks of human contact

    Gauvin, Laetitia; Cattuto, Ciro; Barrat, Alain


    Dynamical processes on time-varying complex networks are key to un- derstanding and modeling a broad variety of processes in socio-technical systems. Here we focus on empirical temporal networks of human proxim- ity and we aim at understanding the factors that, in simulation, shape the arrival time distribution of simple spreading processes. Abandoning the notion of wall-clock time in favour of node-specific clocks based on activ- ity exposes robust statistical patterns in the arrival times across different social contexts. Using randomization strategies and generative models constrained by data, we show that these patterns can be understood in terms of heterogeneous inter-event time distributions coupled with hetero- geneous numbers of events per edge. We also show, both empirically and by using a synthetic dataset, that significant deviations from the above behavior can be caused by the presence of edge classes with strong activity correlations.

  7. Sleep Spindles Characteristics in Insomnia Sufferers and Their Relationship with Sleep Misperception

    Marie-Pier Normand


    Full Text Available Cortical hyperarousal is higher in insomnia sufferers (INS than in good sleepers (GS and could be related to an alteration in sleep protection mechanisms, like reduced density or altered characteristics in sleep spindles. The deficient sleep protection mechanisms might in turn enhance underestimation of sleep. This study’s objective was to document sleep spindles characteristics in INS compared with GS and to investigate their potential role in sleep consolidation and misperception. Seventeen individuals with paradoxical insomnia (PARA-I, 24 individuals with psychophysiological insomnia (PSY-I, and 29 GS completed four consecutive polysomnographic nights in laboratory. Sleep spindles were detected automatically during stage 2 and SWS (3-4 on night 3. Number, density, duration, frequency, and amplitude of sleep spindles were calculated. A misperception index was used to determine the degree of discrepancy between subjective and objective total sleep times. Kruskal-Wallis H tests and post hoc tests revealed that PARA-I had significantly shorter sleep spindles than GS but that PSY-I and GS did not differ on spindles length. A standard multiple regression model revealed that neither sleep spindles characteristics nor objective sleep measures were predictive of sleep misperception. A longer duration of spindles could reflect a higher gating process but this hypothesis still needs to be confirmed in replication studies.

  8. Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation

    van Heesbeen, Roy G H P; Raaijmakers, Jonne A; Tanenbaum, Marvin E; Halim, Vincentius A; Lelieveld, Daphne; Lieftink, Cor; Heck, Albert J R; Egan, David A; Medema, René H


    Inhibition of the microtubule (MT) motor protein Eg5 results in a mitotic arrest due to the formation of monopolar spindles, making Eg5 an attractive target for anti-cancer therapies. However, Eg5-independent pathways for bipolar spindle formation exist, which might promote resistance to treatment w

  9. An allometric analysis of the number of muscle spindles in mammalian skeletal muscles.

    Banks, R W


    An allometric analysis of the number of muscle spindles in relation to muscle mass in mammalian (mouse, rat, guinea-pig, cat, human) skeletal muscles is presented. It is shown that the trend to increasing number as muscle mass increases follows an isometric (length) relationship between species, whereas within a species, at least for the only essentially complete sample (human), the number of spindles scales, on average, with the square root rather than the cube root of muscle mass. An attempt is made to reconcile these apparently discrepant relationships. Use of the widely accepted spindle density (number of spindles g(-1) of muscle) as a measure of relative abundance of spindles in different muscles is shown to be grossly misleading. It is replaced with the residuals of the linear regression of ln spindle number against ln muscle mass. Significant differences in relative spindle abundance as measured by residuals were found between regional groups of muscles: the greatest abundance is in axial muscles, including those concerned with head position, whereas the least is in muscles of the shoulder girdle. No differences were found between large and small muscles operating in parallel, or between antigravity and non-antigravity muscles. For proximal vs. distal muscles, spindles were significantly less abundant in the hand than the arm, but there was no difference between the foot and the leg. PMID:16761976

  10. Sleep Spindles Characteristics in Insomnia Sufferers and Their Relationship with Sleep Misperception


    Cortical hyperarousal is higher in insomnia sufferers (INS) than in good sleepers (GS) and could be related to an alteration in sleep protection mechanisms, like reduced density or altered characteristics in sleep spindles. The deficient sleep protection mechanisms might in turn enhance underestimation of sleep. This study's objective was to document sleep spindles characteristics in INS compared with GS and to investigate their potential role in sleep consolidation and misperception. Seventeen individuals with paradoxical insomnia (PARA-I), 24 individuals with psychophysiological insomnia (PSY-I), and 29 GS completed four consecutive polysomnographic nights in laboratory. Sleep spindles were detected automatically during stage 2 and SWS (3-4) on night 3. Number, density, duration, frequency, and amplitude of sleep spindles were calculated. A misperception index was used to determine the degree of discrepancy between subjective and objective total sleep times. Kruskal-Wallis H tests and post hoc tests revealed that PARA-I had significantly shorter sleep spindles than GS but that PSY-I and GS did not differ on spindles length. A standard multiple regression model revealed that neither sleep spindles characteristics nor objective sleep measures were predictive of sleep misperception. A longer duration of spindles could reflect a higher gating process but this hypothesis still needs to be confirmed in replication studies.

  11. The product of the spindle formation gene sad1+ associates with the fission yeast spindle pole body and is essential for viability


    Spindle formation in fission yeast occurs by the interdigitation of two microtubule arrays extending from duplicated spindle pole bodies which span the nuclear membrane. By screening a bank of temperature-sensitive mutants by anti-tubulin immunofluorescence microscopy, we previously identified the sad1.1 mutation (Hagan, I., and M. Yanagida. 1990. Nature (Lond.). 347:563-566). Here we describe the isolation and characterization of the sad1+ gene. We show that the sad1.1 mutation affected both...

  12. Dynamic positioning system based on active disturbance rejection technology

    Lei, Zhengling; Guo, Chen; Fan, Yunsheng


    A dynamically positioned vessel, by the International Maritime Organization (IMO) and the certifying class societies (DNV, ABS, LR, etc.), is defined as a vessel that maintains its position and heading (fixed location or pre-determined track) exclusively by means of active thrusters. The development of control technology promotes the upgrading of dynamic positioning (DP) systems. Today there are two different DP systems solutions available on the market: DP system based on PID regulator and that based on model-based control. Both systems have limited disturbance rejection capability due to their design principle. In this paper, a new DP system solution is proposed based on Active Disturbance Rejection Control (ADRC) technology. This technology is composed of Tracking-Differentiator (TD), Extended State Observer (ESO) and Nonlinear Feedback Combination. On one hand, both TD and ESO can act as filters and can be used in place of conventional filters; on the other hand, the total disturbance of the system can be estimated and compensated by ESO, which therefore enhances the system's disturbance rejection capability. This technology's advantages over other methods lie in two aspects: 1) This method itself can not only achieve control objectives but also filter noisy measurements without other specialized filters; 2) This method offers a new useful approach to suppress the ocean disturbance. The simulation results demonstrate the effectiveness of the proposed method.

  13. Novel benzimidazole inhibitors bind to a unique site in the kinesin spindle protein motor domain.

    Sheth, Payal R; Shipps, Gerald W; Seghezzi, Wolfgang; Smith, Catherine K; Chuang, Cheng-Chi; Sanden, David; Basso, Andrea D; Vilenchik, Lev; Gray, Kimberly; Annis, D Allen; Nickbarg, Elliott; Ma, Yao; Lahue, Brian; Herbst, Ronald; Le, Hung V


    Affinity selection-mass spectrometry (AS-MS) screening of kinesin spindle protein (KSP) followed by enzyme inhibition studies and temperature-dependent circular dichroism (TdCD) characterization was utilized to identify a series of benzimidazole compounds. This series also binds in the presence of Ispinesib, a known anticancer KSP inhibitor in phase I/II clinical trials for breast cancer. TdCD and AS-MS analyses support simultaneous binding implying existence of a novel non-Ispinesib binding pocket within KSP. Additional TdCD analyses demonstrate direct binding of these compounds to Ispinesib-resistant mutants (D130V, A133D, and A133D + D130V double mutant), further strengthening the hypothesis that the compounds bind to a distinct binding pocket. Also importantly, binding to this pocket causes uncompetitive inhibition of KSP ATPase activity. The uncompetitive inhibition with respect to ATP is also confirmed by the requirement of nucleotide for binding of the compounds. After preliminary affinity optimization, the benzimidazole series exhibited distinctive antimitotic activity as evidenced by blockade of bipolar spindle formation and appearance of monoasters. Cancer cell growth inhibition was also demonstrated either as a single agent or in combination with Ispinesib. The combination was additive as predicted by the binding studies using TdCD and AS-MS analyses. The available data support the existence of a KSP inhibitory site hitherto unknown in the literature. The data also suggest that targeting this novel site could be a productive strategy for eluding Ispinesib-resistant tumors. Finally, AS-MS and TdCD techniques are general in scope and may enable screening other targets in the presence of known drugs, clinical candidates, or tool compounds that bind to the protein of interest in an effort to identify potency-enhancing small molecules that increase efficacy and impede resistance in combination therapy. PMID:20718440

  14. Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division.

    Mora-Bermúdez, Felipe; Matsuzaki, Fumio; Huttner, Wieland B


    Mitotic spindle orientation is crucial for symmetric vs asymmetric cell division and depends on astral microtubules. Here, we show that distinct subpopulations of astral microtubules exist, which have differential functions in regulating spindle orientation and division symmetry. Specifically, in polarized stem cells of developing mouse neocortex, astral microtubules reaching the apical and basal cell cortex, but not those reaching the central cell cortex, are more abundant in symmetrically than asymmetrically dividing cells and reduce spindle orientation variability. This promotes symmetric divisions by maintaining an apico-basal cleavage plane. The greater abundance of apical/basal astrals depends on a higher concentration, at the basal cell cortex, of LGN, a known spindle-cell cortex linker. Furthermore, newly developed specific microtubule perturbations that selectively decrease apical/basal astrals recapitulate the symmetric-to-asymmetric division switch and suffice to increase neurogenesis in vivo. Thus, our study identifies a novel link between cell polarity, astral microtubules, and spindle orientation in morphogenesis. PMID:24996848

  15. Quantifying unsteadiness and dynamics of pulsatory volcanic activity

    Dominguez, L.; Pioli, L.; Bonadonna, C.; Connor, C. B.; Andronico, D.; Harris, A. J. L.; Ripepe, M.


    Pulsatory eruptions are marked by a sequence of explosions which can be separated by time intervals ranging from a few seconds to several hours. The quantification of the periodicities associated with these eruptions is essential not only for the comprehension of the mechanisms controlling explosivity, but also for classification purposes. We focus on the dynamics of pulsatory activity and quantify unsteadiness based on the distribution of the repose time intervals between single explosive events in relation to magma properties and eruptive styles. A broad range of pulsatory eruption styles are considered, including Strombolian, violent Strombolian and Vulcanian explosions. We find a general relationship between the median of the observed repose times in eruptive sequences and the viscosity of magma given by η ≈ 100 ṡtmedian. This relationship applies to the complete range of magma viscosities considered in our study (102 to 109 Pa s) regardless of the eruption length, eruptive style and associated plume heights, suggesting that viscosity is the main magma property controlling eruption periodicity. Furthermore, the analysis of the explosive sequences in terms of failure time through statistical survival analysis provides further information: dynamics of pulsatory activity can be successfully described in terms of frequency and regularity of the explosions, quantified based on the log-logistic distribution. A linear relationship is identified between the log-logistic parameters, μ and s. This relationship is useful for quantifying differences among eruptive styles from very frequent and regular mafic events (Strombolian activity) to more sporadic and irregular Vulcanian explosions in silicic systems. The time scale controlled by the parameter μ, as a function of the median of the distribution, can be therefore correlated with the viscosity of magmas; while the complexity of the erupting system, including magma rise rate, degassing and fragmentation efficiency

  16. DNA damage response and spindle assembly checkpoint function throughout the cell cycle to ensure genomic integrity.

    Katherine S Lawrence


    Full Text Available Errors in replication or segregation lead to DNA damage, mutations, and aneuploidies. Consequently, cells monitor these events and delay progression through the cell cycle so repair precedes division. The DNA damage response (DDR, which monitors DNA integrity, and the spindle assembly checkpoint (SAC, which responds to defects in spindle attachment/tension during metaphase of mitosis and meiosis, are critical for preventing genome instability. Here we show that the DDR and SAC function together throughout the cell cycle to ensure genome integrity in C. elegans germ cells. Metaphase defects result in enrichment of SAC and DDR components to chromatin, and both SAC and DDR are required for metaphase delays. During persistent metaphase arrest following establishment of bi-oriented chromosomes, stability of the metaphase plate is compromised in the absence of DDR kinases ATR or CHK1 or SAC components, MAD1/MAD2, suggesting SAC functions in metaphase beyond its interactions with APC activator CDC20. In response to DNA damage, MAD2 and the histone variant CENPA become enriched at the nuclear periphery in a DDR-dependent manner. Further, depletion of either MAD1 or CENPA results in loss of peripherally associated damaged DNA. In contrast to a SAC-insensitive CDC20 mutant, germ cells deficient for SAC or CENPA cannot efficiently repair DNA damage, suggesting that SAC mediates DNA repair through CENPA interactions with the nuclear periphery. We also show that replication perturbations result in relocalization of MAD1/MAD2 in human cells, suggesting that the role of SAC in DNA repair is conserved.

  17. Low-dimensional dynamics of resting-state cortical activity.

    Mehrkanoon, Saeid; Breakspear, Michael; Boonstra, Tjeerd W


    Endogenous brain activity supports spontaneous human thought and shapes perception and behavior. Connectivity-based analyses of endogenous, or resting-state, functional magnetic resonance imaging (fMRI) data have revealed the existence of a small number of robust networks which have a rich spatial structure. Yet the temporal information within fMRI data is limited, motivating the complementary analysis of electrophysiological recordings such as electroencephalography (EEG). Here we provide a novel method based on multivariate time-frequency interdependence to reconstruct the principal resting-state network dynamics in human EEG data. The stability of network expression across subjects is assessed using resampling techniques. We report the presence of seven robust networks, with distinct topographic organizations and high frequency (∼ 5-45 Hz) fingerprints, nested within slow temporal sequences that build up and decay over several orders of magnitude. Interestingly, all seven networks are expressed concurrently during these slow dynamics, although there is a temporal asymmetry in the pattern of their formation and dissolution. These analyses uncover the complex temporal character of endogenous cortical fluctuations and, in particular, offer an opportunity to reconstruct the low dimensional linear subspace in which they unfold. PMID:24104726

  18. Active microrheology of Brownian suspensions via Accelerated Stokesian Dynamics simulations

    Chu, Henry; Su, Yu; Gu, Kevin; Hoh, Nicholas; Zia, Roseanna


    The non-equilibrium rheological response of colloidal suspensions is studied via active microrheology utilizing Accelerated Stokesian Dynamics simulations. In our recent work, we derived the theory for micro-diffusivity and suspension stress in dilute suspensions of hydrodynamically interacting colloids. This work revealed that force-induced diffusion is anisotropic, with qualitative differences between diffusion along the line of the external force and that transverse to it, and connected these effects to the role of hydrodynamic, interparticle, and Brownian forces. This work also revealed that these forces play a similar qualitative role in the anisotropy of the stress and in the evolution of the non-equilibrium osmotic pressure. Here, we show that theoretical predictions hold for suspensions ranging from dilute to near maximum packing, and for a range of flow strengths from near-equilibrium to the pure-hydrodynamic limit.

  19. Modelling of piezoelectric actuator dynamics for active structural control

    Hagood, Nesbitt W.; Chung, Walter H.; Von Flotow, Andreas


    The paper models the effects of dynamic coupling between a structure and an electrical network through the piezoelectric effect. The coupled equations of motion of an arbitrary elastic structure with piezoelectric elements and passive electronics are derived. State space models are developed for three important cases: direct voltage driven electrodes, direct charge driven electrodes, and an indirect drive case where the piezoelectric electrodes are connected to an arbitrary electrical circuit with embedded voltage and current sources. The equations are applied to the case of a cantilevered beam with surface mounted piezoceramics and indirect voltage and current drive. The theoretical derivations are validated experimentally on an actively controlled cantilevered beam test article with indirect voltage drive.

  20. An analogy between optical turbulence and activator-inhibitor dynamics

    Spineanu, F


    The propagation of laser beams through madia with cubic nonlinear polarization is part of a wide range of practical applications. The processes that are involved are at the limit of extreme (cuasi-singular) concentration of intensity and the transversal modulational instability, the saturation and defocusing effect of the plasma generated through avalanche and multi-photon (MPI) ionization are competing leading to a complicated pattern of intensity in the transversal plane. This regime has been named \\textquotedblleft optical turbulence\\textquotedblright and it has been studied in experiments and numerical simulations. Led by the similarity of the portraits we have investigated the possibility that the mechanism that underlies the creation of the complex pattern of the intensity field is the manifestation of the dynamics \\textit{activator-inhibitor}. In a previous work we have considered a unique connection, the \\textit{complex Landau-Ginzburg equation}, a common ground for the nonlinear Schrodinger equation ...

  1. High resolution dynamical mapping of social interactions with active RFID

    Barrat, Alain; Colizza, Vittoria; Pinton, Jean-Francois; Broeck, Wouter Van den; Vespignani, Alessandro


    In this paper we present an experimental framework to gather data on face-to-face social interactions between individuals, with a high spatial and temporal resolution. We use active Radio Frequency Identification (RFID) devices that assess contacts with one another by exchanging low-power radio packets. When individuals wear the beacons as a badge, a persistent radio contact between the RFID devices can be used as a proxy for a social interaction between individuals. We present the results of a pilot study %recently performed during a conference, and a subsequent preliminary data analysis, that provides an assessment of our method and highlights its versatility and applicability in many areas concerned with human dynamics.

  2. Role of mechanical activation in the dynamic transformation of austenite

    When austenite is deformed above the equilibrium transformation temperature Ae3, it is dynamically transformed into Widmanstätten ferrite by a displacive mechanism. On removal of the load it is slowly retransformed into austenite by diffusional processes. The forward transformation has recently been explained in terms of a thermodynamic model in which the lower free energy of austenite is raised above that of normally unstable ferrite as a result of the additional stored energy associated with the dislocations introduced by straining. This model is here shown to be unable to account for the initiation of transformation at critical strains of about 0.1, at which only low densities of dislocations are present. Of particular importance is the observation that dynamic transformation can be initiated at temperatures 100 °C and more above the Ae3 and that the critical strain actually decreases with increasing temperature and increasing chemical free energy barrier. This discrepancy is removed by allowing for mechanical (stress-based) activation of the transformation. The latter provides the energy required to accommodate the shear of the parent austenite into Widmanstätten plates, as well as the volume change or dilatation accompanying ferrite formation. The work of dilatation and the shear accommodation work, omitted from the previous analysis, are introduced here as barriers to the transformation that are overcome by the applied stress. This modified approach is able to account for the very rapid forward (mechanically activated) transformation compared with the much slower reverse transformation that takes place in the absence of stress

  3. Chromokinesin: Kinesin superfamily regulating cell division through chromosome and spindle.

    Zhong, Ai; Tan, Fu-Qing; Yang, Wan-Xi


    Material transportation is essential for appropriate cellular morphology and functions, especially during cell division. As a motor protein moving along microtubules, kinesin has several intracellular functions. Many kinesins play important roles in chromosome condensation and separation and spindle organization during the cell cycle. Some of them even can directly bind to chromosomes, as a result, these proteins are called chromokinesins. Kinesin-4 and kinesin-10 family are two major families of chromokinesin and many members can regulate some processes, both in mitosis and meiosis. Their functions have been widely studied. Here, we summarize current knowledge about known chromokinesins and introduce their intracellular features in accordance with different families. Furthermore, we have also introduced some new-found but unconfirmed kinesins which may have a relationship with chromosomes or the cell cycle. PMID:27196062

  4. Sleep spindles and hippocampal functional connectivity in human NREM sleep.

    Andrade, Kátia C; Spoormaker, Victor I; Dresler, Martin; Wehrle, Renate; Holsboer, Florian; Sämann, Philipp G; Czisch, Michael


    We investigated human hippocampal functional connectivity in wakefulness and throughout non-rapid eye movement sleep. Young healthy subjects underwent simultaneous EEG and functional magnetic resonance imaging (fMRI) measurements at 1.5 T under resting conditions in the descent to deep sleep. Continuous 5 min epochs representing a unique sleep stage (i.e., wakefulness, sleep stages 1 and 2, or slow-wave sleep) were extracted. fMRI time series of subregions of the hippocampal formation (HF) (cornu ammonis, dentate gyrus, and subiculum) were extracted based on cytoarchitectonical probability maps. We observed sleep stage-dependent changes in HF functional coupling. The HF was integrated to variable strength in the default mode network (DMN) in wakefulness and light sleep stages but not in slow-wave sleep. The strongest functional connectivity between the HF and neocortex was observed in sleep stage 2 (compared with both slow-wave sleep and wakefulness). We observed a strong interaction of sleep spindle occurrence and HF functional connectivity in sleep stage 2, with increased HF/neocortical connectivity during spindles. Moreover, the cornu ammonis exhibited strongest functional connectivity with the DMN during wakefulness, while the subiculum dominated hippocampal functional connectivity to frontal brain regions during sleep stage 2. Increased connectivity between HF and neocortical regions in sleep stage 2 suggests an increased capacity for possible global information transfer, while connectivity in slow-wave sleep is reflecting a functional system optimal for segregated information reprocessing. Our data may be relevant to differentiating sleep stage-specific contributions to neural plasticity as proposed in sleep-dependent memory consolidation. PMID:21753010

  5. Aurora A kinase regulates proper spindle positioning in C. elegans and in human cells.

    Kotak, Sachin; Afshar, Katayon; Busso, Coralie; Gönczy, Pierre


    Accurate spindle positioning is essential for error-free cell division. The one-cell Caenorhabditis elegans embryo has proven instrumental for dissecting mechanisms governing spindle positioning. Despite important progress, how the cortical forces that act on astral microtubules to properly position the spindle are modulated is incompletely understood. Here, we report that the PP6 phosphatase PPH-6 and its associated subunit SAPS-1, which positively regulate pulling forces acting on spindle poles, associate with the Aurora A kinase AIR-1 in C. elegans embryos. We show that acute inactivation of AIR-1 during mitosis results in excess pulling forces on astral microtubules. Furthermore, we uncover that AIR-1 acts downstream of PPH-6-SAPS-1 in modulating spindle positioning, and that PPH-6-SAPS-1 negatively regulates AIR-1 localization at the cell cortex. Moreover, we show that Aurora A and the PP6 phosphatase subunit PPP6C are also necessary for spindle positioning in human cells. There, Aurora A is needed for the cortical localization of NuMA and dynein during mitosis. Overall, our work demonstrates that Aurora A kinases and PP6 phosphatases have an ancient function in modulating spindle positioning, thus contributing to faithful cell division. PMID:27335426

  6. A new method to measure circular runout of end-milling spindle based on cutting mark

    Zhou, Jianlai; Liu, Shuchun


    A practical method is introduced to measure the circular runout of a end-milling spindle system at high speed rotations without the need of a reference sphere. A workpiece is held on a linear slide which moves along the axial direction of the spindle. The spindle is then programmed to run at a specific speed. A very sharp edge cutter must be used and the depth of cut will be very shallow in order to keep the cutting force very small. The workpiece is then fed into the end mill in order to make a cutting mark of teens μm in depth. The cutting marks are circular, and their diameters are related to the circular runout of the spindle system. The cutting mark that is generated at a specific speed is expected to contain information about the spindle circular runout at this speed. In practice the cutting marks are not perfectly circular. Therefore, a best-fit circle of a cutting mark is needed to determine its diameter. A high-resolution edge detector machine is used for this purpose. Quantitative precision analysis was carried out to confirm the accuracy and repeatability of this new measurement technique. It is demonstrated that this technique for the measurement of spindle circular runout is an effective tool in verifying the actual running accuracy of spindles at their actual operating speeds and can be accomplished without the need for a reference sphere.

  7. DDA3 targets Cep290 into the centrosome to regulate spindle positioning.

    Song, Haiyu; Park, Ji Eun; Jang, Chang-Young

    The centrosome is an important cellular organelle which nucleates microtubules (MTs) to form the cytoskeleton during interphase and the mitotic spindle during mitosis. The Cep290 is one of the centrosomal proteins and functions in cilia formation. Even-though it is in the centrosome, the function of Cep290 in mitosis had not yet been evaluated. In this study, we report a novel function of Cep290 that is involved in spindle positioning. Cep290 was identified as an interacting partner of DDA3, and we confirmed that Cep290 specifically localizes in the mitotic centrosome. Depletion of Cep290 caused a reduction of the astral spindle, leading to misorientation of the mitotic spindle. MT polymerization also decreased in Cep290-depleted cells, suggesting that Cep290 is involved in spindle nucleation. Furthermore, DDA3 stabilizes and transports Cep290 to the centrosome. Therefore, we concluded that DDA3 controls astral spindle formation and spindle positioning by targeting Cep290 to the centrosome. PMID:25998387

  8. Meiosis in a triploid hybrid of Gossypium: high frequency of secondary bipolar spindles at metaphase II

    Mosareza Vafaie-Tabar; Shanti Chandrashekaran


    Studies on meiosis in pollen mother cells (PMCs) of a triploid interspecific hybrid ($3x = 39$ chromosomes, AAD) between tetraploid Gossypium hirsutum ($4n = 2x = 52$,AADD) and diploid G. arboreum ($2n = 2x = 26$,AA) are reported. During meiotic metaphase I, 13 AA bivalents and 13 D univalents are expected in the hybrid. However, only 28% of the PMCs had this expected configuration. The rest of the PMCs had between 8 and 12 bivalents and between 12 and 17 univalents. Univalents lagged at anaphase I, and at metaphase II one or a group of univalents remained scattered in the cytoplasm and failed to assemble at a single metaphase plate. Primary bipolar spindles organized around the bivalents and multivalents. In addition to the primary spindle, several secondary and smaller bipolar spindles organized themselves around individual univalents and groups of univalents. Almost all (97%) of the PMCs showed secondary spindles. Each spindle functioned independently and despite their multiple numbers in a cell, meiosis I proceeded normally, with polyad formation. These observations strongly support the view that in plant meiocytes bilateral kinetochore symmetry is not required for establishing a bipolar spindle and that single unpaired chromosomes can initiate and stabilize the formation of a functional bipolar spindle.

  9. HBT-EP Program: Active MHD Mode Dynamics and Control

    Navratil, G. A.; Bialek, J.; Boozer, A. H.; Byrne, P. J.; Donald, G. V.; Hughes, P. E.; Levesque, J. P.; Mauel, M. E.; Peng, Q.; Rhodes, D. J.; Stoafer, C. C.; Hansen, C. J.


    The HBT-EP active mode control research program aims to: (i) quantify external kink dynamics and multimode response to magnetic perturbations, (ii) understand the relationship between control coil configuration, conducting and ferritic wall effects, and active feedback control, and (iii) explore advanced feedback algorithms. Biorthogonal decomposition is used to observe multiple simultaneous resistive wall modes (RWM). A 512 core GPU-based low latency (14 μs) MIMO control system uses 96 inputs and 64 outputs for Adaptive Control of RWMs. An in-vessel adjustable ferritic wall is used to study ferritic RWMs with increased growth rates, RMP response, and disruptivity. A biased electrode in the plasma is used to control the rotation of external kinks and evaluate error fields. A Thomson scattering diagnostic measures Te and ne at 3 spatial points, soon to be extended to 10 points. A quasi-linear sharp-boundary model of the plasma's multimode response to error fields is developed to determine harmful error field structures and associated NTV and resonant torques. Upcoming machine upgrades will allow measurements and control of scrape-off-layer currents, and control of kink modes using optical diagnostics. Supported by U.S. DOE Grant DE-FG02-86ER53222.

  10. Spatiotemporal dynamics of large-scale brain activity

    Neuman, Jeremy

    Understanding the dynamics of large-scale brain activity is a tough challenge. One reason for this is the presence of an incredible amount of complexity arising from having roughly 100 billion neurons connected via 100 trillion synapses. Because of the extremely high number of degrees of freedom in the nervous system, the question of how the brain manages to properly function and remain stable, yet also be adaptable, must be posed. Neuroscientists have identified many ways the nervous system makes this possible, of which synaptic plasticity is possibly the most notable one. On the other hand, it is vital to understand how the nervous system also loses stability, resulting in neuropathological diseases such as epilepsy, a disease which affects 1% of the population. In the following work, we seek to answer some of these questions from two different perspectives. The first uses mean-field theory applied to neuronal populations, where the variables of interest are the percentages of active excitatory and inhibitory neurons in a network, to consider how the nervous system responds to external stimuli, self-organizes and generates epileptiform activity. The second method uses statistical field theory, in the framework of single neurons on a lattice, to study the concept of criticality, an idea borrowed from physics which posits that in some regime the brain operates in a collectively stable or marginally stable manner. This will be examined in two different neuronal networks with self-organized criticality serving as the overarching theme for the union of both perspectives. One of the biggest problems in neuroscience is the question of to what extent certain details are significant to the functioning of the brain. These details give rise to various spatiotemporal properties that at the smallest of scales explain the interaction of single neurons and synapses and at the largest of scales describe, for example, behaviors and sensations. In what follows, we will shed some

  11. Tax Evasion Dynamics in Romania Reflected by Fiscal Inspection Activities



    Full Text Available The paper aims to provide a panoramic view of the dynamics of tax evasion in Romania, reflected in terms of fiscal inspection activities. The author used the official data published by the institutions with attributions on the line of identification and fighting against tax evasion (National Agency of Fiscal Administration and Financial Guard with the view to reflect the real situation concerning the number of inspections, quantify and sanction tax evasion for 2003-2008 periods. Although the number of fiscal inspections and the number of tax payers who have violated the rules of fiscal discipline decreased compared with 2003, the frequency of tax evasion remained. At the same time, based on the data referring to the level and dynamics of the tax dodger phenomenon appreciations have been made regarding the fiscal discipline of the Romanian tax payer and to the attitude of the qualified institutions in discovering and sanctioning the fraudulent tax evasion. In this respect, the author observed that the level of willingness of tax legislation in relation to the Romanian tax payer has not changed considerably.The level of identified tax evasion reported to real GDP increased slightly. This situation can be interpreted as a success of institutions in charge of identification and fighting of tax evasion, a result of the increase of fiscal inspection number and detection probability, but also a result of GDP growth at a rate lower than the identified tax evasion. The author has also tried to find a causality relation between the option for tax evasion and corruption. The author found that a corrupt environment facilitates the decision to evade depending on detection probability, penalty system and bribery level as discouraging factors for tax evasion. The level of identified tax evasion is smaller than the real level of entire tax evasion, an important part being impossible to determine because of corruption.

  12. Dynamic hyperinflation during activities of daily living in COPD patients.

    Silva, Cláudia S; Nogueira, Fabiana R; Porto, Elias F; Gazzotti, Mariana R; Nascimento, Oliver A; Camelier, Aquiles; Jardim, José R


    The objective of this study was to investigate whether some activities of daily living (ADLs) usually related to dyspnea sensation in patients with chronic obstructive pulmonary disease (COPD) are associated with dynamic lung hyperinflation (DH) and whether the use of simple energy conservation techniques (ECTs) might reduce this possible hyperinflation. Eighteen patients (mean age: 65.8 ± 9.8 years) with moderate-to-severe COPD performed six ADLs (walking on a treadmill, storing pots, walking 56 meters carrying a 5-kilogram weight, climbing stairs, simulating taking a shower, and putting on shoes) and had their inspiratory capacity (IC) measured before and after each task. The patients were moderately obstructed with forced expiratory volume in 1 second (FEV1): 1.4 ± 0.4 L (50% ± 12.4); FEV1/forced vital capacity: 0.4 ± 8.1; residual volume/total lung capacity: 52.7 ± 10.2, and a reduction in IC was seen after all six activities (p < 0.05): (1) going upstairs, 170 mL; (2) walking 56 meters carrying 5 kilogram weight, 150 mL; (3) walking on a treadmill without and with ECT, respectively, 230 mL and 235 mL; (4) storing pots without and with ECT, respectively, 170 mL and 128 mL; (5) taking a shower without and with ECT, respectively, 172 mL and 118 mL; and (6) putting on shoes without and with ECT, respectively, 210 mL and 78 mL). Patients with moderate to severe COPD develop DH after performing common ADLs involving the upper and lower limbs. Simple ECTs may avoid DH in some of these ADLs. PMID:25896955

  13. A Dynamical Training and Design Simulator for Active Catheters

    Georges Dumont


    Full Text Available This work addresses the design of an active multi-link micro-catheter actuated by Shape Memory Alloy (SMA micro actuators. This may be a response to one medical major demand on such devices, which will be useful for surgical explorations and interventions. In this paper, we focus on a training and design simulator dedicated to such catheters. This simulator is based on an original simulation platform (OpenMASK. The catheter is a robotic system, which is evaluated by a dynamical simulation addressing a navigation task in its environment. The design of the prototype and its mechanical model are presented. We develop an interaction model for contact. This model uses a real medical database for which distance cartography is proposed. Then we focus on an autonomous control model based on a multi-agent approach and including the behaviour description of the SMA actuators. Results of mechanical simulations including interaction with the ducts are presented. Furthermore, the interest of such a simulator is presented by applying virtual prototyping techniques for the design optimization. This optimization process is achieved by using genetic algorithms at different stages with respect to the specified task.

  14. Dynamical Delays Between Starburst and AGN Activity in Galaxy Nuclei

    Hopkins, Philip F


    Observations of AGN have suggested a possible delay between the peak of star formation (on some scale) and AGN activity. Feedback from fast stellar winds has been invoked to explain this, but this is not likely to be viable in bright systems accreting primarily cold dense gas. We show that such a delay can arise even in bright quasars for purely dynamical reasons. If some large-scale process produces rapid inflow, smaller scales will quickly become gas-dominated. As the gas density peaks, so does the SFR. However, gravitational torques which govern further inflow are relatively inefficient in gas-dominated systems; as more gas is turned into stars, the stars provide an efficient angular momentum sink allowing more rapid inflow. Moreover, the gas provided to the central regions in mergers or strong disk instabilities will typically be ~100 times larger than that needed to fuel the BH; the system is effectively in the 'infinite gas supply' limit. BH growth can therefore continue for some time while the gas supp...

  15. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    Highlights: → The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. → This SAP-like domain is essential for chromosome loading during early mitosis. → NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. → The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction

  16. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    Verbakel, Werner, E-mail: [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium); Carmeliet, Geert, E-mail: [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium); Engelborghs, Yves, E-mail: [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)


    Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase Nu

  17. Sleep-spindle detection: crowdsourcing and evaluating performance of experts, non-experts and automated methods

    Warby, Simon C.; Wendt, Sabrina Lyngbye; Welinder, Peter;


    crowdsource spindle identification by human experts and non-experts, and we compared their performance with that of automated detection algorithms in data from middle- to older-aged subjects from the general population. We also refined methods for forming group consensus and evaluating the performance of...... that crowdsourcing the scoring of sleep data is an efficient method to collect large data sets, even for difficult tasks such as spindle identification. Further refinements to spindle detection algorithms are needed for middle- to older-aged subjects....... event detectors in physiological data such as electroencephalographic recordings from polysomnography. Compared to the expert group consensus gold standard, the highest performance was by individual experts and the non-expert group consensus, followed by automated spindle detectors. This analysis showed...

  18. Sleep Spindles Characteristics in Insomnia Sufferers and Their Relationship with Sleep Misperception

    Normand, Marie-Pier; St-Hilaire, Patrick; Célyne H. Bastien


    Cortical hyperarousal is higher in insomnia sufferers (INS) than in good sleepers (GS) and could be related to an alteration in sleep protection mechanisms, like reduced density or altered characteristics in sleep spindles. The deficient sleep protection mechanisms might in turn enhance underestimation of sleep. This study’s objective was to document sleep spindles characteristics in INS compared with GS and to investigate their potential role in sleep consolidation and misperception. Sevente...

  19. An AFM-based methodology for measuring axial and radial error motions of spindles

    This paper presents a novel atomic force microscopy (AFM)-based methodology for measurement of axial and radial error motions of a high precision spindle. Based on a modified commercial AFM system, the AFM tip is employed as a cutting tool by which nano-grooves are scratched on a flat surface with the rotation of the spindle. By extracting the radial motion data of the spindle from the scratched nano-grooves, the radial error motion of the spindle can be calculated after subtracting the tilting errors from the original measurement data. Through recording the variation of the PZT displacement in the Z direction in AFM tapping mode during the spindle rotation, the axial error motion of the spindle can be obtained. Moreover the effects of the nano-scratching parameters on the scratched grooves, the tilting error removal method for both conditions and the method of data extraction from the scratched groove depth are studied in detail. The axial error motion of 124 nm and the radial error motion of 279 nm of a commercial high precision air bearing spindle are achieved by this novel method, which are comparable with the values provided by the manufacturer, verifying this method. This approach does not need an expensive standard part as in most conventional measurement approaches. Moreover, the axial and radial error motions of the spindle can both be obtained, indicating that this is a potential means of measuring the error motions of the high precision moving parts of ultra-precision machine tools in the future. (paper)

  20. Sources of innervation of the neuromuscular spindles in sternomastoid and trapezius.

    FitzGerald, M J; Comerford, P T; Tuffery, A R


    The sources of innervation of neuromuscular spindles in sternomastoid and trapezius have been investigated in rats and mice, by degeneration experiments. The entire motor supply, both extrafusal and intrafusal, to both muscles, was from the spinal accessory nerve. The sensory supply to the spindles in sternomastoid and rostral trapezius was from cervical spinal nerves, and to those in the caudal trapezius was from thoracic spinal nerves.

  1. Interphase adhesion geometry is transmitted to an internal regulator for spindle orientation via caveolin-1

    Matsumura, Shigeru; Kojidani, Tomoko; Kamioka, Yuji; Uchida, Seiichi; Haraguchi, Tokuko; Kimura, Akatsuki; Toyoshima, Fumiko


    Despite theoretical and physical studies implying that cell-extracellular matrix adhesion geometry governs the orientation of the cell division axis, the molecular mechanisms that translate interphase adhesion geometry to the mitotic spindle orientation remain elusive. Here, we show that the cellular edge retraction during mitotic cell rounding correlates with the spindle axis. At the onset of mitotic cell rounding, caveolin-1 is targeted to the retracting cortical region at the proximal end ...

  2. Somatic and intramuscular distribution of muscle spindles and their relation to muscular angiotypes.

    Kokkorogiannis, Theodoros


    The distribution pattern of muscle spindles in the skeletal musculature has been reviewed in a large number of muscles (using the literature data especially from cat and man), and the relation of spindle content to muscle mass was quantitatively examined in 36 cat and 140 human muscles. In both species, the number of spindles increases with increasing muscle mass in a power law fashion of the form y=bx+a, whereby y denotes the logarithm of spindle content within a muscle, and x is the logarithm of muscle mass. For the cat, slope b and intercept a were estimated as 0.39 and 1.53, and for man as 0.48 and 1.33, respectively. The results show that the spindle content of a muscle may be related to its mass, confirming a similar analysis made previously by Banks and Stacey (Mechano receptors, Plenum Press, New York, 1988, pp. 263-269) in a different data set. With regard to the histological profile of muscle fibers, (as it is already well documented by many groups) muscle spindles tend to be located in deeper muscle regions where oxidative fibers predominate, and are far scarcer in superficial and flat muscle regions where glycolytic fibers predominate. These discrete muscle regions differ also in the properties of the vessel tree supplying them, for which the term oxidative and glycolytic "angiotype" has been used. The results from these three aspects of analysis (relation to muscle mass, relation to muscle regions with high oxidative index and relation to muscle regions with dense vascular supply) were combined with histological findings showing that spindles may be in systematic anatomical contact to intramuscular vessels. Based on these data a hypothesis is proposed according to which, both the number and intramuscular placement of muscle spindles are related to the oxidative angiotype supplying the muscle territories rich in oxidative fibers. The hypothesis is discussed. PMID:15207480

  3. Mitotic spindle asymmetry in rodents and primates: 2D vs. 3D measurement methodologies

    Delphine eDelaunay; Robini, Marc C.; Colette eDehay


    Recent data have uncovered that spindle size asymmetry (SSA) is a key component of asymmetric cell division (ACD) in the mouse cerebral cortex (Delaunay et al., 2014). In the present study we show that SSA is independent of spindle orientation and also occurs during cortical progenitor divisions in the ventricular zone (VZ) of the macaque cerebral cortex, pointing to a conserved mechanism in the mammalian lineage. Because SSA magnitude is smaller in cortical precursors than in invertebrate ne...

  4. Muscle spindles in the jaw-closer muscles of the domestic cat.

    Burhanudin, R; McDonald, F.; Rowlerson, A.


    The objectives of this study were to identify the exact location of spindles in jaw-closer muscles of the cat, to count the total number of spindles and to compare their distribution with the distribution of slow extrafusal fibres. The jaw-closer muscle group with all the skeletal attachments intact was fixed in a modified Carnoy solution, decalcified and processed through to wax. Complete series of sections were cut transverse, sagittal and perpendicular to the anterior temporalis muscle. At...

  5. High-Speed Spindle Fault Diagnosis with the Empirical Mode Decomposition and Multiscale Entropy Method

    Nan-Kai Hsieh; Wei-Yen Lin; Hong-Tsu Young


    The root mean square (RMS) value of a vibration signal is an important indicator used to represent the amplitude of vibrations in evaluating the quality of high-speed spindles. However, RMS is unable to detect a number of common fault characteristics that occur prior to bearing failure. Extending the operational life and quality of spindles requires reliable fault diagnosis techniques for the analysis of vibration signals from three axes. This study used empirical mode decomposition to decomp...

  6. 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...

  7. The Contribution of Thalamocortical Core and Matrix Pathways to Sleep Spindles.

    Piantoni, Giovanni; Halgren, Eric; Cash, Sydney S


    Sleep spindles arise from the interaction of thalamic and cortical neurons. Neurons in the thalamic reticular nucleus (TRN) inhibit thalamocortical neurons, which in turn excite the TRN and cortical neurons. A fundamental principle of anatomical organization of the thalamocortical projections is the presence of two pathways: the diffuse matrix pathway and the spatially selective core pathway. Cortical layers are differentially targeted by these two pathways with matrix projections synapsing in superficial layers and core projections impinging on middle layers. Based on this anatomical observation, we propose that spindles can be classified into two classes, those arising from the core pathway and those arising from the matrix pathway, although this does not exclude the fact that some spindles might combine both pathways at the same time. We find evidence for this hypothesis in EEG/MEG studies, intracranial recordings, and computational models that incorporate this difference. This distinction will prove useful in accounting for the multiple functions attributed to spindles, in that spindles of different types might act on local and widespread spatial scales. Because spindle mechanisms are often hijacked in epilepsy and schizophrenia, the classification proposed in this review might provide valuable information in defining which pathways have gone awry in these neurological disorders. PMID:27144033

  8. Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

    Wise, Merrill S.


    Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population.

  9. A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells.

    Hehnly, Heidi; Canton, David; Bucko, Paula; Langeberg, Lorene K; Ogier, Leah; Gelman, Irwin; Santana, L Fernando; Wordeman, Linda; Scott, John D


    Correct orientation of the mitotic spindle in stem cells underlies organogenesis. Spindle abnormalities correlate with cancer progression in germ line-derived tumors. We discover a macromolecular complex between the scaffolding protein Gravin/AKAP12 and the mitotic kinases, Aurora A and Plk1, that is down regulated in human seminoma. Depletion of Gravin correlates with an increased mitotic index and disorganization of seminiferous tubules. Biochemical, super-resolution imaging, and enzymology approaches establish that this Gravin scaffold accumulates at the mother spindle pole during metaphase. Manipulating elements of the Gravin-Aurora A-Plk1 axis prompts mitotic delay and prevents appropriate assembly of astral microtubules to promote spindle misorientation. These pathological responses are conserved in seminiferous tubules from Gravin(-/-) mice where an overabundance of Oct3/4 positive germ line stem cells displays randomized orientation of mitotic spindles. Thus, we propose that Gravin-mediated recruitment of Aurora A and Plk1 to the mother (oldest) spindle pole contributes to the fidelity of symmetric cell division. PMID:26406118

  10. The Contribution of Thalamocortical Core and Matrix Pathways to Sleep Spindles

    Piantoni, Giovanni; Halgren, Eric; Cash, Sydney S.


    Sleep spindles arise from the interaction of thalamic and cortical neurons. Neurons in the thalamic reticular nucleus (TRN) inhibit thalamocortical neurons, which in turn excite the TRN and cortical neurons. A fundamental principle of anatomical organization of the thalamocortical projections is the presence of two pathways: the diffuse matrix pathway and the spatially selective core pathway. Cortical layers are differentially targeted by these two pathways with matrix projections synapsing in superficial layers and core projections impinging on middle layers. Based on this anatomical observation, we propose that spindles can be classified into two classes, those arising from the core pathway and those arising from the matrix pathway, although this does not exclude the fact that some spindles might combine both pathways at the same time. We find evidence for this hypothesis in EEG/MEG studies, intracranial recordings, and computational models that incorporate this difference. This distinction will prove useful in accounting for the multiple functions attributed to spindles, in that spindles of different types might act on local and widespread spatial scales. Because spindle mechanisms are often hijacked in epilepsy and schizophrenia, the classification proposed in this review might provide valuable information in defining which pathways have gone awry in these neurological disorders.

  11. Age-related Changes In Sleep Spindles Characteristics During Daytime Recovery Following a 25-Hour Sleep Deprivation

    Thaïna eRosinvil


    Full Text Available Objectives: The mechanisms underlying sleep spindles (~11-15Hz; >0.5s help to protect sleep. With age, it becomes increasingly difficult to maintain sleep at a challenging time (e.g. daytime, even after sleep loss. This study compared spindle characteristics during daytime recovery and nocturnal sleep in young and middle-aged adults. In addition, we explored whether spindles characteristics in baseline nocturnal sleep were associated with the ability to maintain sleep during daytime recovery periods in both age groups.Methods: Twenty-nine young (15 women and 14 men; 27.3 ± 5.0 and 31 middle-aged (19 women and 13 men; 51.6 y ± 5.1 healthy subjects participated in a baseline nocturnal sleep and a daytime recovery sleep after 25 hours of sleep deprivation. Spindles were detected on artefact-free NREM sleep epochs. Spindle density (nb/min, amplitude (μV, frequency (Hz and duration (s were analyzed on parasagittal (linked-ears derivations. Results: In young subjects, spindle frequency increased during daytime recovery sleep as compared to baseline nocturnal sleep in all derivations, whereas middle-aged subjects showed spindle frequency enhancement only in the prefrontal derivation. No other significant interaction between age group and sleep condition was observed. Spindle density for all derivations and centro-occipital spindle amplitude decreased whereas prefrontal spindle amplitude increased from baseline to daytime recovery sleep in both age groups. Finally, no significant correlation was found between spindle characteristics during baseline nocturnal sleep and the marked reduction in sleep efficiency during daytime recovery sleep in both young and middle-aged subjects.Conclusion: These results suggest that the interaction between homeostatic and circadian pressure module spindle frequency differently in aging. Spindle characteristics do not seem to be linked with the ability to maintain daytime recovery sleep.

  12. Ion pump using cylindrically symmetric spindle magnetic field

    For all accelerators and many research and industries, excellent vacuum conditions are required and the highest possible pumping rates are necessary. For most applications the standard ion sputtering pump (ISP) meets these requirements and is optimal for financial point of view also. The physical principle of the ISP is well known and many companies manufacture variety of ISP. Most of them use dipole magnetic field produced by permanent magnet and electric dipole field between the electrodes in which tenuous plasma is created because of interaction of between the relatively fast electrons slow residual gas atoms. Performance of an ISP depends basically on the electron cloud density in between the titanium electrodes but in the available present configurations no consideration has been given to electron confinement which needs a mirror magnetic field. If this is incorporated it will make a robust ISP surely; furthermore, the requirement of constant feeding of high voltage to electrodes for supplying sufficient number of electrons will be reduced too. A study has been performed to create sufficient rotationally symmetric spindle magnetic field (SMF) with inherent presence of magnetic mirror effect to electron motion to confine them for longer time for enhancing the density of electron cloud between the electrodes. It will lessen the electric power feeding the electrodes and lengthen their life-time. Construction of further compact and robust ISP is envisaged herein. The field simulation using the commercially available permanent magnet together with simulation of electron motion in such field will be presented and discussed in the paper.

  13. Ion pump using cylindrically symmetric spindle magnetic field

    Rashid, M. H.


    For all accelerators and many research and industries, excellent vacuum conditions are required and the highest possible pumping rates are necessary. For most applications the standard ion sputtering pump (ISP) meets these requirements and is optimal for financial point of view also. The physical principle of the ISP is well known and many companies manufacture variety of ISP. Most of them use dipole magnetic field produced by permanent magnet and electric dipole field between the electrodes in which tenuous plasma is created because of interaction of between the relatively fast electrons slow residual gas atoms. Performance of an ISP depends basically on the electron cloud density in between the titanium electrodes but in the available present configurations no consideration has been given to electron confinement which needs a mirror magnetic field. If this is incorporated it will make a robust ISP surely; furthermore, the requirement of constant feeding of high voltage to electrodes for supplying sufficient number of electrons will be reduced too. A study has been performed to create sufficient rotationally symmetric spindle magnetic field (SMF) with inherent presence of magnetic mirror effect to electron motion to confine them for longer time for enhancing the density of electron cloud between the electrodes. It will lessen the electric power feeding the electrodes and lengthen their life-time. Construction of further compact and robust ISP is envisaged herein. The field simulation using the commercially available permanent magnet together with simulation of electron motion in such field will be presented and discussed in the paper.

  14. Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase.

    Bokros, Michael; Gravenmier, Curtis; Jin, Fengzhi; Richmond, Daniel; Wang, Yanchang


    The spindle assembly checkpoint (SAC) monitors chromosome attachment defects, and the assembly of SAC proteins at kinetochores is essential for its activation, but the SAC disassembly process remains unknown. We found that deletion of a 14-3-3 protein, Bmh1, or hyperactivation of Cdc14 early anaphase release (FEAR) allows premature SAC silencing in budding yeast, which depends on a kinetochore protein Fin1 that forms a complex with protein phosphatase PP1. Previous works suggest that FEAR-dependent Fin1 dephosphorylation promotes Bmh1-Fin1 dissociation, which enables kinetochore recruitment of Fin1-PP1. We found persistent kinetochore association of SAC protein Bub1 in fin1Δ mutants after anaphase entry. Therefore, we revealed a mechanism that clears SAC proteins from kinetochores. After anaphase entry, FEAR activation promotes kinetochore enrichment of Fin1-PP1, resulting in SAC disassembly at kinetochores. This mechanism is required for efficient SAC silencing after SAC is challenged, and untimely Fin1-kinetochore association causes premature SAC silencing and chromosome missegregation. PMID:26832405

  15. The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac.

    Juan Cabello


    Full Text Available Wnt signalling pathways have extremely diverse functions in animals, including induction of cell fates or tumours, guidance of cell movements during gastrulation, and the induction of cell polarity. Wnt can induce polar changes in cellular morphology by a remodelling of the cytoskeleton. However, how activation of the Frizzled receptor induces cytoskeleton rearrangement is not well understood. We show, by an in depth 4-D microscopy analysis, that the Caenorhabditis elegans Wnt pathway signals to CED-10/Rac via two separate branches to regulate modulation of the cytoskeleton in different cellular situations. Apoptotic cell clearance and migration of the distal tip cell require the MOM-5/Fz receptor, GSK-3 kinase, and APC/APR-1, which activate the CED-2/5/12 branch of the engulfment machinery. MOM-5 (Frizzled thus can function as an engulfment receptor in C. elegans. Our epistatic analyses also suggest that the two partially redundant signalling pathways defined earlier for engulfment may act in a single pathway in early embryos. By contrast, rearrangement of mitotic spindles requires the MOM-5/Fz receptor, GSK-3 kinase, and beta-catenins, but not the downstream factors LIT-1/NLK or POP-1/Tcf. Taken together, our results indicate that in multiple developmental processes, CED-10/Rac can link polar signals mediated by the Wnt pathway to rearrangements of the cytoskeleton.

  16. Motion Track Modeling and Analysis of Belt Spindle under Combined Effects of Bending Moment-Torque-Thermal Deformation

    齐向阳; 高卫国; 刘腾; 张大卫


    The motion track of belt spindle is important for the radial error of belt spindle. An analytical modeling method for the motion track of belt spindle under the combined effects of bending moment-torque-thermal deforma-tion is proposed in this paper. Three running phases of belt spindle have been analyzed and modeled:the start-up phase with leaping change due to the change in force and bending moment, the accelerating phase with axis deflection, and the constant speed phase with axis regression because of the combined effects of bending moment-torque-thermal de-formation. The simulation and test were completed on the belt spindle of SKVM850 machine tool, which illustrates the variation law of the radial error of belt spindle during the whole running phases.

  17. Automotic Recognition of Sleep Spindles Based on Two-Stage Classifier with Artificial Neural Networks and Support Vector Machines

    MohammadHoseyn Khaksar; Amin Golrou; Saeed Rahati-Ghuchani


    Sleep spindles are one of the most important transient waveforms found in the sleep EEG signal. Here, we introduce a two-stage procedure based on artificial neural networks for the automatic recognition of sleep spindles (SS) in a 19-channel electroencephalographic signal. In the first stage, a pre-processing perception is used for enhancing overall detection and also reducing computation time. In the second stage, the selected Sleep spindles (SS), classified with neural network post-classifi...

  18. Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1.

    Ito, Daisuke; Saito, Yu; Matsumoto, Tomohiro


    The spindle checkpoint delays the onset of anaphase until all of the chromosomes properly achieve bipolar attachment to the spindle. It has been shown that unattached kinetochores are the site that emits a signal for activation of the checkpoint. Although the components of the checkpoint such as Bub1, Mad1 and Mad2 selectively accumulate at unattached kinetochores, the answer to how they recognize unattached kinetochores has remained elusive. Mps1 pombe homolog (Mph1) kinase has been shown to function upstream of most of the components of the checkpoint and thus it is thought to recognize unattached kinetochores by itself and recruit other components. In this study we have expressed a fusion protein of Mph1 and Ndc80 (a kinetochore protein of the outer plate) and shown that the fusion protein arrests cell cycle progression in a spindle-checkpoint\\x{2013}dependent manner in fission yeast. When expression of Mad2 is turned off, the cells grow normally with Mph1 constitutively localized at centromeres/kinetochores. Under this condition, Bub1 can be found with Mph1 throughout the cell cycle, indicating that localization of Mph1 at centromeres/kinetochores is sufficient to recruit Bub1. In contrast, Mad1 is found to transiently localize at kinetochores, which are presumably unattached to the spindle, but soon it dissociates from kinetochores. We propose that Mph1 is a sufficient marker for recruitment of Bub1. Mad1, in contrast, requires an additional condition/component for stable association with kinetochores. PMID:22184248

  19. When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

    David Gisselsson

    Full Text Available BACKGROUND: Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally. PRINCIPAL FINDINGS: Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells. CONCLUSION: The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient

  20. Accuracy analysis and design of A3 parallel spindle head

    Ni, Yanbing; Zhang, Biao; Sun, Yupeng; Zhang, Yuan


    As functional components of machine tools, parallel mechanisms are widely used in high efficiency machining of aviation components, and accuracy is one of the critical technical indexes. Lots of researchers have focused on the accuracy problem of parallel mechanisms, but in terms of controlling the errors and improving the accuracy in the stage of design and manufacturing, further efforts are required. Aiming at the accuracy design of a 3-DOF parallel spindle head(A3 head), its error model, sensitivity analysis and tolerance allocation are investigated. Based on the inverse kinematic analysis, the error model of A3 head is established by using the first-order perturbation theory and vector chain method. According to the mapping property of motion and constraint Jacobian matrix, the compensatable and uncompensatable error sources which affect the accuracy in the end-effector are separated. Furthermore, sensitivity analysis is performed on the uncompensatable error sources. The sensitivity probabilistic model is established and the global sensitivity index is proposed to analyze the influence of the uncompensatable error sources on the accuracy in the end-effector of the mechanism. The results show that orientation error sources have bigger effect on the accuracy in the end-effector. Based upon the sensitivity analysis results, the tolerance design is converted into the issue of nonlinearly constrained optimization with the manufacturing cost minimum being the optimization objective. By utilizing the genetic algorithm, the allocation of the tolerances on each component is finally determined. According to the tolerance allocation results, the tolerance ranges of ten kinds of geometric error sources are obtained. These research achievements can provide fundamental guidelines for component manufacturing and assembly of this kind of parallel mechanisms.

  1. NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

    Seldin, Lindsey; Muroyama, Andrew; Lechler, Terry


    Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures. DOI: PMID:26765568

  2. NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures.

    Seldin, Lindsey; Muroyama, Andrew; Lechler, Terry


    Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA's MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures. PMID:26765568

  3. Simulating ensembles of nonlinear continuous time dynamical systems via active ultra wideband wireless network

    Dmitriev, Alexander S.; Yemelyanov, Ruslan Yu.; Gerasimov, Mark Yu.; Itskov, Vadim V.


    The paper deals with a new multi-element processor platform assigned for modelling the behaviour of interacting dynamical systems, i.e., active wireless network. Experimentally, this ensemble is implemented in an active network, the active nodes of which include direct chaotic transceivers and special actuator boards containing microcontrollers for modelling the dynamical systems and an information display unit (colored LEDs). The modelling technique and experimental results are described and analyzed.

  4. Augmin shapes the anaphase spindle for efficient cytokinetic furrow ingression and abscission.

    Uehara, Ryota; Kamasaki, Tomoko; Hiruma, Shota; Poser, Ina; Yoda, Kinya; Yajima, Junichiro; Gerlich, Daniel W; Goshima, Gohta


    During anaphase, distinct populations of microtubules (MTs) form by either centrosome-dependent or augmin-dependent nucleation. It remains largely unknown whether these different MT populations contribute distinct functions to cytokinesis. Here we show that augmin-dependent MTs are required for the progression of both furrow ingression and abscission. Augmin depletion reduced the accumulation of anillin, a contractile ring regulator at the cell equator, yet centrosomal MTs were sufficient to mediate RhoA activation at the furrow. This defect in contractile ring organization, combined with incomplete spindle pole separation during anaphase, led to impaired furrow ingression. During the late stages of cytokinesis, astral MTs formed bundles in the intercellular bridge, but these failed to assemble a focused midbody structure and did not establish tight linkage to the plasma membrane, resulting in furrow regression. Thus augmin-dependent acentrosomal MTs and centrosomal MTs contribute to nonredundant targeting mechanisms of different cytokinesis factors, which are required for the formation of a functional contractile ring and midbody. PMID:26764096

  5. The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells

    Swapna Kollu


    Full Text Available To ensure accurate genomic segregation, cells evolved the spindle assembly checkpoint (SAC, whose role in adult stem cells remains unknown. Inducible perturbation of a SAC kinase, Mps1, and its downstream effector, Mad2, in skeletal muscle stem cells shows the SAC to be critical for normal muscle growth, repair, and self-renewal of the stem cell pool. SAC-deficient muscle stem cells arrest in G1 phase of the cell cycle with elevated aneuploidy, resisting differentiation even under inductive conditions. p21CIP1 is responsible for these SAC-deficient phenotypes. Despite aneuploidy’s correlation with aging, we find that aged proliferating muscle stem cells display robust SAC activity without elevated aneuploidy. Thus, muscle stem cells have a two-step mechanism to safeguard their genomic integrity. The SAC prevents chromosome missegregation and, if it fails, p21CIP1-dependent G1 arrest limits cellular propagation and tissue integration. These mechanisms ensure that muscle stem cells with compromised genomes do not contribute to tissue homeostasis.

  6. Characterization of a tomato protein kinase gene induced by infection by Potato spindle tuber viroid.

    Hammond, R W; Zhao, Y


    Viroids--covalently closed, circular RNA molecules in the size range of 250 to 450 nucleotides-are the smallest known infectious agents and cause a number of diseases of crop plants. Viroids do not encode proteins and replicate within the nucleus without a helper virus. In many cases, viroid infection results in symptoms of stunting, epinasty, and vein clearing. In our study of the molecular basis of the response of tomato cv. Rutgers to infection by Potato spindle tuber viroid (PSTVd), we have identified a specific protein kinase gene, pkv, that is transcriptionally activated in plants infected with either the intermediate or severe strain of PSTVd, at a lower level in plants inoculated with a mild strain, and not detectable in mock-inoculated plants. A full-length copy of the gene encoding the 55-kDa PKV (protein kinase viroid)-induced protein has been isolated and sequence analysis revealed significant homologies to cyclic nucleotide-dependent protein kinases. Although the sequence motifs in the catalytic domain suggest that it is a serine/threonine protein kinase, the recombinant PKV protein autophosphorylates in vitro on serine and tyrosine residues, suggesting that it is a putative member of the class of dual-specificity protein kinases. PMID:10975647

  7. Multi-Day Activity Scheduling Reactions to Planned Activities and Future Events in a Dynamic Model of Activity-Travel Behavior

    Nijland, L.; Arentze, T.; Timmermans, H.


    Modeling multi-day planning has received scarce attention in activity-based transport demand modeling so far. However, new dynamic activity-based approaches are being developed at the current moment. The frequency and inflexibility of planned activities and events in activity schedules of individual

  8. Active Control of Solar Array Dynamics During Spacecraft Maneuvers

    Ross, Brant A.; Woo, Nelson; Kraft, Thomas G.; Blandino, Joseph R.


    Recent NASA mission plans require spacecraft to undergo potentially significant maneuvers (or dynamic loading events) with large solar arrays deployed. Therefore there is an increased need to understand and possibly control the nonlinear dynamics in the spacecraft system during such maneuvers. The development of a nonlinear controller is described. The utility of using a nonlinear controller to reduce forces and motion in a solar array wing during a loading event is demonstrated. The result is dramatic reductions in system forces and motion during a 10 second loading event. A motion curve derived from the simulation with the closed loop controller is used to obtain similar benefits with a simpler motion control approach.

  9. Spindle formation and microtubule organization during first division in reconstructed rat embryos produced by somatic cell nuclear transfer.

    Tomioka, Ikuo; Mizutani, Eiji; Yoshida, Tomoyuki; Sugawara, Atsushi; Inai, Kentaro; Sasada, Hiroshi; Sato, Eimei


    The present study was conducted to demonstrate the spindle formation and behavior of chromosomes and microtubules during first division in reconstructed rat embryos produced by somatic cell nuclear transfer (SCNT) with cumulus cell nuclei. To demonstrate the effect of oocyte aging after ovulation on the cleavage of SCNT embryos, micromanipulation was carried out 11, 15 and 18 h after injection of hCG. SCNT oocytes were activated by incubation in culture medium supplemented with 5 microM ionomycin for 5 min followed by treatment with 2 mM 6-dimethylaminopurine (6-DMAP) in mR1ECM for 2-3 h. For immunocytochemical observation, the SCNT embryos were incubated with monoclonal anti-alpha-tubulin antibody and then fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse IgG. Cleavage rates were significantly higher for oocytes collected after 15 and 18 h rather than for those collected 11 h after injection of hCG (56 and 53%, respectively vs. 28%; P<0.05). Premature chromosome condensation occurred before activation of the SCNT oocytes, but adequate spindle formation was only rarely observed. The distribution of microtubules in SCNT embryos after activation was different from those of fertilized and parthenogenic oocytes, i.e., a dense microtubule organization shaped like a ring was observed. Eighteen to 20 h post-activation, most SCNT embryos were in the 2-cell stage, but no nucleoli were clearly visible, which was quite different from the fertilized oocytes. In addition, first division with and without small cellular bodies containing DNA was observed in the rat SCNT embryos in some cases. The present study suggests that reorganization of transferred nuclei in rat SCNT embryos may be inadequate in terms of formation of the mitotic assembly and nucleolar reorganization. PMID:17446658

  10. Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

    Brand Andrea H


    Full Text Available Abstract Background The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. Results Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. Conclusion We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

  11. Pins is not required for spindle orientation in the Drosophila wing disc.

    Bergstralh, Dan T; Lovegrove, Holly E; Kujawiak, Izabela; Dawney, Nicole S; Zhu, Jinwei; Cooper, Samantha; Zhang, Rongguang; St Johnston, Daniel


    In animal cells, mitotic spindles are oriented by the dynein/dynactin motor complex, which exerts a pulling force on astral microtubules. Dynein/dynactin localization depends on Mud/NUMA, which is typically recruited to the cortex by Pins/LGN. In Drosophila neuroblasts, the Inscuteable/Baz/Par-6/aPKC complex recruits Pins apically to induce vertical spindle orientation, whereas in epithelial cells Dlg recruits Pins laterally to orient the spindle horizontally. Here we investigate division orientation in the Drosophila imaginal wing disc epithelium. Live imaging reveals that spindle angles vary widely during prometaphase and metaphase, and therefore do not reliably predict division orientation. This finding prompted us to re-examine mutants that have been reported to disrupt division orientation in this tissue. Loss of Mud misorients divisions, but Inscuteable expression and aPKC, dlg and pins mutants have no effect. Furthermore, Mud localizes to the apical-lateral cortex of the wing epithelium independently of both Pins and cell cycle stage. Thus, Pins is not required in the wing disc because there are parallel mechanisms for Mud localization and hence spindle orientation, making it a more robust system than in other epithelia. PMID:27287805

  12. Regulation of a Spindle Positioning Factor at Kinetochores by SUMO-Targeted Ubiquitin Ligases.

    Schweiggert, Jörg; Stevermann, Lea; Panigada, Davide; Kammerer, Daniel; Liakopoulos, Dimitris


    Correct function of the mitotic spindle requires balanced interplay of kinetochore and astral microtubules that mediate chromosome segregation and spindle positioning, respectively. Errors therein can cause severe defects ranging from aneuploidy to developmental disorders. Here, we describe a protein degradation pathway that functionally links astral microtubules to kinetochores via regulation of a microtubule-associated factor. We show that the yeast spindle positioning protein Kar9 localizes not only to astral but also to kinetochore microtubules, where it becomes targeted for proteasomal degradation by the SUMO-targeted ubiquitin ligases (STUbLs) Slx5-Slx8. Intriguingly, this process does not depend on preceding sumoylation of Kar9 but rather requires SUMO-dependent recruitment of STUbLs to kinetochores. Failure to degrade Kar9 leads to defects in both chromosome segregation and spindle positioning. We propose that kinetochores serve as platforms to recruit STUbLs in a SUMO-dependent manner in order to ensure correct spindle function by regulating levels of microtubule-associated proteins. PMID:26906737

  13. Mitotic spindle asymmetry in rodents and primates:2D versus 3D measurement methodologies

    Delphine eDelaunay


    Full Text Available Recent data have uncovered that spindle size asymmetry (SSA is a key component of asymmetric cell division in the mouse cerebral cortex (Delaunay et al., 2014. In the present study we show that SSA also occurs during cortical progenitor divisions in the ventricular zone of the macaque cerebral cortex, pointing to a conserved mechanism in the mammalian lineage. Because SSA magnitude is smaller in cortical precursors than in invertebrate neuroblasts, the unambiguous demonstration of volume differences between the two half spindles is considered to require 3D reconstruction of the mitotic spindle (Delaunay et al., 2014. Although straightforward, the 3D analysis of SSA is time consuming, which is likely to hinder SSA identification and prevent further explorations of SSA related mechanisms in generating asymmetric cell division. We therefore set out to develop an alternative method for accurately measuring spindle asymmetry. Based on the mathematically demonstrated linear relationship between 2D and 3D analysis, we show that 2D assessment of spindle size in metaphase cells is as accurate and reliable as 3D reconstruction provided a specific procedure is applied. We have examined the experimental accuracy of the two methods by applying them to different sets of in vivo and in vitro biological data, including mouse and primate cortical precursors. Linear regression analysis demonstrates that the results from 2D and 3D reconstructions are equally powerful. We therefore provide a reliable and efficient technique to measure SSA in mammalian cells.

  14. MLL5 maintains spindle bipolarity by preventing aberrant cytosolic aggregation of PLK1.

    Zhao, Wei; Liu, Jie; Zhang, Xiaoming; Deng, Lih-Wen


    Faithful chromosome segregation with bipolar spindle formation is critical for the maintenance of genomic stability. Perturbation of this process often leads to severe mitotic failure, contributing to tumorigenesis. MLL5 has been demonstrated to play vital roles in cell cycle progression and the maintenance of genomic stability. Here, we identify a novel interaction between MLL5 and PLK1 in the cytosol that is crucial for sustaining spindle bipolarity during mitosis. Knockdown of MLL5 caused aberrant PLK1 aggregation that led to acentrosomal microtubule-organizing center (aMTOC) formation and subsequent spindle multipolarity. Further molecular studies revealed that the polo-box domain (PBD) of PLK1 interacted with a binding motif on MLL5 (Thr887-Ser888-Thr889), and this interaction was essential for spindle bipolarity. Overexpression of wild-type MLL5 was able to rescue PLK1 mislocalization and aMTOC formation in MLL5-KD cells, whereas MLL5 mutants incapable of interacting with the PBD failed to do so. We thus propose that MLL5 preserves spindle bipolarity through maintaining cytosolic PLK1 in a nonaggregated form. PMID:27002166

  15. Thermal Error Modelling of the Spindle Using Data Transformation and Adaptive Neurofuzzy Inference System

    Yanlei Li


    Full Text Available This paper proposes a new method for predicting spindle deformation based on temperature data. The method introduces the adaptive neurofuzzy inference system (ANFIS, which is a neurofuzzy modeling approach that integrates the kernel and geometrical transformations. By utilizing data transformation, the number of ANFIS rules can be effectively reduced and the predictive model structure can be simplified. To build the predictive model, we first map the original temperature data to a feature space with Gaussian kernels. We then process the mapped data with the geometrical transformation and make the data gather in the square region. Finally, the transformed data are used as input to train the ANFIS. A verification experiment is conducted to evaluate the performance of the proposed method. Six Pt100 thermal resistances are used to monitor the spindle temperature, and a laser displacement sensor is used to detect the spindle deformation. Experimental results show that the proposed method can precisely predict the spindle deformation and greatly improve the thermal performance of the spindle. Compared with back propagation (BP networks, the proposed method is more suitable for complex working conditions in practical applications.


    Hobbs, Joshua; Sutherland-Smith, James; Penninck, Dominique; Jennings, Samuel; Barber, Lisa; Barton, Bruce


    Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of gastrointestinal spindle cell tumor recognized with the increasing use of immunohistochemistry. To our knowledge, no imaging features have been described in immunostochemically confirmed canine GISTs. The objective of this retrospective, cross-sectional study was to describe ultrasonographic features of canine GISTs compared with other spindle cell tumors. Thirty-seven dogs with an ultrasonographically visible gastrointestinal mass and a histopathologic diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining was performed for retrieved tissue samples to further differentiate the tumor type and each sample was interpreted by a single veterinary pathologist. Ultrasonographic features recorded examined included mass echogenicity, homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and loss of wall layering, location, size, vascularity, and evidence of perforation or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were significantly more likely to be associated (P < 0.03) with abdominal effusion than other tumor types. There was overlap between the anatomical locations of all tumors types with the exception of the cecum where all eight tumors identified were GISTs. Besides location, there were no unique ultrasound features of GISTs that would allow distinction from other gastrointestinal spindle cell tumors. Similar to previous studies, GISTs appeared to be the most common spindle cell tumor associated with the cecum in our sample of dogs. The high frequency of abdominal effusion with GIST's was of unknown etiology could possibly have been due to septic peritonitis. PMID:25846814

  17. Individual firm and market dynamics of CSR activities

    Wirl, F.; Feichtinger, G.; Kort, P.M.


    This paper investigates how firms should plan corporate social responsibility (short CSR). This dynamic analysis starts with a firm's intertemporal optimization problem, and proceeds to analyze interactions with other firms, which are crucial: if CSR is profitable for firm A then it is most likely a

  18. Dynamic adsorption properties of xenon on activated carbons and their structure characterization

    Background: In recent years, adsorption of radioactive xenon by activated carbon has been increasingly applied to the treatment of off-gas in nuclear power project. Though pore structure of activated carbon has a great impact on its dynamic adsorption coefficients for xenon, the concerned research is rare. Purpose: It is very necessary to figure out the relationship between the pore structure and the dynamic adsorption coefficients for the purpose of the selection and development of activated carbon. Methods: In this study, the dynamic adsorption coefficients of xenon on four kinds of activated carbons were measured on a dynamic adsorption platform under the condition of 25℃, OMPa (gauge pressure). And these four kinds of activated carbons were characterized by nitrogen adsorption and SEM. Results: The results show that the activated carbon of JH12-16 with the specific surface area of 991.9 m2·g-1 has the largest xenon dynamic adsorption coefficient among these activated carbons. Conclusions: The dynamic adsorption coefficient of xenon on activated carbon doesn't increase with the specific surface area or the pore volume. The mesopore and macropore only play the role of passageway for xenon adsorption. The most suitable pore for xenon adsorption is the pore with the pore size ranged from 0.55 to 0.6 nm. (authors)

  19. Lexical Activation in Bilinguals' Speech Production Is Dynamic: How Language Ambiguous Words Can Affect Cross-Language Activation

    Hermans, Daan; Ormel, E.; van Besselaar, Ria; van Hell, Janet


    Is the bilingual language production system a dynamic system that can operate in different language activation states? Three experiments investigated to what extent cross-language phonological co-activation effects in language production are sensitive to the composition of the stimulus list. L1 Dutch-L2 English bilinguals decided whether or not a…

  20. Synchronous Twin Spindle Precision Machining System%同步双主轴精密加工系统

    张霖; 廖文和; 张志英; 赵义顺; 雷小宝; 涂芬芬


    介绍了自行研制的小型同步双主轴五轴联动精密加工系统,主体尺寸为680mm×620mm×400mm,主轴最高转速80 000 r/min,跳动量小于2μm.利用激光干涉仪测得定位精度为5μm;对直线运动轴伺服系统进行设计,经伺服环调节及性能试验,获得优良的动、静态控制性能.采用直径0.2μm的端铣刀进行平面微铣削加工,获得表面粗糙度值为215 nm.结果表明该系统充分具备微小零件的高效加工能力.%A miniaturized twin spindle precise machining system is mentioned for miniaturied parts. The main part of the equipment has a base size of 680 mm × 620 mm ×400 mm with a highest spindle speed of 80 000 r/min and its diameter run-out less than 2 μm. The positioning accuracy of micron is measured by a laser interferometer. And it describs the design of computerized numerical control (CNC) servo system of linear motion axis. The servo experiment results verify the excellent static and dynamic performance of the system. The machining tests include a plane with a surface roughness of 215 nm using a end milling cutter of ()0. 2 μm. The analytical results of these tests show that the system can fulfill the efficient machining of micro components.

  1. Computational Systems Biology Analysis of Cell Reprogramming and Activation Dynamics

    Fu, Yan


    In the past two decades, molecular cell biology has transitioned from a traditional descriptive science into a quantitative science that systematically measures cellular dynamics on different levels of genome, transcriptome and proteome. Along with this transition emerges the interdisciplinary field of systems biology, which aims to unravel complex interactions in biological systems through integrating experimental data into qualitative or quantitative models and computer simulations. In th...

  2. Dynamics of water molecules in the active-site cavity of human cytochromes P450

    Rydberg, Patrik; Rod, Thomas Holm; Olsen, Lars;


    We have studied the dynamics of water molecules in six crystal structures of four human cytochromes P450, 2A6, 2C8, 2C9, and 3A4, with molecular dynamics simulations. In the crystal structures, only a few water molecules are seen and the reported sizes of the active-site cavity vary a lot. In the...

  3. A Bipolar Spindle of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation

    Gayathri, P; Fujii, T; Møller-Jensen, Jakob;


    To ensure their stable inheritance by daughter cells during cell division, bacterial low copy-number plasmids make simple DNA segregating machines that use an elongating protein filament between sister plasmids. In the ParMRC system of Escherichia coli R1 plasmid, ParM, an actin-like protein, forms...... the spindle between ParRC complexes on sister plasmids. Using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture...... of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles....

  4. Sensory reinnervation of muscle spindles after repair of tibial nerve defects using autogenous vein grafts

    Youwang Pang; Qingnan Hong; Jinan Zheng


    Motor reinnervation after repair of tibial nerve defects using autologous vein grafts in rats has previously been reported, but sensory reinnervation after the same repair has not been fully investigated. In this study, partial sensory reinnervation of muscle spindles was observed after repair of 10-mm left tibial nerve defects using autologous vein grafts with end-to-end anasto-mosis in rats, and functional recovery was conifrmed by electrophysiological studies. There were no signiifcant differences in the number, size, or electrophysiological function of reinnervated muscle spindles between the two experimental groups. These ifndings suggest that repair of short nerve defects with autologous vein grafts provides comparable results to immediate end-to-end anastomosis in terms of sensory reinnervation of muscle spindles.

  5. High-Speed Spindle Fault Diagnosis with the Empirical Mode Decomposition and Multiscale Entropy Method

    Nan-Kai Hsieh


    Full Text Available The root mean square (RMS value of a vibration signal is an important indicator used to represent the amplitude of vibrations in evaluating the quality of high-speed spindles. However, RMS is unable to detect a number of common fault characteristics that occur prior to bearing failure. Extending the operational life and quality of spindles requires reliable fault diagnosis techniques for the analysis of vibration signals from three axes. This study used empirical mode decomposition to decompose signals into intrinsic mode functions containing a zero-crossing rate and energy to represent the characteristics of rotating elements. The MSE curve was then used to identify a number of characteristic defects. The purpose of this research was to obtain vibration signals along three axes with the aim of extending the operational life of devices included in the product line of an actual spindle manufacturing company.

  6. Dynamic structure of joint-action stimulus-response activity.

    MaryLauren Malone

    Full Text Available The mere presence of a co-actor can influence an individual's response behavior. For instance, a social Simon effect has been observed when two individuals perform a Go/No-Go response to one of two stimuli in the presence of each other, but not when they perform the same task alone. Such effects are argued to provide evidence that individuals co-represent the task goals and the to-be-performed actions of a co-actor. Motivated by the complex-systems approach, the present study was designed to investigate an alternative hypothesis--that such joint-action effects are due to a dynamical (time-evolving interpersonal coupling that operates to perturb the behavior of socially situated actors. To investigate this possibility, participants performed a standard Go/No-Go Simon task in joint and individual conditions. The dynamic structure of recorded reaction times was examined using fractal statistics and instantaneous cross-correlation. Consistent with our hypothesis that participants responding in a shared space would become behaviorally coupled, the analyses revealed that reaction times in the joint condition displayed decreased fractal structure (indicative of interpersonal perturbation processes modulating ongoing participant behavior compared to the individual condition, and were more correlated across a range of time-scales compared to the reaction times of pseudo-pair controls. Collectively, the findings imply that dynamic processes might underlie social stimulus-response compatibility effects and shape joint cognitive processes in general.

  7. Probing CENP-E function in chromosome dynamics using small molecule inhibitor syntelin

    Xia Ding; Tongge Zhu; Jiancun Zhang; Zhen Dou; Xuebiao Yao; Feng Yan; Phil Yao; Zhihong Yang; Weihong Wan; Xiwei Wang; Jing Liu; Xinjiao Gao; Ariane Abrieu


    @@ Dear Editor, Chromosome movements during mitosis are orchestrated primarily by the interaction of spindle microtubules with the kinetochore [1], the site for attachment of spindle microtubules to the centromere. The kinetochore has an active function in chromosomal segregation through microtubule-based motors located at or near it [1-2].


    Mahmut ÖZER


    Full Text Available In this paper, alternative equations for dynamics of ionic channel activation and inactivation gates are proposed based on the path probability method. Dynamic behavior of a voltage-gated ionic channel is modeled by the conventional Hodgkin-Huxley (H-H mathematical formalism. In that model, conductance of the channel is defined in terms of activation and inactivation gates. Dynamics of the activation and inactivation gates is modeled by first-order differential equations dependent on the gate variable and the membrane potential. In the new approach proposed in this study, dynamic behavior of activation and inactivation gates is modeled by a firstorder differential equation dependent on internal energy and membrane potential by using the path probability method which is widely used in statistical physics. The new model doesn't require the time constant and steadystate values which are used explicitly in the H-H model. The numerical results show validity of the proposed method.

  9. Modeling the dynamics of a tracer particle in an elastic active gel.

    Ben-Isaac, E; Fodor, É; Visco, P; van Wijland, F; Gov, Nir S


    The internal dynamics of active gels both in artificial (in vitro) model systems and inside the cytoskeleton of living cells has been extensively studied with experiments of recent years. These dynamics are probed using tracer particles embedded in the network of biopolymers together with molecular motors, and distinct nonthermal behavior is observed. We present a theoretical model of the dynamics of a trapped active particle, which allows us to quantify the deviations from equilibrium behavior, using both analytic and numerical calculations. We map the different regimes of dynamics in this system and highlight the different manifestations of activity: breakdown of the virial theorem and equipartition, different elasticity-dependent "effective temperatures," and distinct non-Gaussian distributions. Our results shed light on puzzling observations in active gel experiments and provide physical interpretation of existing observations, as well as predictions for future studies. PMID:26274211

  10. Nonequilibrium structure and dynamics in a microscopic model of thin-film active gels

    Head, D.A.; Briels, W.J.; Gompper, G.


    In the presence of adenosine triphosphate, molecular motors generate active force dipoles that drive suspensions of protein filaments far from thermodynamic equilibrium, leading to exotic dynamics and pattern formation. Microscopic modeling can help to quantify the relationship between individual mo

  11. Pulmonary sclerosing hemangioma presenting with dense spindle stroma cells: a potential diagnostic pitfall

    Lin Xu-Yong


    Full Text Available Abstract Pulmonary sclerosing hemangioma (PSH is an uncommon pulmonary tumor. Histologically, PSH typically consists of two types of cells, surface cuboidal cells and polygonal cells, four architectural patterns including papillary, sclerotic, solid, and hemorrhagic. Herein, we present a case of PSH in a 59-year-old Chinese female. The tumor was predominantly composed of solid area presenting with diffuse spindle cells rather than polygonal cells. Focally, classical papillary and sclerotic area could be seen. Immunohistochemical staining showed that the spindle cells were positive for TTF-1, EMA, Actin(SM and Vimentin, and negative for cytokeratin, cytokeratin7, cytokeratin5/6, surfactant apoprotein A, surfactant apoprotein B, CD34, CD99, S-100, HMB45, Desmin, Synaptophysin, CD56, ALK and Calretinin. The immunophenotype of the dense spindle cells in this case was similar to that of the polygonal cells, and thus the spindle cells may be the variants of polygonal cells. Based on morphologic features and the immunohistochemical profile, the tumor was diagnosed as a PSH. The significance of spindle cells change is unclear for us. To our knowledge, this is the first reported case of PSH showing dense spindle cells in solid area. This case represents a potential diagnostic pitfall, as it may be misdiagnosed as a mesenchymal tumor such as inflammatory myofibroblastic tumor, synovial sarcoma, solitary fibrous tumor, leiomyoma, or even mesothelioma, especially if the specimen is limited or from fine- needle aspiration. Virtual slides The virtual slide(s for this article can be found here:

  12. Tourist activated networks: Implications for dynamic packaging systems in tourism

    Zach, Florian; Gretzel, Ulrike; Fesenmaier, Daniel R.


    structure. The results indicate that the tourist activated network for the destination is rather sparse and that there are clearly differences in core and peripheral nodes. The findings illustrate the structure of a tourist activated network and provide implications for technology design and tourism...

  13. Energy landscape and dynamics of brain activity during human bistable perception.

    Watanabe, Takamitsu; Masuda, Naoki; Magumi, Fukuda; Kanai, Ryota; Rees, Geraint


    Individual differences in the structure of parietal and prefrontal cortex predict the stability of bistable visual perception. However, the mechanisms linking such individual differences in brain structures to behavior remain elusive. Here we demonstrate a systematic relationship between the dynamics of brain activity, cortical structure and behavior underpinning bistable perception. Using fMRI inhumans, we find that the activity dynamics during bistable perception are well described as fluct...

  14. Semi-Active Control of the Sway Dynamics for Elevator Ropes

    Benosman, Mouhacine


    In this work we study the problem of rope sway dynamics control for elevator systems. We choose to actuate the system with a semi-active damper mounted on the top of the elevator car. We propose nonlinear controllers based on Lyapunov theory, to actuate the semi-active damper and stabilize the rope sway dynamics. We study the stability of the proposed controllers, and test their performances on a numerical example.

  15. Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis

    Østergaard, Mikkel; Lorenzen, I; Henriksen, O


    Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We exa...... synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints....

  16. Feasibility of Applying Active Lubrication to Dynamically Loaded Fluid Film Bearings

    Estupinan, Edgar Alberto; Santos, Ilmar


    The feasibility of modifying the dynamics of the thin fluid films of dynamically loaded journal bearings, using different strategies of active lubrication is studied in this work. A significant reduction in the vibration levels, wear and power friction losses, is expected. Particularly, the focus...... of this study is on the analysis of main crankshaft bearings, where the conventional hydrodynamic lubrication is modified by injecting oil at actively controllable pressures, through orifices circumferentially located along the bearing surface....

  17. Age-Related Shifts in Brain Activity Dynamics during Task Switching

    Jimura, Koji; Braver, Todd S.


    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and ...

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

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


    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 automati

  19. Validation of a novel automatic sleep spindle detector with high performance during sleep in middle aged subjects

    Wendt, Sabrina Lyngbye; Christensen, Julie A. E.; Kempfner, Jacob;


    Many of the automatic sleep spindle detectors currently used to analyze sleep EEG are either validated on young subjects or not validated thoroughly. The purpose of this study is to develop and validate a fast and reliable sleep spindle detector with high performance in middle aged subjects. An...

  20. Helix 11 Dynamics is Critical for Constitutive Androstane Receptor Activity

    Wright, Edward; Busby, Scott A.; Wisecarver, Sarah; Vincent, Jeremy; Griffin, Patrick R.; Fernandez, Elias J.


    The constitutive androstane receptor (CAR) transactivation can occur in the absence of exogenous ligand and this activity is enhanced by agonists TCPOBOP and meclizine. We use biophysical and cell-based assays to show that increased activity of CAR(TCPOBOP) relative to CAR(meclizine) corresponds to a higher affinity of CAR(TCPOBOP) for the steroid receptor coactivator-1. Additionally, steady-state fluorescence spectra suggest conformational differences between CAR(TCPOBOP):RXR and CAR(meclizi...

  1. Diversity and dynamics of Archaea in an activated sludge wastewater treatment plant

    Fredriksson, Nils Johan; Hermansson, Malte; Wilén, Britt-Marie


    Background The activated sludge process is one of the most widely used methods for treatment of wastewater and the microbial community composition in the sludge is important for the process operation. While the bacterial communities have been characterized in various activated sludge systems little is known about archaeal communities in activated sludge. The diversity and dynamics of the Archaea community in a full-scale activated sludge wastewater treatment plant were investigated by fluores...

  2. Contributions to the dynamics of helicopters with active rotor controls

    Malpica, Carlos A.

    This dissertation presents an aeromechanical closed loop stability and response analysis of a hingeless rotor helicopter with a Higher Harmonic Control (HHC) system for vibration reduction. The analysis includes the rigid body dynamics of the helicopter and blade flexibility. The gain matrix is assumed to be fixed and computed off-line. The discrete elements of the HHC control loop are rigorously modeled, including the presence of two different time scales in the loop. By also formulating the coupled rotor-fuselage dynamics in discrete form, the entire coupled helicopter-HHC system could be rigorously modeled as a discrete system. The effect of the periodicity of the equations of motion is rigorously taken into account by converting the system into an equivalent system with constant coefficients and identical stability properties using a time lifting technique. The most important conclusion of the present study is that the discrete elements in the HHC loop must be modeled in any HHC analysis. Not doing so is unconservative. For the helicopter configuration and HHC structure used in this study, an approximate continuous modeling of the HHC system indicates that the closed loop, coupled helicopter-HHC system remains stable for optimal feedback control configurations which the more rigorous discrete analysis shows can result in closed loop instabilities. The HHC gains must be reduced to account for the loss of gain margin brought about by the discrete elements. Other conclusions of the study are: (i) the HHC is effective in quickly reducing vibrations, at least at its design condition, although the time constants associated with the closed loop transient response indicate closed loop bandwidth to be 1 rad/sec on average, thus overlapping with FCS or pilot bandwidths, and raising the issue of potential interactions; (ii) a linearized model of helicopter dynamics is adequate for HHC design, as long as the periodicity of the system is correctly taken into account, i

  3. Analysis on Dynamic Performance for Active Magnetic Bearing—Rotor System

    YANHui-yan; WANGXi-ping; 等


    In the application of active magnetic bearings(AMB),one of the key problems to be solved is the safety and stabiltiy in the sense of rotor dynamics,The project related to the present paper deals with the method for analyzing bearing rotor systems with high rotation speed and specially supported by active magnetic bearings,and studies its rotor dynamics performance,including calculation of the natural frequencies with their distribution characteristics,and the critical speeds of the of the targets of this project is to formulate a theory and method valid for the analysis of the dynamic performance of the active magntic bearing-rotor systemby combining the traditional theory and method of rotor dynamics with the analytical theory and design method based on modern control theory of the AMB system.

  4. Stage-independent, single lead EEG sleep spindle detection using the continuous wavelet transform and local weighted smoothing

    Athanasios eTsanas


    Full Text Available Sleep spindles are critical in characterizing sleep and have been associated with cognitive function and pathophysiological assessment. Typically, their detection relies on the subjective and time-consuming visual examination of electroencephalogram (EEG signal(s by experts, and has led to large inter-rater variability as a result of poor definition of sleep spindle characteristics. Hitherto, many algorithmic spindle detectors inherently make signal stationarity assumptions (e.g. Fourier transform-based approaches which are inappropriate for EEG signals, and frequently rely on additional information which may not be readily available in many practical settings (e.g. more than one EEG channels, or prior hypnogram assessment. This study proposes a novel signal processing methodology relying solely on a single EEG channel, and provides objective, accurate means towards probabilistically assessing the presence of sleep spindles in EEG signals. We use the intuitively appealing continuous wavelet transform (CWT with a Morlet basis function, identifying regions of interest where the power of the CWT coefficients corresponding to the frequencies of spindles (11-16 Hz is large. The potential for assessing the signal segment as a spindle is refined using local weighted smoothing techniques. We evaluate our findings on two databases: the MASS database comprising 19 healthy controls and the DREAMS sleep spindle database comprising eight participants diagnosed with various sleep pathologies. We demonstrate that we can replicate the experts’ sleep spindles assessment accurately in both databases (MASS database: sensitivity: 84%, specificity: 90%, false discovery rate 83%, DREAMS database: sensitivity: 76%, specificity: 92%, false discovery rate: 67%, outperforming six competing automatic sleep spindle detection algorithms in terms of correctly replicating the experts’ assessment of detected spindles.

  5. Double Modelling of the Dynamic of Activities in Rural Municipalities

    Ternes, S; Huet, S; Deffuant, G


    Land use choices and activity prevalence in a selected territory are determined by individual preferences constrained by the characteristic of the analysed zone: population density, soil properties, urbanization level and other similar factors can drive individuals to make different kind of decisions about their occupations. Different approaches can be used to describe land use change, occupation prevalence and their reciprocal inter-relation. In this paper we describe two different kinds of approaches: an agent based model, centred on individual choices and an aggregated model describing the evolution of activity prevalence in terms of coupled differential equation. We use and we compare the two models to analyse the effect of territorial constraints, like the lack of employment in determined sectors, on the possible activity prevalence scenarios.

  6. Kink waves in an active region dynamic fibril

    Pietarila, A; Hirzberger, J; Solanki, S K


    We present high spatial and temporal resolution Ca II 8542 observations of a kink wave in an on-disk chromospheric active region fibril. The properties of the wave are similar to those observed in off-limb spicules. From the observed phase and period of the wave we determine a lower limit for the field strength in the chromospheric active region fibril located at the edge of a sunspot to be a few hundred Gauss. We find indications that the event was triggered by a small-scale reconnection event higher up in the atmosphere.

  7. The Globalization of Value chain activities, Knowledge dynamics, and Innovation

    Park, Eunkyung

    Firms are increasingly relocating diverse activities in the value chain abroad to reap the locational advantage available in other countries. One of the issues raised in this context is that, as global operations can function as channels for knowledge flows, the involved firms and locations may...... involved regions and countries. The purpose of this thesis is to study these issues with a broad research question, “What implications does the globalization of value chain activities have on innovation in firms and locations?” Four articles and a case study included in the thesis present empirical results...

  8. F-actin asymmetry and the endoplasmic reticulum-associated TCC-1 protein contribute to stereotypic spindle movements in the Caenorhabditis elegans embryo

    Berends, C.W.H.; Muñoz, J.; Portegijs, V.C.; Schmidt, R.; Grigoriev, I.S.; Boxem, M.; Akhmanova, A.S.; Heck, A.J.R.; van den Heuvel, S.


    The microtubule spindle apparatus dictates the plane of cell cleavage in animal cells. During development, dividing cells control the position of the spindle to determine the size, location, and fate of daughter cells. Spindle positioning depends on pulling forces that act between the cell periphery

  9. Modeling Temporal Activity Patterns in Dynamic Social Networks

    Raghavan, Vasanthan; Galstyan, Aram; Tartakovsky, Alexander G


    The focus of this work is on developing probabilistic models for user activity in social networks by incorporating the social network influence as perceived by the user. For this, we propose a coupled Hidden Markov Model, where each user's activity evolves according to a Markov chain with a hidden state that is influenced by the collective activity of the friends of the user. We develop generalized Baum-Welch and Viterbi algorithms for model parameter learning and state estimation for the proposed framework. We then validate the proposed model using a significant corpus of user activity on Twitter. Our numerical studies show that with sufficient observations to ensure accurate model learning, the proposed framework explains the observed data better than either a renewal process-based model or a conventional uncoupled Hidden Markov Model. We also demonstrate the utility of the proposed approach in predicting the time to the next tweet. Finally, clustering in the model parameter space is shown to result in dist...

  10. Object texture recognition by dynamic tactile sensing using active exploration

    Drimus, Alin; Børlum Petersen, Mikkel; Bilberg, Arne

    For both humans and robots, tactile sensing is important for interaction with the environment: it is the core sensing used for exploration and manipulation of objects. In this paper, we present a method for determining object texture by active exploration with a robotic fingertip equipped with a...

  11. Dynamic Precursors of Flares in Active Region NOAA 10486

    Korsos, M B; Baranyi, T; Ludmany, A


    Four different methods are applied here to study the precursors of flare activity in the Active Region NOAA 10486. Two approaches track the temporal behaviour of suitably chosen features (one, the weighted horizontal gradient WGM, is generalised form the horizontal gradient of the magnetic field, GM; another is the sum of the horizontal gradient of the magnetic field, GS, for all sunspot pairs). WGM is a photospheric indicator that is a proxy measure of magnetic non-potentiality of a specific area of the active region, i.e. it captures the temporal variation of the weighted horizontal gradient of magnetic flux summed up for the region where opposite magnetic polarities are highly mixed. The third one, referred to as the separateness parameter, S(lf), considers the overall morphology. Further, GS and S(lf) are photospheric newly defined quick-look indicators of the polarity mix of the entire active region. The fourth method is tracking the temporal variation of small x-ray flares, their times of succession and...

  12. Dynamic Precursors of Flares in Active Region NOAA 10486

    M. B. Korsós; N. Gyenge; T. Baranyi; A. Ludmány


    Four different methods are applied here to study the precursors of flare activity in the Active Region NOAA 10486. Two approaches track the temporal behaviour of suitably chosen features (one, the weighted horizontal gradient WGM, is the generalized form of the horizontal gradient of the magnetic field, GM; the other is the sum of the horizontal gradient of the magnetic field, GS, for all sunspot pairs). WGM is a photospheric indicator, that is a proxy measure of magnetic non-potentiality of a specific area of the active region, i.e., it captures the temporal variation of the weighted horizontal gradient of magnetic flux summed up for the region where opposite magnetic polarities are highly mixed. The third one, referred to as the separateness parameter, Sl−f, considers the overall morphology. Further, GS and Sl−f are photospheric, newly defined quick-look indicators of the polarity mix of the entire active region. The fourth method is tracking the temporal variation of small X-ray flares, their times of succession and their energies observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager instrument. All approaches yield specific pre-cursory signatures for the imminence of flares.

  13. Spindle trees (Euonymus japonica Thunb.) growing in a polluted environment are less sensitive to gamma irradiation

    Kim, J. K.; Cha, M.; Mukherjee, A.; Wilhelmová, Naděžda


    Roč. 11, č. 4 (2013), s. 233-243. ISSN 2322-3243 Institutional research plan: CEZ:AV0Z50380511 Keywords : Spindle tree * oxidative stress * ionizing radiation Subject RIV: EF - Botanics

  14. Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation.

    Carminati, Manuel; Gallini, Sara; Pirovano, Laura; Alfieri, Andrea; Bisi, Sara; Mapelli, Marina


    Polarized epithelia form by oriented cell divisions in which the mitotic spindle aligns parallel to the epithelial plane. To orient the mitotic spindle, cortical cues trigger the recruitment of NuMA-dynein-based motors, which pull on astral microtubules via the protein LGN. We demonstrate that the junctional protein Afadin is required for spindle orientation and correct epithelial morphogenesis of Caco-2 cysts. Molecularly, Afadin binds directly and concomitantly to F-actin and to LGN. We determined the crystallographic structure of human Afadin in complex with LGN and show that it resembles the LGN-NuMA complex. In mitosis, Afadin is necessary for cortical accumulation of LGN and NuMA above the spindle poles, in an F-actin-dependent manner. Collectively, our results depict Afadin as a molecular hub governing the enrichment of LGN and NuMA at the cortex. To our knowledge, Afadin is the first-described mechanical anchor between dynein and cortical F-actin. PMID:26751642

  15. No Reduction of Spindle Neuron Number in Frontoinsular Cortex in Autism

    Kennedy, Daniel P.; Semendeferi, Katerina; Courchesne, Eric


    It has been suggested that spindle neurons, an evolutionarily unique type of neuron, might be involved in higher-order social, emotional, and cognitive functions. As such, it was hypothesized that these neurons may be particularly important to the pathophysiology of autism, a disease characterized in part by disruption of higher-order social and…

  16. The effect of magnesium on mitotic spindle formation in Schizosaccharomyces pombe.

    Uz, Gulsen; Sarikaya, Aysegul Topal


    Magnesium (Mg2+), an essential ion for cells and biological systems, is involved in a variety of cellular processes, including the formation and breakdown of microtubules. The results of a previous investigation suggested that as cells grow the intracellular Mg2+ concentration falls, thereby stimulating formation of the mitotic spindle. In the present work, we used a Mg2+-deficient Schizosaccharomyces pombe strain GA2, in which two essential membrane Mg2+ transporter genes (homologs of ALR1 and ALR2 in Saccharomyces cerevisae) were deleted, and its parental strain Sp292, to examine the extent to which low Mg2+ concentrations can affect mitotic spindle formation. The two S. pombe strains were transformed with a plasmid carrying a GFP-α2-tubulin construct to fluorescently label microtubules. Using the free Mg2+-specific fluorescent probe mag-fura-2, we confirmed that intracellular free Mg2+ levels were lower in GA2 than in the parental strain. Defects in interphase microtubule organization, a lower percentage of mitotic spindle formation and a reduced mitotic index were also observed in the GA2 strain. Although there was interphase microtubule polymerization, the lower level of mitotic spindle formation in the Mg2+-deficient strain suggested a greater requirement for Mg2+ in this phenomenon than previously thought. PMID:27560651

  17. Hydrothermal synthesis of NaEuF4 spindle-like nanocrystals

    Zhi-Jun Wang; Feng Tao; Wei-Li Cai; Lian-Zeng Yao; Xiao-Guang Li


    NaEuF4 spindle-like nanocrystals have been synthesized through a simple hydrothermal method. The nanocrystals were well crystallized and exhibited fine morphology, as indicated by X-ray diffraction, transmission electron microscope and selected area electron diffractometer. The luminescence properties of these NaEuF4 products were investigated.




    The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine durin

  19. Ultrasonographic assessment of the swelling of the human masseter muscle after static and dynamic activity

    Bakke, M; Thomsen, C E; Vilmann, A;


    min at maximum (median endurance time 7.1 min). For dynamic activity, the same individuals chewed gum unilaterally until exhaustion or 40 min at maximum (all endured 40 min) with a cycle time of 725 ms, an average load of 9.3% of maximal electromyographic activity (maxEMG) and a peak mean voltage of...

  20. Population dynamics of active and total ciliate populations in arable soil amended with wheat

    Ekelund, F.; Frederiksen, Helle B.; Ronn, R.


    population may be encysted. The factors governing the dynamics of active and encysted cells in the soil are not well understood. Our objective was to determine the dynamics of active and encysted populations of ciliates during the decomposition of freshly added organic material. We monitored, in soil...... mathematical modeling. Following the addition of fresh organic material, bacterial numbers increased more than 1,400-fold. There was a temporary increase in the number of active ciliates, followed by a rapid decline, although the size of the bacterial prey populations remained high. During this initial burst...

  1. Dynamic Statistical Profiling of Communication Activity in Distributed Applications

    Vetter, J


    A complete trace of communication activity for a terascale application is overwhelming in terms of overhead and storage. We propose a novel alternative that enables profiling of the application's communication activity using statistical message sampling during runtime. We have implemented an operational prototype and our evidence shows that this new technique can provide an accurate, low-overhead, tractable alternative for performance analysis of communication activity. Moreover, this alternative enables an assortment of runtime analysis techniques not previously available with post-mortem, trace-based systems. Our assessment of relative performance and coverage of different sampling and analysis methods shows that purely random selection is preferred over counter- and timer-based sampling. Experiments on several applications running up to 128 processors demonstrate the viability of this approach. In particular, on one application, statistical profiling results contradict conclusions based on evidence from tracing. The design of our prototype reveals that parsimonious modifications to the MPI runtime system could facilitate such techniques on production computing systems, and it suggests that this sampling technique could execute continuously for long-running applications.

  2. Genetic and logic networks with the signal-inhibitor-activator structure are dynamically robust

    LI Fangting; TAN Ning


    The proteins, DNA and RNA interaction networks govern various biological functions in living cells, these networks should be dynamically robust in the intracellular and environmental fluctuations. Here, we use Boolean network to study the robust structure of both genetic and logic networks. First, SOS network in bacteria E. coli, which regulates cell survival and repair after DNA damage, is shown to be dynamically robust. Comparing with cell cycle network in budding yeast and flagella network in E. coli, we find the signal-inhibitor-activator (SIA) structure in transcription regulatory networks. Second, under the dynamical rule that inhibition is much stronger than activation, we have searched 3-node non-self-loop logical networks that are dynamically robust, and that if the attractive basin of a final attractor is as large as seven, and the final attractor has only one active node, then the active node acts as inhibitor, and the SIA and signal-inhibitor (SI) structures are fundamental architectures of robust networks. SIA and SI networks with dynamic robustness against environment uncertainties may be selected and maintained over the course of evolution, rather than blind trial-error testing and be ing an accidental consequence of particular evolutionary history. SIA network can perform a more complex process than SI network, andSIA might be used to design robust artificial genetic network. Our results provide dynamical support for why the inhibitors and SIA/SI structures are frequently employed in cellular regulatory networks.

  3. Role of fungal dynein in hyphal growth, microtubule organization, spindle pole body motility and nuclear migration.

    Inoue, S; Turgeon, B G; Yoder, O C; Aist, J R


    Cytoplasmic dynein is a microtubule-associated motor protein with several putative subcellular functions. Sequencing of the gene (DHC1) for cytoplasmic dynein heavy chain of the filamentous ascomycete, Nectria haematococca, revealed a 4,349-codon open reading frame (interrupted by two introns) with four highly conserved P-loop motifs, typical of cytoplasmic dynein heavy chains. The predicted amino acid sequence is 78.0% identical to the cytoplasmic dynein heavy chain of Neurospora crassa, 70.2% identical to that of Aspergillus nidulans and 24.8% identical to that of Saccharomyces cerevisiae. The genomic copy of DHC1 in N. haematococca wild-type strain T213 was disrupted by inserting a selectable marker into the central motor domain. Mutants grew at 33% of the wild-type rate, forming dense compact colonies composed of spiral and highly branched hyphae. Major cytological phenotypes included (1) absence of aster-like arrays of cytoplasmic microtubules focused at the spindle pole bodies of post-mitotic and interphase nuclei, (2) limited post-mitotic nuclear migration, (3) lack of spindle pole body motility at interphase, (4) failure of spindle pole bodies to anchor interphase nuclei, (5) nonuniform distribution of interphase nuclei and (6) small or ephemeral Spitzenkörper at the apices of hyphal tip cells. Microtubule distribution in the apical region of tip cells of the mutant was essentially normal. The nonuniform distribution of nuclei in hyphae resulted primarily from a lack of both post-mitotic nuclear migration and anchoring of interphase nuclei by the spindle pole bodies. The results support the hypothesis that DHC1 is required for the motility and functions of spindle pole bodies, normal secretory vesicle transport to the hyphal apex and normal hyphal tip cell morphogenesis. PMID:9580563

  4. Encoding four gene expression programs in the activation dynamics of a single transcription factor.

    Hansen, Anders S; O'Shea, Erin K


    Cellular signaling response pathways often exhibit a bow-tie topology [1,2]: multiple upstream stress signals converge on a single shared transcription factor, which is thought to induce different downstream gene expression programs (Figure 1A). However, if several different signals activate the same transcription factor, can each signal then induce a specific gene expression response? A growing body of literature supports a temporal coding theory where information about environmental signals can be encoded, at least partially, in the temporal dynamics of the shared transcription factor [1,2]. For example, in the case of the budding yeast transcription factor Msn2, different stresses induce distinct Msn2 activation dynamics: Msn2 shows pulsatile nuclear activation with dose-dependent frequency under glucose limitation, but sustained nuclear activation with dose-dependent amplitude under oxidative stress [3]. These dynamic patterns can then lead to differential gene expression responses [3-5], but it is not known how much specificity can be obtained. Thus, a major question of this temporal coding theory is how many gene response programs or cellular functions can be robustly encoded by dynamic control of a single transcription factor. Here we provide the first direct evidence that, simply by regulating the activation dynamics of a single transcription factor, it is possible to preferentially induce four distinct gene expression programs. PMID:27046808

  5. Generalized activity equations for spiking neural network dynamics

    Michael A Buice


    Full Text Available Much progress has been made in uncovering the computational capabilities of spiking neural networks. However, spiking neurons will always be more expensive to simulate compared to rate neurons because of the inherent disparity in time scales - the spike duration time is much shorter than the inter-spike time, which is much shorter than any learning time scale. In numerical analysis, this is a classic stiff problem. Spiking neurons are also much more difficult to study analytically. One possible approach to making spiking networks more tractable is to augment mean field activity models with some information about spiking correlations. For example, such a generalized activity model could carry information about spiking rates and correlations between spikes self-consistently. Here, we will show how this can be accomplished by constructing a complete formal probabilistic description of the network and then expanding around a small parameter such as the inverse of the number of neurons in the network. The mean field theory of the system gives a rate-like description. The first order terms in the perturbation expansion keep track of covariances.

  6. Exploring the spectrum of dynamical regimes and timescales in spontaneous cortical activity.

    Mattia, Maurizio; Sanchez-Vives, Maria V


    Rhythms at slow (inhibiting the neurons firing in an activity-dependent manner. Varying pharmacologically the excitability level of brain slices we exploit the network dynamics underlying slow rhythms, uncovering an intrinsic anticorrelation between Up and Down state durations. Besides, a non-monotonic change of Down state duration is also observed, which shrinks the distribution of the accessible frequencies of the slow rhythms. Attractor dynamics with activity-dependent self-inhibition predicts a similar trend even when the system excitability is reduced, because of a stability loss of Up and Down states. Hence, such cortical rhythms tend to display a maximal size of the distribution of Up/Down frequencies, envisaging the location of the system dynamics on a critical boundary of the parameter space. This would be an optimal solution for the system in order to display a wide spectrum of dynamical regimes and timescales. PMID:23730355

  7. PREFACE: Cooperative dynamics Cooperative dynamics

    Gov, Nir


    The dynamics within living cells are dominated by non-equilibrium processes that consume chemical energy (usually in the form of ATP, adenosine triphosphate) and convert it into mechanical forces and motion. The mechanisms that allow this conversion process are mostly driven by the components of the cytoskeleton: (i) directed (polar) polymerization of filaments (either actin or microtubules) and (ii) molecular motors. The forces and motions produced by these two components of the cytoskeleton give rise to the formation of cellular shapes, and drive the intracellular transport and organization. It is clear that these systems present a multi-scale challenge, from the physics of the molecular processes to the organization of many interacting units. Understanding the physical nature of these systems will have a large impact on many fundamental problems in biology and break new grounds in the field of non-equilibrium physics. This field of research has seen a rapid development over the last ten years. Activities in this area range from theoretical and experimental work on the underlying fundamental (bio)physics at the single-molecule level, to investigations (in vivo and in vitro) of the dynamics and patterns of macroscopic pieces of 'living matter'. In this special issue we have gathered contributions that span the whole spectrum of length- and complexity-scales in this field. Some of the works demonstrate how active forces self-organize within the polymerizing cytoskeleton, on the level of cooperative cargo transport via motors or due to active fluxes at the cell membrane. On a larger scale, it is shown that polar filaments coupled to molecular motors give rise to a huge variety of surprising dynamics and patterns: spontaneously looping rings of gliding microtubules, and emergent phases of self-organized filaments and motors in different geometries. All of these articles share the common feature of being out-of-equilibrium, driven by metabolism. As demonstrated here

  8. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.


    Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective: To...... domain that are activated by TF and help to make FVIIa an efficient catalyst of FIX and FX activation....

  9. A dynamic neural field architecture for a pro-active assistant robot

    Pinheiro, Manuel; Bicho, E.; Erlhagen, Wolfram


    We present a control architecture for non-verbal HRI that allows an assistant robot to have a pro-active and anticipatory behavior. The architecture implements the coordination of actions and goals among the human, that needs help, and the robot as a dynamic process that integrates contextual cues, shared task knowledge and predicted outcome of the human motor behavior. The robot control architecture is formalized by a coupled system of dynamic neural fields representing a distributed network...

  10. Phase Locking Phenomena and Electroencephalogram-Like Activities in Dynamic Neuronal Systems

    XU Xin-Jian; WANG Sheng-Jun; TANG Wei; WANG Ying-Hai


    @@ We study signal detection and transduction of dynamic neuronal systems under the influence of external noise,white and coloured. Based on simulations, we show explicitly phase locking phenomena between the output and the input of a single neuron and Electroencephalogram-like activities on neural networks with small-world connectivity. The numerical results prove that the dynamic neuronal system can be adjusted to an optimal sensitive state for signal processing in the presence of additive noise.

  11. Active Control Of Oscillation Patterns In Nonlinear Dynamical Systems And Their Mathematical Modelling

    Šutová Zuzana; Vrábeľ Róbert


    The article deals with the active control of oscillation patterns in nonlinear dynamical systems and its possible use. The purpose of the research is to prove the possibility of oscillations frequency control based on a change of value of singular perturbation parameter placed into a mathematical model of a nonlinear dynamical system at the highest derivative. This parameter is in singular perturbation theory often called small parameter, as ε → 0+. Oscillation frequency change caused by a di...

  12. Dynamics of lipid metabolism under the physical activity influence

    Evdokimov E.I.


    Full Text Available The results of influence of the physical loading are considered on the state of lipid exchange for practically healthy people and patients with a general metabolic syndrome. In research 38 sportsmen in age 22 - 27 years and 20 patients (women and men took part by age of 35-47лет. Influence of physical exercises was estimated on the indexes of biochemical composition of blood, anthropometry, arteriotony. The complex of physical exercises was used in common with a dietotherapy during 4 months. It is set that a complex causes regression of pathological displays. Physical activity has an unidirectional effect on lipid metabolism both in athletes and persons suffering from metabolic disorders.

  13. Dynamic model for selective metabolic activation in chemical carcinogenesis

    Selkirk, J.K.; MacLeod, M.C.


    Theoretical calculations predict the relative ease of formation of carbonium ions from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene-9,10-oxide or from either of the 2 symmetrical bay regions of B(e)P, and suggest their attraction to cellular nucleophiles. When both isomers were metabolized by hamster embryo fibroblasts (HEF) and the products analyzed, the results showed that the probable reason for benzo(e)pyrene's lack of carcinogenicity was its metabolic preference to attack the molecule away from the bay-region area. Particularly striking was the absence of any evidence for the formation of a significant amount of B(e)P-9,10-dihydrodiol. This suggests a metabolic basis for the relative lack of carcinogenic and mutagenic activity of B(e)P. The reason for this is not clear but may be due to physical or chemical factors such as membrane solubility or stereochemical requirements of the active site of the enzyme. The bay-region theory of PAH carcinogenesis predicts that carbonium ion formation from 9,10-dihydro-9,10-dihydroxybenzo(e)pyrene-11, 12-oxide, if formed, would be energetically favorable. Thus, the inability of HEF and microcomes to form B(e)P-9,10-dihydrodiol, the precursor of its potentially highly reactive diol-epoxide, would explain the relative inertness of B(e)P in several biological systems. As the subtle biochemical interactions of the various carcinogen intermediates become clarified, it becomes apparent that susceptibility and resistance to malignant transformation are based on a complex set of both chemical and physical parameters. It is becoming clear that metabolism kinetics, membrane interaction, and the role of nuclear metabolism help dictate the passage of the carcinogen and its reactive intermediates into and through the metabolic machinery of the cell. (ERB)

  14. Effects of Dynamic and Static Stretching Within General and Activity Specific Warm-Up Protocols

    Michael Samson; Button, Duane C.; Anis Chaouachi; Behm, David G.


    The purpose of the study was to determine the effects of static and dynamic stretching protocols within general and activity specific warm-ups. Nine male and ten female subjects were tested under four warm-up conditions including a 1) general aerobic warm-up with static stretching, 2) general aerobic warm-up with dynamic stretching, 3) general and specific warm-up with static stretching and 4) general and specific warm-up with dynamic stretching. Following all conditions, subjects were tested...

  15. Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics

    Roy, S.


    Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff, (M1) and Hivep1, Nfil3, Prdm1, (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.

  16. Energy transfer modelling of active thermoacoustic engines via Lagrangian thermoacoustic dynamics

    Highlights: • Resonant control on thermoacoustic engines to amplify power rating. • Least-action principle of thermoacoustic dynamics to shape engine chamber. • Spatiotemporal transfer function into feedback systems. • Conservation law of thermoacoustic storage to figure out engine cycles. • Robin boundary condition to identify flow leakage. - Abstract: This paper develops energy-transfer modelling of active thermoacoustic engines resonantly controlled on boundary for amplification of power rating toward satisfaction of renewable industry. Therein the wave equation of thermoacoustic dynamics in resonators with non-uniform media and boundary actuations is derived and then turned into a least-action principle. With this least-action principle, we obtain the governing equation of longitudinal resonators with spatially variant cross-section areas to investigate how to shape the resonator for boosting piston stroke and power-transmission efficiency. It is followed by spatiotemporal transfer-function modelling that functionally represents the dynamics and interprets the boundary actuations into internal inputs. This helps formulate the overall dynamics into feedback-interconnection between the thermoacoustic dynamics in the resonator and the mechatronic dynamics of the alternative current generator, so that synthesis of feedback systems can be applied to design the entire engine. Transfer-function modelling following least-action principle leads to the conservation law of thermoacoustic storage, which figures out engine cycles, the most fundamental principle in designing active thermoacoustic engines. Based on such feedback realization, digital signal processing is programmed to numerically assess power ratings of active designs

  17. Dynamics of firing patterns, synchronization and resonances in neuronal electrical activities: experiments and analysis

    Qishao Lu; Huaguang Gu; Zhuoqin Yang; Xia Shi; Lixia Duan; Yanhong Zheng


    Recent advances in the experimental and theore-tical study of dynamics of neuronal electrical firing activi-ties are reviewed. Firstly, some experimental phenomena of neuronal irregular firing patterns, especially chaotic and sto-chastic firing patterns, are presented, and practical nonlinear time analysis methods are introduced to distinguish deter-ministic and stochastic mechanism in time series. Secondly, the dynamics of electrical firing activities in a single neu-ron is concerned, namely, fast-slow dynamics analysis for classification and mechanism of various bursting patterns, one- or two-parameter bifurcation analysis for transitions of firing patterns, and stochastic dynamics of firing activities (stochastic and coherence resonances, integer multiple and other firing patterns induced by noise, etc.). Thirdly, different types of synchronization of coupled neurons with electri-cal and chemical synapses are discussed. As noise and time delay are inevitable in nervous systems, it is found that noise and time delay may induce or enhance synchronization and change firing patterns of coupled neurons. Noise-induced resonance and spatiotemporal patterns in coupled neuronal networks are also demonstrated. Finally, some prospects are presented for future research. In consequence, the idea and methods of nonlinear dynamics are of great significance in exploration of dynamic processes and physiological func-tions of nervous systems.

  18. Toward high-dynamic active mirrors for LGS refocusing systems

    Hugot, Emmanuel; Madec, Fabrice; Vives, Sébastien; Ferrari, Marc; Le Mignant, David; Cuby, Jean Gabriel


    In the frame of the E-ELT-EAGLE instrument phase A studies, we designed a convex VCM able to compensate for the focus variation on the Laser Guide Star (LGS) wavefront sensor, due to the elevation of the telescope and the fixed sodium layer altitude. We present an original optical design including this active convex mirror, providing a large sag variation on a spherical surface with a 120mm clear aperture, with an optical quality better than lambda/5 RMS up to 820μm of sag and better than lambda/4 RMS up to 1000μm of sag. Finite element analysis (FEA) allowed an optimisation of the mirror's variable thickness distribution to compensate for geometrical and material non linearity. Preliminary study of the pre-stressing has also been performed by FEA, showing that a permanent deformation remains after removal of the loads. Results and comparison with the FEA are presented in the article of F.Madec et al (AS10-7736-119, this conference), with an emphasis on the system approach.

  19. Time-Varying Total Stiffness Matrix of a Rigid Machine Spindle-Angular Contact Ball Bearings Assembly: Theory and Analytical/Experimental Verifications

    Fawzi M.A. El-Saeidy


    Full Text Available A lagrangian formulation is presented for the total dynamic stiffness and damping matrices of a rigid rotor carrying noncentral rigid disk and supported on angular contact ball bearings (ACBBs. The bearing dynamic stiffness/damping marix is derived in terms of the bearing motions (displacements/rotations and then the principal of virtual work is used to transfer it from the bearing location to the rotor mass center to obtain the total dynamic stiffness/damping matrix. The bearing analyses take into account the bearing nonlinearities, cage rotation and bearing axial preload. The coefficients of these time-dependent matrices are presented analytically. The equations of motion of a rigid rotor-ACBBs assembly are derived using Lagrange's equation. The proposed analyses on deriving the bearing stiffness matrix are verified against existing bearing analyses of SKF researchers that, in turn, were verified using both SKF softwares/experiments and we obtained typical agreements. The presented total stiffness matrix is applied to a typical grinding machine spindle studied experimentally by other researchers and excellent agreements are obtained between our analytical eigenvalues and the experimental ones. The effect of using the total full stiffness matrix versus using the total diagonal stiffness matrix on the natural frequencies and dynamic response of the rigid rotor-bearings system is studied. It is found that using the diagonal matrix affects natural frequencies values (except the axial frequency and response amplitudes and pattern and causes important vibration tones to be missig from the response spectrum. Therefore it is recommended to use the full total stiffness matrix and not the diagonal matrix in the design/vibration analysis of these rotating machines. For a machine spindle-ACBBs assembly under mass unbalnce and a horizontal force at the spindle cutting nose when the bearing time-varying stiffness matrix (bearing cage rotation is considered

  20. Estimation of muscle activity using higher-order derivatives, static optimization, and forward-inverse dynamics.

    Yamasaki, Taiga; Idehara, Katsutoshi; Xin, Xin


    We propose a new method to estimate muscle activity in a straightforward manner with high accuracy and relatively small computational costs by using the external input of the joint angle and its first to fourth derivatives with respect to time. The method solves the inverse dynamics problem of the skeletal system, the forward dynamics problem of the muscular system, and the load-sharing problem of muscles as a static optimization of neural excitation signals. The external input including the higher-order derivatives is required for a calculation of constraints imposed on the load-sharing problem. The feasibility of the method is demonstrated by the simulation of a simple musculoskeletal model with a single joint. Moreover, the influences of the muscular dynamics, and the higher-order derivatives on the estimation of the muscle activity are demonstrated, showing the results when the time constants of the activation dynamics are very small, and the third and fourth derivatives of the external input are ignored, respectively. It is concluded that the method can have the potential to improve estimation accuracy of muscle activity of highly dynamic motions. PMID:27211782

  1. The emergence of sarcomeric, graded-polarity and spindle-like patterns in bundles of short cytoskeletal polymers and two opposite molecular motors

    We use linear stability analysis and numerical solutions of partial differential equations to investigate pattern formation in the one-dimensional system of short dynamic polymers and one (plus-end directed) or two (one is plus-end, another minus-end directed) molecular motors. If polymer sliding and motor gliding rates are slow and/or the polymer turnover rate is fast, then the polymer-motor bundle has mixed polarity and homogeneous motor distribution. However, if motor gliding is fast, a sarcomeric pattern with periodic bands of alternating polymer polarity separated by motor aggregates evolves. On the other hand, if polymer sliding is fast, a graded-polarity bundle with motors at the center emerges. In the presence of the second, minus-end directed motor, the sarcomeric pattern is more ubiquitous, while the graded-polarity pattern is destabilized. However, if the minus-end motor is weaker than the plus-end directed one, and/or polymer nucleation is autocatalytic, and/or long polymers are present in the bundle, then a spindle-like architecture with a sorted-out polarity emerges with the plus-end motors at the center and minus-end motors at the edges. We discuss modeling implications for actin-myosin fibers and in vitro and meiotic spindles.

  2. Active site dynamics of toluene hydroxylation by cytochrome P-450

    Rat liver cytochrome P-450 hydroxylates toluene to benzyl alcohol plus o-, m-, and p-cresol. Deuterated toluenes were incubated under saturating conditions with liver microsomes from phenobarbital-pretreated rats, and product yields and ratios were measured. Stepwise deuteration of the methyl leads to stepwise decreases in the alcohol/cresol ratio without changing the cresol isomer ratios. Extensive deuterium retention in the benzyl alcohols from PhCH2D and PhCHD2 suggests there is a large intrinsic isotope effect for benzylic hydroxylation. After replacement of the third benzylic H by D, the drop in the alcohol/cresol ratio was particularly acute, suggsting that metabolic switching from D to H within the methyl group was easier than switching from the methyl to the ring. Comparison of the alcohol/cresol ratio for PhCH3 vs PhCD3 indicated a net isotope effect of 6.9 for benzylic hydroxylation. From product yield data for PhCH3 and PhCD3, DV for benzyl alcohol formation is only 1.92, whereas DV for total product formation is 0.67 (i.e., inverse). From competitive incubations of PhCH3/PhCD3 mixtures D(V/K) isotope effects on benzyl alcohol formation and total product formation (3.6 and 1.23, respectively) are greatly reduced, implying strong commitment to catalysis. In contrast, D(V/K) for the alcohol/cresol ratio is 6.3, indicating that the majority of the intrinsic isotope effect is expressed through metabolic switching. Overall, these data are consistent with reversible formation of a complex between toluene and the active oxygen form of cytochrome P-450, which rearranges internally and reacts to form products faster than it dissociates back to release substrate

  3. Wave-Activity Conservation Laws and Stability Theorems for Semi-Geostrophic Dynamics.

    Kushner, Paul Joel

    Our understanding of the role that large-scale eddies play in the atmospheric general circulation is largely based on theoretical results developed using quasi-geostrophic (QG) dynamics. This dissertation represents part of an overall effort to extend these important results to more accurate dynamical models than the seriously limited QG model. In this dissertation, a body of QG theory, concerning the evolution of disturbances to prescribed basic states, is systematically generalized to the semi-geostrophic (SG) model. This body of theory consists of wave-activity conservation laws, linear and nonlinear stability theorems for parallel and non-parallel basic states, and wave-zonal-mean-flow interaction theory. The generalization exploits the two key features of Hamiltonian structure and balanced dynamics that SG and QG dynamics share. The abovementioned theory arises from the conservation of finite-amplitude pseudomomentum and pseudoenergy wave -activity invariants. In an introductory review, these invariants are derived for QG dynamics and shown to yield the body of QG theory, including an apparently novel finite -amplitude generalization of the QG wave-zonal-mean-flow interaction theory. The same procedure is then carried out first for f-plane Boussinesq and then for beta-plane compressible SG dynamics. The body of SG theory is analogous to the QG one and reduces to it in the small-Rossby-number limit. Two important differences between SG and QG dynamics complicate the generalization but yield novel insights and results. First, the transformation to isentropic and geostrophic coordinates in the SG model simplifies the dynamics to a 'potential-vorticity-invertible' form free of explicit ageostrophic advection terms but introduces complex boundary variability in the transformed space. Boundary contributions are here incorporated explicitly into the wave-activity and stability results, yielding novel lateral -boundary stabilty criteria. Second, the SG invertibility

  4. Acrylamide effects on kinesin-related proteins of the mitotic/meiotic spindle

    The microtubule (MT) motor protein kinesin is a vital component of cells and organs expressing acrylamide (ACR) toxicity. As a mechanism of its potential carcinogenicity, we determined whether kinesins involved in cell division are inhibited by ACR similar to neuronal kinesin [Sickles, D.W., Brady, S.T., Testino, A.R., Friedman, M.A., and Wrenn, R.A. (1996). Direct effect of the neurotoxicant acrylamide on kinesin-based microtubule motility. Journal of Neuroscience Research 46, 7-17.] Kinesin-related genes were isolated from rat testes [Navolanic, P.M., and Sperry, A.O. (2000). Identification of isoforms of a mitotic motor in mammalian spermatogenesis. Biology of Reproduction 62, 1360-1369.], their kinesin-like proteins expressed in bacteria using recombinant DNA techniques and the effects of ACR, glycidamide (GLY) and propionamide (a non-neurotoxic metabolite) on the function of two of the identified kinesin motors were tested. KIFC5A MT bundling activity, required for mitotic spindle formation, was measured in an MT-binding assay. Both ACR and GLY caused a similar concentration-dependent reduction in the binding of MT; concentrations of 100 μM ACR or GLY reduced its activity by 60%. KRP2 MT disassembling activity was assayed using the quantity of tubulin disassembled from taxol-stabilized MT. Both ACR and GLY inhibited KRP2-induced MT disassembly. GLY was substantially more potent; significant reductions of 60% were achieved by 500 μM, a comparable inhibition by ACR required a 5 mM concentration. Propionamide had no significant effect on either kinesin, except KRP2 at 10 mM. This is the first report of ACR inhibition of a mitotic/meiotic motor protein. ACR (or GLY) inhibition of kinesin may be an alternative mechanism to DNA adduction in the production of cell division defects and potential carcinogenicity. We conclude that ACR may act on multiple kinesin family members and produce toxicities in organs highly dependent on microtubule-based functions

  5. Re-presentation of Olfactory Exposure Therapy Success Cues during Non-Rapid Eye Movement Sleep did not Increase Therapy Outcome but Increased Sleep Spindles

    Rihm, Julia S.; Sollberger, Silja B.; Soravia, Leila M.; Rasch, Björn


    Exposure therapy induces extinction learning and is an effective treatment for specific phobias. Sleep after learning promotes extinction memory and benefits therapy success. As sleep-dependent memory-enhancing effects are based on memory reactivations during sleep, here we aimed at applying the beneficial effect of sleep on therapy success by cueing memories of subjective therapy success during non-rapid eye movement sleep after in vivo exposure-based group therapy for spider phobia. In addition, oscillatory correlates of re-presentation during sleep (i.e., sleep spindles and slow oscillations) were investigated. After exposure therapy, spider-phobic patients verbalized their subjectively experienced therapy success under presence of a contextual odor. Then, patients napped for 90 min recorded by polysomnography. Half of the sleep group received the odor during sleep while the other half was presented an odorless vehicle as control. A third group served as a wake control group without odor presentation. While exposure therapy significantly reduced spider-phobic symptoms in all subjects, these symptoms could not be further reduced by re-presenting the odor associated with therapy success, probably due to a ceiling effect of the highly effective exposure therapy. However, odor re-exposure during sleep increased left-lateralized frontal slow spindle (11.0–13.0 Hz) and right-lateralized parietal fast spindle (13.0–15.0 Hz) activity, suggesting the possibility of a successful re-presentation of therapy-related memories during sleep. Future studies need to further examine the possibility to enhance therapy success by targeted memory reactivation (TMR) during sleep. PMID:27445775


    Michael Samson


    Full Text Available The purpose of the study was to determine the effects of static and dynamic stretching protocols within general and activity specific warm-ups. Nine male and ten female subjects were tested under four warm-up conditions including a 1 general aerobic warm-up with static stretching, 2 general aerobic warm-up with dynamic stretching, 3 general and specific warm-up with static stretching and 4 general and specific warm-up with dynamic stretching. Following all conditions, subjects were tested for movement time (kicking movement of leg over 0.5 m distance, countermovement jump height, sit and reach flexibility and 6 repetitions of 20 metre sprints. Results indicated that when a sport specific warm-up was included, there was an 0.94% improvement (p = 0.0013 in 20 meter sprint time with both the dynamic and static stretch groups. No such difference in sprint performance between dynamic and static stretch groups existed in the absence of the sport specific warm-up. The static stretch condition increased sit and reach range of motion (ROM by 2.8% more (p = 0.0083 than the dynamic condition. These results would support the use of static stretching within an activity specific warm-up to ensure maximal ROM along with an enhancement in sprint performance

  7. Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process

    Miao, Yinglong [ORNL; Baudry, Jerome Y [ORNL


    Long-timescale molecular dynamics simulations (300 ns) are performed on both the apo- (i.e., camphor-free) and camphor-bound cytochrome P450cam (CYP101). Water diffusion into and out of the protein active site is observed without biased sampling methods. During the course of the molecular dynamics simulation, an average of 6.4 water molecules is observed in the camphor-binding site of the apo form, compared to zero water molecules in the binding site of the substrate-bound form, in agreement with the number of water molecules observed in crystal structures of the same species. However, as many as 12 water molecules can be present at a given time in the camphor-binding region of the active site in the case of apo-P450cam, revealing a highly dynamic process for hydration of the protein active site, with water molecules exchanging rapidly with the bulk solvent. Water molecules are also found to exchange locations frequently inside the active site, preferentially clustering in regions surrounding the water molecules observed in the crystal structure. Potential-of-mean-force calculations identify thermodynamically favored trans-protein pathways for the diffusion of water molecules between the protein active site and the bulk solvent. Binding of camphor in the active site modifies the free-energy landscape of P450cam channels toward favoring the diffusion of water molecules out of the protein active site.

  8. Age-related shifts in brain activity dynamics during task switching.

    Jimura, Koji; Braver, Todd S


    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and sustained neural activity associated with cognitive control. Relative to young adults, older adults exhibited not only decreased sustained activity in the anterior prefrontal cortex (aPFC) during task-switching blocks but also increased transient activity on task-switch trials. Another pattern of age-related shift in dynamics was present in the lateral PFC (lPFC) and posterior parietal cortex (PPC), with younger adults showing a cue-related response during task-switch trials in lPFC and PPC, whereas older adults exhibited switch-related activation during the cue period in PPC only. In all 3 regions, these qualitatively distinct patterns of brain activity predicted qualitatively distinct patterns of behavioral performance across the 2 age groups. Together, these results suggest that older adults may shift from a proactive to reactive cognitive control strategy as a means of retaining relatively preserved behavioral performance in the face of age-related neurocognitive changes. PMID:19805420

  9. The Theory of Dynamics of Living Systems Activity in Interpersonal Interaction

    Sergei V. Kharitonov


    Full Text Available The work deals with the study of the dynamics of the interaction between people. The theoretical basis of the research is the model of the dynamics of living systems activity, stating the existence of three phases of systems dynamics: termnet, affinity and involvement. The equivalents of these phrases in interpersonal communication are the following: prudence during interaction (equivalent to termnet phase, readiness to avow one’s goals (equivalent to affinity phase, readiness to plan united actions (equivalent to involvement phase. The goal of the research is to study the process of interaction between two persons from the perspective of the theory of dynamics of living systems activity. The participants were offered to enter into agreement during an hour. The time limit of their dialogue had three 20-minute periods. The level of prudence, readiness to discuss goals and plan united actions were estimated every three time segments, using visual-analogue scale. The research was conducted in the group, involving 42 people. The obtained results showed that the communication structure, projected by the theory of dynamics activity seems to be convincing and can be used to describe communicative interactions.

  10. Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands

    Vettoretti, Gerolamo; Moroni, Elisabetta; Sattin, Sara; Tao, Jiahui; Agard, David A.; Bernardi, Anna; Colombo, Giorgio


    Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone’s active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators.

  11. Emergent Structures in an Active Polar Fluid : dynamics of shape, scattering and merger

    Husain, Kabir


    Spatially localised defect structures emerge spontaneously in a hydrodynamic description of an active polar fluid comprising polar 'actin' filaments and 'myosin' motor proteins that (un)bind to filaments and exert active contractile stresses. These emergent defect structures are characterized by distinct textures and can be either static or mobile - we derive effective equations of motion for these 'extended particles' and analyse their shape, kinetics, interactions and scattering. Depending on the impact parameter and propulsion speed, these active defects undergo elastic scattering or merger. Our results are relevant for the dynamics of actomyosin-dense structures at the cell cortex, reconstituted actomyosin complexes and 2D active colloidal gels.

  12. Interplay of cytoskeletal activity and lipid phase stability in dynamic protein recruitment and clustering.

    Gómez-Llobregat, Jordi; Buceta, Javier; Reigada, Ramon


    Recent experiments have revealed that some membrane proteins aggregate to form clusters. This type of process has been proven to be dynamic and to be actively maintained by external kinetics. Additionally, this dynamic recruiting is cholesterol- and actin-dependent, suggesting that raft organization and cytoskeleton rearrangement play a crucial role. In the present study, we propose a simple model that provides a general framework to describe the dynamical behavior of lipid-protein assemblies. Our results suggest that lipid-mediated interactions and cytoskeleton-anchored proteins contribute to the modulation of such behavior. In particular, we find a resonant condition between the membrane protein and cytoskeleton dynamics that results in the invariance of the ratio of clustered proteins that is found in in vivo experimental observations. PMID:24018870

  13. Model of myosin recruitment to the cell equator for cytokinesis: feedback mechanisms and dynamical regimes

    Veksler, Alexander; Vavylonis, Dimitrios


    The formation and constriction of the contractile ring during cytokinesis, the final step of cell division, depends on the recruitment of motor protein myosin to the cell's equatorial region. During animal cell cytokinesis, cortical myosin filaments (MF) disassemble at the flanking regions and concentrate in the equator. This recruitment depends on myosin motor activity and the Rho proteins that regulate MF assembly and disassembly. Central spindle and astral microtubules help establish a spatial pattern of differential Rho activity. We propose a reaction-diffusion model for the dynamics of MF recruitment to the equatorial region. In the model, the central spindle and mechanical stress promote self-reinforcing MF assembly. Negative feedback is introduced by MF-induced recruitment of inhibitor myosin phosphatase. Our model yields various dynamical regimes and explains both the recruitment of MF to the cleavage furrow and the observed damped MF oscillations in the flanking regions, as well as steady MF assembly. Space and time parameters of MF oscillations are calculated. We predict oscillatory relaxation of cortical MF upon removal of locally-applied external stress.

  14. Dynamic Loading of Deformable Porous Media Can Induce Active Solute Transport

    Albro, Michael B.; Chahine, Nadeen O; Li, Roland; Yeager, Keith; Hung, Clark T.; Ateshian, Gerard A.


    Active solute transport mediated by molecular motors across porous membranes is a well-recognized mechanism for transport across the cell membrane. In contrast, active transport mediated by mechanical loading of porous media is a non-intuitive mechanism that has only been predicted recently from theory, but not yet observed experimentally. This study uses agarose hydrogel and dextran molecules as a model experimental system to explore this mechanism. Results show that dynamic loading can enha...

  15. Temporal dynamics of musical emotions examined through intersubject synchrony of brain activity.

    Trost, W.; Frühholz, S.; Cochrane, T.; Cojan, Y.; Vuilleumier, P.


    To study emotional reactions to music, it is important to consider the temporal dynamics of both affective responses and underlying brain activity. Here, we investigated emotions induced by music using functional magnetic resonance imaging (fMRI) with a data-driven approach based on intersubject correlations (ISC). This method allowed us to identify moments in the music that produced similar brain activity (i.e. synchrony) among listeners under relatively natural listening conditions. Continu...

  16. Dynamic transcription factor activity profiles reveal key regulatory interactions during megakaryocytic and erythroid differentiation.

    Duncan, Mark T; Shin, Seungjin; Wu, Jia J; Mays, Zachary; Weng, Stanley; Bagheri, Neda; Miller, William M; Shea, Lonnie D


    The directed differentiation toward erythroid (E) or megakaryocytic (MK) lineages by the MK-E progenitor (MEP) could enhance the ex vivo generation of red blood cells and platelets for therapeutic transfusions. The lineage choice at the MEP bifurcation is controlled in large part by activity within the intracellular signal transduction network, the output of which determines the activity of transcription factors (TFs) and ultimately gene expression. Although many TFs have been implicated, E or MK differentiation is a complex process requiring multiple days, and the dynamics of TF activities during commitment and terminal maturation are relatively unexplored. Herein, we applied a living cell array for the large-scale, dynamic quantification of TF activities during MEP bifurcation. A panel of hematopoietic TFs (GATA-1, GATA-2, SCL/TAL1, FLI-1, NF-E2, PU.1, c-Myb) was characterized during E and MK differentiation of bipotent K562 cells. Dynamic TF activity profiles associated with differentiation towards each lineage were identified, and validated with previous reports. From these activity profiles, we show that GATA-1 is an important hub during early hemin- and PMA-induced differentiation, and reveal several characteristic TF interactions for E and MK differentiation that confirm regulatory mechanisms documented in the literature. Additionally, we highlight several novel TF interactions at various stages of E and MK differentiation. Furthermore, we investigated the mechanism by which nicotinamide (NIC) promoted terminal MK maturation using an MK-committed cell line, CHRF-288-11 (CHRF). Concomitant with its enhancement of ploidy, NIC strongly enhanced the activity of three TFs with known involvement in terminal MK maturation: FLI-1, NF-E2, and p53. Dynamic profiling of TF activity represents a novel tool to complement traditional assays focused on mRNA and protein expression levels to understand progenitor cell differentiation. PMID:24853077

  17. The Dynamics of fluid flow and associated chemical fluxes at active continental margins

    Solomon, Evan Alan


    Active fluid flow plays an important role in the geochemical, thermal, and physical evolution of the Earth’s crust. This dissertation investigates the active fluid flow and associated chemical fluxes at two dynamic continental margins: The Costa Rica subduction zone and the northern Gulf of Mexico hydrocarbon province, using novel seafloor instrumentation for continuous monitoring of fluid flow rates and chemistry. Traditional pore fluid sampling methods and flow rate models only provide a ...

  18. Molecular dynamics explorations of active site structure in designed and evolved enzymes

    Osuna Oliveras, Sílvia; Jiménez-Osés, Gonzalo; Noey, Elizabeth L.; Houk, Kendall N.


    This Account describes the use of molecular dynamics (MD) simulations to reveal how mutations alter the structure and organization of enzyme active sites. As proposed by Pauling about 70 years ago and elaborated by many others since then, biocatalysis is efficient when functional groups in the active site of an enzyme are in optimal positions for transition state stabilization. Changes in mechanism and covalent interactions are often critical parts of enzyme catalysis. We describe our explora...

  19. Dynamic Changes, Cut-Off Points, Sensitivity, and Specificity of Laboratory Data to Differentiate Macrophage Activation Syndrome from Active Disease

    Raheleh Assari


    Full Text Available Purpose. To compare the laboratory data and changes in these data between patients with MAS and patients with flare-up of the autoimmune diseases. Methods. In a prospective study, the static laboratory data and dynamic changes in the selected data in 17 consecutive patients with MAS and 53 patients with active disease of SJIA, PJIA, Kawasaki disease, and SLE were compared. The ROC curve analysis was used to evaluate cut-off points, sensitivity, and specificity of the static and dynamic laboratory data to differentiate between MAS and active disease. Results. In the MAS group, the mean CRP3, ALT, AST, total bilirubin, ferritin, LDH, PT, PTT, and INR were significantly higher and the mean WBC2, PMN2, Lymph2, Hgb1, 2, 3, ESR2, serum albumin, and sodium were significantly lower than in control group. Some of the important cut-off points were PLT2 38.5, ALT > 38, WBC 5277 ng/mL. Conclusion. The dynamic changes in some laboratory data, especially PLT, can differentiate between MAS and active disease. The changes in WBC, PMN, and ESR and the levels of the liver enzymes may also be helpful in the early differentiation. Very high levels of ferritin may also help the diagnosis along with other clinical and laboratory signs.

  20. Spindle Cell Carcinoma of the Larynx: A Confusing Diagnosis for the Pathologist and Clinician

    Bostanci, Asli; Ozbilim, Gulay; Turhan, Murat


    Laryngeal spindle cell carcinoma (SpCC) is an uncommon subtype of squamous cell carcinoma which represents 0.5% of all laryngeal squamous cell carcinomas. It is a biphasic tumor consisting of the combination of a malignant mesenchymal spindle cell component and a squamous cell component that includes dysplasia, carcinoma in situ, or invasive carcinoma. Although it has aggressive biological features, the probability of making a diagnosis in the early stages is high as it often leads to obstructive symptoms in the early period. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a 60-year-old laryngeal SpCC case that was effectively treated with wide local excision followed by adjuvant radiotherapy was presented with the literature. PMID:26788392


    Ajish M. Saji


    Full Text Available Spindle cell Carcinoma is a rare biphasic neoplasm consisting of epithelial andmesenchymal components and accounts for less than 1% of all tumours of oralregion. It is a rare aggressive variant of squamous cell carcinoma which frequentlyrecurs and metastasizes with poor prognosis compared to classical squamous cellcarcinoma. The biologic behaviour is comparable to poorly differentiated SquamousCell Carcinoma. The 5 year disease free survival rate is approximately 30% for all OralTumors. The variants of squamous cell carcinoma frequently arise in mucosa of upperaerodigestive tract. The most common site in head and neck region is in larynx andhypopharynx; the oral cavity being rarely affected. This biphasic malignant neoplasmoften assumes a sarcomatous appearance and may present diagnostic difficulty. Hencecareful histopathologic analysis is warranted. We report a rare case of spindle cellcarcinoma in unusual location with immunohistochemical findings and review of theliterature.

  2. Surgical and medical management of a uterine spindle cell tumor in an African hedgehog (Atelerix albiventris).

    Done, Lisa B; Deem, Sharon L; Fiorello, Christine V


    A 5-yr-old female African hedgehog (Ateleris albiventris) presented with hematuria. Vulvar culture results revealed a 4+ growth of Enterococcus sp. and gamma-Streptococcus sp. susceptible to trimethoprim sulfa and enrofloxacin. Ultrasound evaluation of the abdomen revealed an unidentifiable tubular structure in the region of the reproductive tract. An exploratory laparotomy and ovariohysterectomy were performed. Pathologic studies of the uterus showed a uterine spindle cell tumor, uterine endometrial polyp, uterine adenomyosis, and a possible acute infarct resulting in uterine wall necrosis. Hematuria did not reoccur, and the hedgehog lived for another 19 mo until she died from an oral squamous cell carcinoma. To date, this is the first report of a uterine spindle cell tumor in an African hedgehog. PMID:18229871

  3. Meiosis I in Xenopus oocytes is not error-prone despite lacking spindle assembly checkpoint.

    Liu, Dandan; Shao, Hua; Wang, Hongmei; Liu, X Johné


    The spindle assembly checkpoint, SAC, is a surveillance mechanism to control the onset of anaphase during cell division. SAC prevents anaphase initiation until all chromosome pairs have achieved bipolar attachment and aligned at the metaphase plate of the spindle. In doing so, SAC is thought to be the key mechanism to prevent chromosome nondisjunction in mitosis and meiosis. We have recently demonstrated that Xenopus oocyte meiosis lacks SAC control. This prompted the question of whether Xenopus oocyte meiosis is particularly error-prone. In this study, we have karyotyped a total of 313 Xenopus eggs following in vitro oocyte maturation. We found no hyperploid egg, out of 204 metaphase II eggs with countable chromosome spreads. Therefore, chromosome nondisjunction is very rare during Xenopus oocyte meiosis I, despite the lack of SAC. PMID:24646611

  4. Spindle Cell Carcinoma of the Larynx: A Confusing Diagnosis for the Pathologist and Clinician

    Asli Bostanci


    Full Text Available Laryngeal spindle cell carcinoma (SpCC is an uncommon subtype of squamous cell carcinoma which represents 0.5% of all laryngeal squamous cell carcinomas. It is a biphasic tumor consisting of the combination of a malignant mesenchymal spindle cell component and a squamous cell component that includes dysplasia, carcinoma in situ, or invasive carcinoma. Although it has aggressive biological features, the probability of making a diagnosis in the early stages is high as it often leads to obstructive symptoms in the early period. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a 60-year-old laryngeal SpCC case that was effectively treated with wide local excision followed by adjuvant radiotherapy was presented with the literature.

  5. In situ growing directional spindle TiO2 nanocrystals on cellulose fibers for enhanced Pb(2+) adsorption from water.

    Li, Yanxiang; Cao, Lixia; Li, Lei; Yang, Chuanfang


    TiO2/cellulose nanocomposite was synthesized by in situ generation of titanium dioxide (TiO2) nanocrystals on cellulose fibers (CF) via facile hydrolysis of TiOSO4. Cellulose was intended as a scaffold to immobilize TiO2 nanoparticles (NPs), but turned out surprisingly to be also a chemical template that directed the crystal growth. As a result, spindle rutile TiO2 crystals were nicely formed on the surface of cellulose. These crystals were further controlled to disperse uniformly without agglomeration for better use of their surface area to adsorb heavy metals. The TiO2/CF composite showed enhanced adsorption capacity, good regenerability and selectivity for lead (Pb(2+)) removal. In addition, the composite fibers were readily fabricated into a nonwoven filter bed through which dynamic filtration experiment was conducted. A 12-fold increase in filtered bed volume was achieved for TiO2/CF bed compared with pure CF bed before breakthrough took place. This work provides a green pathway for fabricating low cost, high efficiency and engineering application possible nanosorbents for water decontamination. PMID:25723888

  6. Decipher the dynamic coordination between enzymatic activity and structural modulation at focal adhesions in living cells

    Lu, Shaoying; Seong, Jihye; Wang, Yi; Chang, Shiou-Chi; Eichorst, John Paul; Ouyang, Mingxing; Li, Julie Y.-S.; Chien, Shu; Wang, Yingxiao


    Focal adhesions (FAs) are dynamic subcellular structures crucial for cell adhesion, migration and differentiation. It remains an enigma how enzymatic activities in these local complexes regulate their structural remodeling in live cells. Utilizing biosensors based on fluorescence resonance energy transfer (FRET), we developed a correlative FRET imaging microscopy (CFIM) approach to quantitatively analyze the subcellular coordination between the enzymatic Src activation and the structural FA disassembly. CFIM reveals that the Src kinase activity only within the microdomain of lipid rafts at the plasma membrane is coupled with FA dynamics. FA disassembly at cell periphery was linearly dependent on this raft-localized Src activity, although cells displayed heterogeneous levels of response to stimulation. Within lipid rafts, the time delay between Src activation and FA disassembly was 1.2 min in cells seeded on low fibronectin concentration ([FN]) and 4.3 min in cells on high [FN]. CFIM further showed that the level of Src-FA coupling, as well as the time delay, was regulated by cell-matrix interactions, as a tight enzyme-structure coupling occurred in FA populations mediated by integrin αvβ3, but not in those by integrin α5β1. Therefore, different FA subpopulations have distinctive regulation mechanisms between their local kinase activity and structural FA dynamics.

  7. Analysis of the Temporal Organization of Sleep Spindles in the Human Sleep EEG Using a Phenomenological Modeling Approach

    Olbrich, Eckehard; Achermann, Peter


    The sleep electroencephalogram (EEG) is characterized by typical oscillatory patterns such as sleep spindles and slow waves. Recently, we proposed a method to detect and analyze these patterns using linear autoregressive models for short (≈ 1 s) data segments. We analyzed the temporal organization of sleep spindles and discuss to what extent the observed interevent intervals correspond to properties of stationary stochastic processes and whether additional slow processes, such as slow oscilla...

  8. Analysis of the temporal organization of sleep spindles in the human sleep EEG using a phenomenological modeling approach.

    Olbrich, E; Achermann, P


    The sleep electroencephalogram (EEG) is characterized by typical oscillatory patterns such as sleep spindles and slow waves. Recently, we proposed a method to detect and analyze these patterns using linear autoregressive models for short (≈ 1 s) data segments. We analyzed the temporal organization of sleep spindles and discuss to what extent the observed interevent intervals correspond to properties of stationary stochastic processes and whether additional slow processes, such as slow oscilla...

  9. Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up

    Nisa Azizun


    Full Text Available Spindle epithelial tumor with thymus-like differentiation (SETTLE is a rare malignant thyroid tumor showing thymic or related branchial pouch differentiation. The tumors are composed predominantly of spindle cells along with focal epithelial component and ductular formations. SETTLE occurs in young patients, with indolent growth and a tendency to develop delayed blood-borne metastases. We herein report two cases of SETTLE with a follow-up period of 64 months and 30 months, respectively.

  10. “Low-Fat” Pseudoangiomatous Spindle Cell Lipoma: A Rare Variant With Loss of 13q14 Region

    Forcucci, Jessica A.; Sugianto, Jessica Z.; Wolff, Daynna J.; Maize, John C.; Ralston, Jonathan S.


    Abstract: Spindle cell and pleomorphic lipoma constitute a spectrum of lipomatous lesions with characteristic clinical, morphologic, immunohistochemical, and molecular features. Multiple variants have been previously described including vascular, fibrous, plexiform, and those with significantly less fat termed “low-fat” and “fat-free” by Folpe. Cytogenetically, spindle cell lipomas frequently display monoallelic loss of 13q14 region, an abnormality also found in cellular angiofibroma and mamm...

  11. Measurement of Temperature Field for the Spindle of Machine Tool Based on Optical Fiber Bragg Grating Sensors

    Liu, Mingyao; Zhang, Erlong; Zhou, Zude; Tan, Yuegang; Liu, Yi


    The change of spindle temperature field is an important factor which influences machining precision. Many methods of spindle temperature field measurement have been proposed. However, most of the methods are based on the electric temperature sensors. There exist some defects (e.g., anti-interference, multiplexing, and stability capacity are poor). To increase the temperature sensitivity and reduce strain sensitivity of the bare Fiber Bragg Grating (FBG) sensor, a cassette packaged FBG sensor ...

  12. Method for Vibration Response Simulation and Sensor Placement Optimization of a Machine Tool Spindle System with a Bearing Defect

    Hongrui Cao; Linkai Niu; Zhengjia He


    Bearing defects are one of the most important mechanical sources for vibration and noise generation in machine tool spindles. In this study, an integrated finite element (FE) model is proposed to predict the vibration responses of a spindle bearing system with localized bearing defects and then the sensor placement for better detection of bearing faults is optimized. A nonlinear bearing model is developed based on Jones’ bearing theory, while the drawbar, shaft and housing are modeled as Timo...

  13. New Perspectives on Spontaneous Brain Activity: Dynamic Networks and Energy Matter

    Tozzi, Arturo; Zare, Marzieh; Benasich, April A.


    Spontaneous brain activity has received increasing attention as demonstrated by the exponential rise in the number of published article on this topic over the last 30 years. Such “intrinsic” brain activity, generated in the absence of an explicit task, is frequently associated with resting-state or default-mode networks (DMN)s. The focus on characterizing spontaneous brain activity promises to shed new light on questions concerning the structural and functional architecture of the brain and how they are related to “mind”. However, many critical questions have yet to be addressed. In this review, we focus on a scarcely explored area, specifically the energetic requirements and constraints of spontaneous activity, taking into account both thermodynamical and informational perspectives. We argue that the “classical” definitions of spontaneous activity do not take into account an important feature, that is, the critical thermodynamic energetic differences between spontaneous and evoked brain activity. Spontaneous brain activity is associated with slower oscillations compared with evoked, task-related activity, hence it exhibits lower levels of enthalpy and “free-energy” (i.e., the energy that can be converted to do work), thus supporting noteworthy thermodynamic energetic differences between spontaneous and evoked brain activity. Increased spike frequency during evoked activity has a significant metabolic cost, consequently, brain functions traditionally associated with spontaneous activity, such as mind wandering, require less energy that other nervous activities. We also review recent empirical observations in neuroscience, in order to capture how spontaneous brain dynamics and mental function can be embedded in a non-linear dynamical framework, which considers nervous activity in terms of phase spaces, particle trajectories, random walks, attractors and/or paths at the edge of the chaos. This takes us from the thermodynamic free-energy, to the realm

  14. Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

    Nishida M; Nakashima Y; Nishikawa T.


    Masaki Nishida,1 Yusaku Nakashima,2 Toru Nishikawa11Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, 2Medical Technology Research Laboratory, Research and Development Division, Medical Business Unit, Sony Corporation, Tokyo, JapanIntroduction: Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activit...

  15. Sleep spindles provide indirect support to the consolidation of emotional encoding contexts.

    Cairney, Scott A; Durrant, Simon J; Jackson, Rebecca; Lewis, Penelope A


    Emotional memories tend to be strengthened ahead of neutral memories during sleep-dependent consolidation. In recent work, however, we found that this is not the case when emotion pertains to the contextual features of a memory instead of its central constructs, suggesting that emotional contexts are influenced by distinct properties of sleep. We therefore examined the sleep-specific mechanisms supporting representations of emotional context and asked whether these differ to those already implicated in central emotional memory processing, such as rapid eye movement sleep (REM). Participants encoded neutral foreground images that were each associated with an emotionally negative or neutral background (context) image. Immediate and delayed tests for the emotionality of the foreground/background image association were separated by a 4-h consolidation period, which consisted of either total wakefulness or included a 2-h polysomnographically monitored nap. Although memory for negative contexts was not associated with REM, or any other parameter of sleep, sleep spindles (12-15 Hz) predicted increased forgetting and slowed response times for neutral contexts. Together with prior work linking spindles to emotional memory processing, our data may suggest that spindles provide multi-layered support to emotionally salient memories in sleep, with the nature of such effects depending on whether the emotionality of these memories pertains to their central or contextual features. Therefore, whereas spindles may mediate a direct strengthening of central emotional information, as suggested in prior work, they may also provide concurrent indirect support to emotional contexts by working to suppress non-salient neutral contexts. PMID:25223465

  16. Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis

    En-Ju Chou; Liang-Yi Hung; Chieh-Ju C. Tang; Wen-Bin Hsu; Hsin-Yi Wu; Pao-Chi Liao; Tang K. Tang


    CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. In...

  17. Mucinous tubular and spindle cell carcinoma of the kidney associated with tuberculosis

    Saloua Krichen Makni


    Full Text Available Mucinous tubular and spindle cell carcinomas (MTSCC are low-grade renal epi-thelial neoplasms with approximately 100 documented cases reported in the literature. We report a case of MTSCC in a 79-year-old patient in association with a renal tuberculosis infection that has never been reported. Further investigations are needed to determine the frequency and true prognosis of these tumors.

  18. Pax7 Shows Higher Satellite Cell Frequencies and Concentrations Within Intrafusal Fibers of Muscle Spindles

    Kirkpatrick, Lisa J.; Allouh, Mohammed Z.; Nightingale, Chantale N.; Devon, Heidi G.; Yablonka-Reuveni, Zipora; Rosser, Benjamin W. C.


    Intrafusal fibers within muscle spindles make up a small subpopulation of muscle fibers. These proprioceptive fibers differ from most extrafusal fibers because, even in maturity, their diameters remain small, and they retain expression of developmental myosins. Although both extrafusal and intrafusal fibers contain satellite cells (SCs), comparatively little is known about intrafusal SCs. Analyzing chicken fast-phasic posterior (PLD) and slow-tonic anterior (ALD) latissimus dorsi muscles, we ...

  19. A rare spindle-cell variant of non-Hodgkin's lymphoma of the mandible

    Srikant, N; Yinti, Shanmukha Raviteja; Baliga, Mohan; Kini, Hema


    A 64-year-old male farmer presented with a rapidly progressive swelling of the left mandible since 6 months. The swelling was firm to hard, diffuse, nontender, obliterating the vestibule with paresthesia of lower lip. The cone beam computed tomography imaging revealed an ill-defined, moth-eaten radiolucency with destruction of the buccal and lingual cortical plates. The rapid growth and aggressive behavior of the lesion coupled with guidance from the patient's previous reports from the incisional biopsy and fine needle aspiration cytology warranted a mandibular resection. Microscopic examination showed an encapsulated lesion situated in the connective tissue containing a mixture of proliferating spindle-shaped cells arranged in fascicles and round cells infiltrating into the connective tissue stroma and bone. The neoplastic cells exhibited atypical features such as pleomorphism, hyperchromatism and increased mitotic figures with noncleaved nuclei. A working diagnosis of a spindle-cell sarcoma was arrived at with various differentials provided such as fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, Langerhans cell histiocytosis and lymphoma and stating the need for immunohistochemistry to subtype the tumor. The neoplastic cells were negative for Van Gieson's stain and Masson's trichrome. Immunohistochemical analysis performed using desmin, smooth muscle actin, S-100 and CD1a in a bid to determine the phenotype of the tumor and rule out the previously stated differentials were all negative for the lesion. Lymphoid markers such as leukocyte common antigen and CD20 (cluster differentiation marker for B-cells) showed positivity in spindle-shaped cells as well as round cells indicating the tumor to be a lymphoproliferative lesion of B-cell type. A final diagnosis of “spindle-cell variant of non-Hodgkin's lymphoma” was rendered based on the immunohistochemical profile. PMID:27194875

  20. Detection of Potato spindle tuber viroid and Other Related Viroids by a DIG Labelled RNA Probe.

    Monger, Wendy A; Jeffries, Colin


    Viroids can cause diseases of considerable economic importance; in Europe the main concern is with pospiviroids that may affect the tomato and potato industries. Methods for detection are required that are both sensitive and robust. The detection method described here is a probe hybridization method with a commercially available digoxigenin (DIG) labelled full-length Potato spindle tuber viroid (PSTVd) RNA probe. This method detects PSTVd and all other known pospiviroids. PMID:25981260

  1. Linking Activity and Function to Ecosystem Dynamics in a Coastal Bacterioplankton Community

    Scott Michael Gifford


    Full Text Available For bacterial communities containing hundreds to thousands of distinct populations, connecting functional processes and environmental dynamics at high taxonomic resolution has remained challenging. Here we use the expression of ribosomal proteins (%RP as a proxy for in situ activity of 200 taxa within 20 metatranscriptomic samples in a coastal ocean time series encompassing both seasonal variability and diel dynamics. %RP patterns grouped the taxa into seven activity clusters with distinct profiles in functional gene expression and correlations with environmental gradients. Clusters 1-3 had their highest potential activity in the winter and fall, and included some of the most active taxa, while Clusters 4-7 had their highest potential activity in the spring and summer. Cluster 1 taxa were characterized by gene expression for motility and complex carbohydrate degradation (dominated by Gammaproteobacteria and Bacteroidetes, and Cluster 2 taxa by transcription of genes for amino acid and aromatic compound metabolism and aerobic anoxygenic phototrophy (Roseobacter. Other activity clusters were enriched in transcripts for proteorhodopsin and methylotrophy (Cluster 4; SAR11 and methylotrophs, photosynthesis and attachment (Clusters 5 and 7; Synechococcus, picoeukaryotes, Verucomicrobia, and Planctomycetes, and sulfur oxidation (Cluster 7; Gammaproteobacteria. The seasonal patterns in activity were overlain, and sometimes obscured, by large differences in %RP over shorter day-night timescales. Seventy-eight taxa, many of them heterotrophs, had a higher %RP activity index during the day than night, indicating strong diel activity at this coastal site. Emerging from these taxonomically- and time-resolved estimates of in situ microbial activity are predictions of specific ecological groupings of microbial taxa in a dynamic coastal environment.

  2. A case report of spindle cell myoepithelioma with extensive lipomatous metaplasia and thick collagen bundles in the submandibular gland.

    Kwon, Mi Jung; Kim, Hye Jeong; Park, Bumjung; Cho, Seong Jin; Shin, Hyung Sik; Park, Hye-Rim; Min, Soo Kee; Seo, Jinwon; Min, Kyueng-Whan; Nam, Eun Sook


    Spindle cell myoepithelioma with extensive lipomatous metaplasia and thick collagen bundles has not yet been described, and there are no published reports on its cytological appearance in fine-needle aspiration (FNA). A 49-year-old man presented with a painless mass in the right submandibular area that had been gradually enlarging for a period of 5 years. The cytologic smears showed fascicles of cohesive spindle cells as well as individual bland cells with bipolar naked nuclei in a fibrillary background. Brightly eosinophilic bundles were intermingled with spindle cells and fat-like vacuoles. The FNA results were suggestive of neurogenic tumor. Patient underwent submandibular gland resection. Grossly, the cut surface showed a well-encapsulated, yellowish-white, soft, elastic mass, measuring 2.8 × 1.9 × 1.5 cm. The tumor consisted of uniform bland spindle cells arranged in short fascicles admixed with adipocyte-like cells and transversing thick collagen bundles, which demonstrated immunoreactivity for myoepithelial markers and ultrastructural features characteristic of myoepithelial cells, suggesting the presence of lipomatous metaplasia. The FNA cytology of spindle cell myoepithelioma with extensive lipometaplasia mimicked that of neurogenic tumor or lipomatous mesenchymal tumor. This case represents the first description of submandibular gland myoepithelioma with lipometaplasia, which is characterized by the coexistence of spindle cells, collagen bundles, and fat-like vacuoles in a fibrillary background. Diagn. Cytopathol. 2016;44:764-769. © 2016 Wiley Periodicals, Inc. PMID:27307392

  3. The Mother Centriole Appendage Protein Cenexin Modulates Lumen Formation through Spindle Orientation.

    Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen


    Establishing apical-basal polarity is instrumental in the functional shaping of a solitary lumen within an acinus. By exploiting micropatterned slides, wound healing assays, and three-dimensional culture systems, we identified a mother centriole subdistal appendage protein, cenexin, as a critical player in symmetric lumen expansion through the control of microtubule organization. In this regard, cenexin was required for both centrosome positioning in interphase cells and proper spindle orientation during mitosis. In contrast, the essential mother centriole distal appendage protein CEP164 did not play a role in either process, demonstrating the specificity of subdistal appendages for these events. Importantly, upon closer examination we found that cenexin depletion decreased astral microtubule length, disrupted astral microtubule minus-end organization, and increased levels of the polarity protein NuMA at the cell cortex. Interestingly, spindle misorientation and NuMA mislocalization were reversed by treatment with a low dose of the microtubule-stabilizing agent paclitaxel. Taken together, these results suggest that cenexin modulates microtubule organization and stability to mediate spindle orientation. PMID:26948879

  4. Undifferentiated (Spindle Cell Pancreatic Carcinoma: A Case Report with Osteochondroid Differentiation

    Xing Wang


    Full Text Available Context Undifferentiated (spindle cell carcinomas of the pancreas are rare anaplastic variants of pancreatic ductal adenocarcinoma with a frequency of 2% of pancreatic exocrine tumors. Their clinicopathological features are limited and obtained by few previously case reports. We report a case of undifferentiated pancreatic carcinoma with a rare focal osteochondroid differentiation. Case report A sixty-six-year-old woman was admitted to our hospital for abdominal pain and nonspecific nausea for almost 40 days. Imaging studies revealed a well-defined cystic–solid mass with heterogeneous density involving the tail of the pancreas. We performed an en bloc distal pancreatectomy with splenectomy for radical excision, as well as regional lymphadenectomy. The resected specimen revealed a 4.0×5.0 cm exophytic clear-bordered neoplasm of the tail of the pancreas containing necrotic and calcified areas, without splenic invasion. The lymph node involvement was not detected (0/5 and the surgical margins were negative. Microscopy showed pleomorphism with giantcells, spindle-shaped cells with anaplasia, and osteochondroid differentiation. A diagnosis of undifferentiated (spindle cell carcinoma of the pancreas with focal osteochondroid differentiation was made. The patient declined chemotherapy and extended lymphadenectomy. She suffered from liver and lymph nodes metastasis 9 months after surgery, and she subsequently died 4 months later due to high tumor burden. Conclusions Undifferentiated pancreatic carcinoma with osteochondroid differentiation is rare but associated with extremely poor prognosis. It should be included in the differential diagnosis of pancreatic mass lesions.

  5. Mitotic Spindle Asymmetry: A Wnt/PCP-Regulated Mechanism Generating Asymmetrical Division in Cortical Precursors

    Delphine Delaunay


    Full Text Available The regulation of asymmetric cell division (ACD during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis. Imaging of spindle behavior and division outcome reveals that neurons preferentially arise from the larger-spindle pole. Mechanistically, SSA magnitude is controlled by Wnt7a and Vangl2, both members of the Wnt/planar cell polarity (PCP-signaling pathway, and relayed to the cell cortex by P-ERM proteins. In vivo, Vangl2 and P-ERM downregulation promotes early cell-cycle exit and prevents the proper generation of late-born neurons. Thus, SSA is a core component of ACD that is conserved in invertebrates and vertebrates and plays a key role in the tight spatiotemporal control of self-renewal and differentiation during mammalian corticogenesis.

  6. Primary histiocytic sarcoma arising in the head and neck with predominant spindle cell component

    Zhao XF


    Full Text Available Abstract This is the first case report of Histiocytic Sarcoma (HS with predominant spindle cell component occurring in the head and neck region of a 41-year-old man. The tumor was composed of sheets of large round to oval cells with pleomorphic vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. Multinucleated forms, numerous mitoses, and tumor necrosis were also noted. Sheets, fascicles, and whorls of spindle cells with spindled to ovoid vesicular nuclei, small to medium-sized distinct nucleoli, and eosinophilic cytoplasm were frequently observed. Immunohistochemical staining in the tumor cells was positive for CD163, CD68, lysozyme, CD45, and NSE. Focal expression of CD4 and S-100 was also noted. Electron microscopy demonstrated an abundance of lysosomes in the cytoplasm of tumor cells. Chromosome study revealed a 57–80 hyperdiploid [7]/46, XY [13] karyotype, including 3 to 4 copies of various chromosomes. The immunohistochemical and ultrastructural findings confirmed the diagnosis of HS.

  7. Dynamic correlation networks in human peroxisome proliferator-activated receptor-γ nuclear receptor protein.

    Fidelak, Jeremy; Ferrer, Silvia; Oberlin, Michael; Moras, Dino; Dejaegere, Annick; Stote, Roland H


    Peroxisome proliferator-activated receptor-γ nuclear receptor (PPAR-γ) belongs to the superfamily of nuclear receptor proteins that function as ligand-dependent transcription factors and plays a specific physiological role as a regulator of lipid metabolism. A number of experimental studies have suggested that allostery plays an important role in the functioning of PPAR-γ. Here we use normal-mode analysis of PPAR-γ to characterize a network of dynamically coupled amino acids that link physiologically relevant binding surfaces such as the ligand-dependent activation domain AF-2 with the ligand binding site and the heterodimer interface. Multiple calculations were done in both the presence and absence of the agonist rosiglitazone, and the differences in dynamics were characterized. The global dynamics of the ligand binding domain were affected by the ligand, and in particular, changes to the network of dynamically correlated amino acids were observed with only small changes in conformation. These results suggest that changes in dynamic couplings can be functionally significant with respect to the transmission of allosteric signals. PMID:20496064

  8. Multi-day activity scheduling reactions to planned activities and future events in a dynamic model of activity-travel behavior

    Nijland, Linda; Arentze, Theo; Timmermans, Harry


    Modeling multi-day planning has received scarce attention in activity-based transport demand modeling so far. However, new dynamic activity-based approaches are being developed at the current moment. The frequency and inflexibility of planned activities and events in activity schedules of individuals indicate the importance of incorporating those pre-planned activities in the new generation of dynamic travel demand models. Elaborating and combining previous work on event-driven activity generation, the aim of this paper is to develop and illustrate an extension of a need-based model of activity generation that takes into account possible influences of pre-planned activities and events. This paper describes the theory and shows the results of simulations of the extension. The simulation was conducted for six different activities, and the parameter values used were consistent with an earlier estimation study. The results show that the model works well and that the influences of the parameters are consistent, logical, and have clear interpretations. These findings offer further evidence of face and construct validity to the suggested modeling approach.

  9. Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer.

    Köster, Darius Vasco; Husain, Kabir; Iljazi, Elda; Bhat, Abrar; Bieling, Peter; Mullins, R Dyche; Rao, Madan; Mayor, Satyajit


    The surface of a living cell provides a platform for receptor signaling, protein sorting, transport, and endocytosis, whose regulation requires the local control of membrane organization. Previous work has revealed a role for dynamic actomyosin in membrane protein and lipid organization, suggesting that the cell surface behaves as an active composite composed of a fluid bilayer and a thin film of active actomyosin. We reconstitute an analogous system in vitro that consists of a fluid lipid bilayer coupled via membrane-associated actin-binding proteins to dynamic actin filaments and myosin motors. Upon complete consumption of ATP, this system settles into distinct phases of actin organization, namely bundled filaments, linked apolar asters, and a lattice of polar asters. These depend on actin concentration, filament length, and actin/myosin ratio. During formation of the polar aster phase, advection of the self-organizing actomyosin network drives transient clustering of actin-associated membrane components. Regeneration of ATP supports a constitutively remodeling actomyosin state, which in turn drives active fluctuations of coupled membrane components, resembling those observed at the cell surface. In a multicomponent membrane bilayer, this remodeling actomyosin layer contributes to changes in the extent and dynamics of phase-segregating domains. These results show how local membrane composition can be driven by active processes arising from actomyosin, highlighting the fundamental basis of the active composite model of the cell surface, and indicate its relevance to the study of membrane organization. PMID:26929326

  10. Thermal ignition revisited with molecular dynamics: role of fluctuations in activated collisions

    Sirmas, Nick


    The problem of thermal ignition in a homogeneous gas is revisited from a molecular dynamics perspective. The simple model assumes reactive particles of type A and B in a fixed domain that react to form type C products if an activation threshold for impact is surpassed. Such a reaction liberates kinetic energy to the product particles, representative of the heat release. The results are compared with those obtained from the continuum description with the reaction rate evaluated from kinetic theory assuming local thermodynamic equilibrium and Maxwell-Boltzmann statistics, in order to assess the role played by molecular fluctuations. Results show that at low activation energies, the ignition time obtained from the molecular dynamics is independent of domain size, with values exceeding what is expected from the continuum model for all values of heat release. The ignition time was found dependent on domain size for larger activation energies. Small domains of $N=100$ particles yielded longer ignition delays than p...

  11. Dynamic characteristics of Semi-active Hydraulic Engine Mount Based on Fluid-Structure Interaction FEA

    Tian Jiande


    Full Text Available A kind of semi-active hydraulic engine mount is studied in this paper. After careful analysis of its structure and working principle, the FEA simulation of it was divided into two cases. One is the solenoid valve is open, so the air chamber connects to the atmosphere, and Fluid-Structure Interaction was used. Another is the solenoid valve is closed, and the air chamber has pressure, so Fluid-Structure-Gas Interaction was used. The test of this semi-active hydraulic engine mount was carried out to compare with the simulation results, and verify the accuracy of the model. Then the dynamic characteristics-dynamic stiffness and damping angle were analysed by simulation and test. This paper provides theoretical support for the development and optimization of the semi-active hydraulic engine mount.

  12. Structural Dynamics Experimental Activities in Ultra-Lightweight and Inflatable Space Structures

    Pappa, Richard S.; Lassiter, John O.; Ross, Brian P.


    This paper reports recently completed structural dynamics experimental activities with new ultra-lightweight and inflatable space structures (a.k.a., "Gossamer" spacecraft) at NASA Langley Research Center, NASA Marshall Space Flight Center, and NASA Goddard Space Flight Center. Nine aspects of this work are covered: 1) inflated, rigidized tubes, 2) active control experiments, 3) photogrammetry, 4) laser vibrometry, 5) modal tests of inflatable structures, 6) in-vacuum modal tests, 7) tensioned membranes, 8) deployment tests, and 9) flight experiment support. Structural dynamics will play a major role in the design and eventually in-space deployment and performance of Gossamer spacecraft. Experimental research and development such as this is required to validate new analysis methods. The activities discussed in the paper are pathfinder accomplishments. conducted on unique components and prototypes of future spacecraft systems.

  13. On Application Of Langevin Dynamics In Logarithmic Potential To Model Ion Channel Gate Activity.

    Wawrzkiewicz-Jałowiecka, Agata; Borys, Przemysław; Grzywna, Zbigniew J


    We model the activity of an ion channel gate by Langevin dynamics in a logarithmic potential. This approach enables one to describe the power-law dwell-time distributions of the considered system, and the long-term correlations between the durations of the subsequent channel states, or fractal scaling of statistical characteristics of the gate's movement with time. Activity of an ion channel gate is described as an overdamped motion of the reaction coordinate in a confining logarithmic potential, which ensures great flexibility of the model. Depending on the chosen parameters, it allows one to reproduce many types of gate dynamics within the family of non-Markovian, anomalous conformational diffusion processes. In this study we apply the constructed model to largeconductance voltage and Ca2+-activated potassium channels (BKCa). The interpretation of model assumptions and parameters is provided in terms of this biological system. Our results show good agreement with the experimental data. PMID:26317442

  14. Multifractal features of magnetospheric dynamics and their dependence on solar activity

    Gopinath, Sumesh


    In the present study, novel wavelet leaders (WL) based multifractal analysis has been used to get a better knowledge of the self-organization phenomena inherent in complex magnetospheric dynamics during disturbance and quiescent periods, focusing mainly on the intermittent features of auroral electrojet (AE) index. The results derived from the analysis certainly exhibit the phase transition property of magnetosphere system with respect to variabilities in the driving conditions. By using the novel WL method, solar activity dependence/independence of intermittency of magnetospheric proxies such as AE, SYM-H and Dst indices have been compared. The results indicate that the multifractality of AE index does not follow the solar activity cycle while intermittent features of SYM-H and Dst indices show high degree of solar activity dependence. This shows that along with the external solar wind perturbations, certain complex phenomena of internal origin also significantly modulate the dynamics of geomagnetic fluctuations in the auroral region.

  15. [Factors Affecting the Dynamics of Circadian Activity of Frit Flies Meromyza saltatrix (L) (Diptera: Chloropidae)].

    Safonkin, A F; Triselyova, T A; Yazchuk, A A; Akent'eva, N A


    The dynamics of circadian activity in adult frit flies of the Holarctic species Meromyza saltatrix (L) from Mongolian, Moscow, and Polish populations was studied. Synchronous peaks of activity were revealed with the periodicity multiple of three-four hours, which may depend on the level of light. The direct effect of temperature and humidity on the activity of flies outside the optimal values of these factors was found. It was detected that the peak of adult emergence falls on the beginning of a general increase in the abundance of flies, which indicates constant rejuvenation of the population. The sex ratio is close to 1, but the emergence of males and females is in antiphase. The synchronization of peaks of circadian activity in the populations from different regions confirms the presence of a circadian rhythm of activity. The rhythm synchronizing the reproductive activity of adults was found to be modified by the photoperiod under the optimum conditions of temperature and humidity. PMID:26852486

  16. Dynamic Structural Changes During Complement C3 Activation Analyzed by Hydrogen/Deuterium Exchange Mass Spectrometry

    Schuster, Michael C.; Ricklin, Daniel; Papp, Krisztián; Molnar, Kathleen S.; Coales, Stephen J.; Hamuro, Yoshitomo; Sfyroera, Georgia; Chen, Hui; Winters, Michael S; Lambris, John D.


    Proteolytic cleavage of component C3 to C3b is a central step in the activation of complement. Whereas C3 is largely biologically inactive, C3b is directly involved in various complement activities. While the recently described crystal structures of C3 and C3b provide a molecular basis of complement activation, they do not reflect the dynamic changes that occur in solution. In addition, the available C3b structures diverge in some important aspects. Here we have utilized hydrogen/deuterium ex...

  17. Phase Behavior of Active Swimmers in Depletants: Molecular Dynamics and Integral Equation Theory

    Das, Subir K.; Egorov, Sergei A.; Trefz, Benjamin; Virnau, Peter; Binder, Kurt


    We study the structure and phase behavior of a binary mixture where one of the components is self-propelling in nature. The interparticle interactions in the system are taken from the Asakura-Oosawa model for colloid-polymer mixtures for which the phase diagram is known. In the current model version, the colloid particles are made active using the Vicsek model for self-propelling particles. The resultant active system is studied by molecular dynamics methods and integral equation theory. Both methods produce results consistent with each other and demonstrate that the Vicsek model-based activity facilitates phase separation, thus, broadening the coexistence region.

  18. Tourist activated networks: Implications for dynamic bundling and en-route recommendations

    Zach, Florian; Gretzel, Ulrike


    This article discusses tourist-activated networks as a concept to inform technological applications supporting dynamic bundling and en route recommendations. Empirical data were collected from travelers who visited a regional destination in the US and then analyzed with respect to its network...... structure. The results indicate that the tourist-activated network for the destination is rather sparse and that there are clearly differences in core and peripheral nodes. The findings illustrate the structure of a tourist-activated network and provide implications for technology design and tourism...

  19. Light Bridge in a Developing Active Region. I. Observation of Light Bridge and its Dynamic Activity Phenomena

    Toriumi, Shin; Cheung, Mark C M


    Light bridges, the bright structures that divide the umbra of sunspots and pores into smaller pieces, are known to produce wide variety of activity events in solar active regions (ARs). It is also known that the light bridges appear in the assembling process of nascent sunspots. The ultimate goal of this series of papers is to reveal the nature of light bridges in developing ARs and the occurrence of activity events associated with the light bridge structures from both observational and numerical approaches. In this first paper, exploiting the observational data obtained by Hinode, IRIS, and Solar Dynamics Observatory (SDO), we investigate the detailed structure of the light bridge in NOAA AR 11974 and its dynamic activity phenomena. As a result, we find that the light bridge has a weak, horizontal magnetic field, which is transported from the interior by large-scale convective upflow and is surrounded by strong, vertical fields of adjacent pores. In the chromosphere above the bridge, a transient brightening ...

  20. Convergence dynamics of the Bak Sneppen model: Activity rate and waiting time distribution

    Tirnakli, Ugur; Lyra, Marcelo L.


    In this work, we study the convergence dynamics of two independent random configurations of the Bak-Sneppen model of self-organized criticality evolving under the same external noise. A recently proposed measure of the Hamming distance which considers the minimum difference between displaced configurations is used. The displacement evolves in time intermittently. We compute the jump activity rate and waiting time distribution and report on their asymptotic power-law scaling which characterizes the slow relaxation and the absence of typical length and time scales typical of critical dynamical systems.

  1. Spindle-F Is the Central Mediator of Ik2 Kinase-Dependent Dendrite Pruning in Drosophila Sensory Neurons.

    Lin, Tzu; Pan, Po-Yuan; Lai, Yu-Ting; Chiang, Kai-Wen; Hsieh, Hsin-Lun; Wu, Yi-Ping; Ke, Jian-Ming; Lee, Myong-Chol; Liao, Shih-Sian; Shih, Hsueh-Tzu; Tang, Chiou-Yang; Yang, Shi-Bing; Cheng, Hsu-Chen; Wu, June-Tai; Jan, Yuh-Nung; Lee, Hsiu-Hsiang


    During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F) that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons. PMID:26540204

  2. Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy.

    Tan, Chye Ling; Teissier, Sébastien; Gunaratne, Jayantha; Quek, Ling Shih; Bellanger, Sophie


    The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have anti-oncogenic properties. Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. While BUBR1 silencing rescues the mitotic phenotype induced by E2, p53 silencing or presence of E6/E7 (inactivating p53 and increasing BUBR1 levels respectively) both amplify it. This work pinpoints E2 as a key protein in the initiation of HPV-induced cervical cancer and identifies the SAC as a target for oncogenic pathogens. Moreover, our results suggest a role of p53 in regulating the mitotic process itself and highlight SAC over-activation in a p53-negative context as a highly pathogenic event. PMID:25789401

  3. Single, competitive, and dynamic adsorption on activated carbon of compounds used as plasticizers and herbicides.

    Abdel daiem, Mahmoud M; Rivera-Utrilla, José; Sánchez-Polo, Manuel; Ocampo-Pérez, Raúl


    The main aim of this study was to investigate the single, competitive, and dynamic adsorption of phthalic acid (PA), bisphenol A (BPA), diphenolic acid (DPA), 2,4-dichlorophenoxy-acetic acid (2,4-D), and 4-chloro-2-methylphenoxyacetic acid (MCPA) on two activated carbons with different chemical natures and similar textural characteristics. The adsorption mechanism was also elucidated by analyzing the influence of solution pH and ionic strength. The activated carbons demonstrated high adsorption capacity to remove all micropollutants due to the presence of active sites on their surfaces, which increase dispersive interactions between the activated carbon graphene layers and the aromatic ring of pollutants. The adsorption capacity of the activated carbons increased in the order: DPAdynamic regime, the amount of pollutant adsorbed was much higher for PA, followed by DPA, and was approximately similar for BPA, 2,4-D, and MCPA. Finally, the amount of BPA and DPA adsorbed on activated carbon decreased by around 50% and 70% in the presence of DPA and BPA, respectively, indicating that both compounds are adsorbed on the same adsorption sites of the activated carbon. PMID:26282767

  4. N-terminus-modified Hec1 suppresses tumour growth by interfering with kinetochore-microtubule dynamics.

    Orticello, M; Fiore, M; Totta, P; Desideri, M; Barisic, M; Passeri, D; Lenzi, J; Rosa, A; Orlandi, A; Maiato, H; Del Bufalo, D; Degrassi, F


    Mitotic proteins are attractive targets to develop molecular cancer therapeutics due to the intimate interdependence between cell proliferation and mitosis. In this work, we have explored the therapeutic potential of the kinetochore (KT) protein Hec1 (Highly Expressed in Cancer protein 1) as a molecular target to produce massive chromosome missegregation and cell death in cancer cells. Hec1 is a constituent of the Ndc80 complex, which mediates KT-microtubule (MT) attachments at mitosis and is upregulated in various cancer types. We expressed Hec1 fused with enhanced green fluorescent protein (EGFP) at its N-terminus MT-interaction domain in HeLa cells and showed that expression of this modified Hec1, which localized at KTs, blocked cell proliferation and promoted apoptosis in tumour cells. EGFP-Hec1 was extremely potent in tumour cell killing and more efficient than siRNA-induced Hec1 depletion. In striking contrast, normal cells showed no apparent cell proliferation defects or cell death following EGFP-Hec1 expression. Live-cell imaging demonstrated that cancer cell death was associated with massive chromosome missegregation within multipolar spindles after a prolonged mitotic arrest. Moreover, EGFP-Hec1 expression was found to increase KT-MT attachment stability, providing a molecular explanation for the abnormal spindle architecture and the cytotoxic activity of this modified protein. Consistent with cell culture data, EGFP-Hec1 expression was found to strongly inhibit tumour growth in a mouse xenograft model by disrupting mitosis and inducing multipolar spindles. Taken together, these findings demonstrate that stimulation of massive chromosome segregation defects can be used as an anti-cancer strategy through the activation of mitotic catastrophe after a multipolar mitosis. Importantly, this study represents a clear proof of concept that targeting KT proteins required for proper KT-MT attachment dynamics constitutes a powerful approach in cancer therapy. PMID

  5. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco


    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  6. Colloidal particle adsorption at liquid interfaces: capillary driven dynamics and thermally activated kinetics.

    Rahmani, Amir M; Wang, Anna; Manoharan, Vinothan N; Colosqui, Carlos E


    The adsorption of single colloidal microparticles (0.5-1 μm radius) at a water-oil interface has been recently studied experimentally using digital holographic microscopy [Kaz et al., Nat. Mater., 2012, 11, 138-142]. An initially fast adsorption dynamics driven by capillary forces is followed by an unexpectedly slow relaxation to equilibrium that is logarithmic in time and can span hours or days. The slow relaxation kinetics has been attributed to the presence of surface "defects" with nanoscale dimensions (1-5 nm) that induce multiple metastable configurations of the contact line perimeter. A kinetic model considering thermally activated transitions between such metastable configurations has been proposed [Colosqui et al., Phys. Rev. Lett., 2013, 111, 028302] to predict both the relaxation rate and the crossover point to the slow logarithmic regime. However, the adsorption dynamics observed experimentally before the crossover point has remained unstudied. In this work, we propose a Langevin model that is able to describe the entire adsorption process of single colloidal particles by considering metastable states produced by surface defects and thermal motion of the particle and liquid interface. Invoking the fluctuation dissipation theorem, we introduce a drag term that considers significant dissipative forces induced by thermal fluctuations of the liquid interface. Langevin dynamics simulations based on the proposed adsorption model yield close agreement with experimental observations for different microparticles, capturing the crossover from (fast) capillary driven dynamics to (slow) thermally activated kinetics. PMID:27373956

  7. A nuclear circularity-based classifier for diagnostic distinction of desmoplastic from spindle cell melanoma in digitized histological images

    Manuel Schöchlin


    Full Text Available Context: Distinction of spindle cell melanoma (SM and desmoplastic melanoma (DM is clinically important due to differences in metastatic rate and prognosis; however, histological distinction is not always straightforward. During a routine review of cases, we noted differences in nuclear circularity between SM and DM. Aim: The primary aim in our study was to determine whether these differences in nuclear circularity, when assessed using a basic ImageJ-based threshold extraction, can serve as a diagnostic classifier to distinguish DM from SM. Settings and Design: Our retrospective analysis of an established patient cohort (SM n = 9, DM n = 9 was employed to determine discriminatory power. Subjects and Methods: Regions of interest (total n = 108; 6 images per case were selected from scanned H and E-stained histological sections, and nuclear circularity was extracted and quantified by computational image analysis using open source tools (plugins for ImageJ. Statistical Analysis: Using analysis of variance, t-tests, and Fisher′s exact tests, we compared extracted quantitative shape measures; statistical significance was defined as P < 0.05. Results: Classifying circularity values into four shape categories (spindled, elongated, oval, round demonstrated significant differences in the spindled and round categories. Paradoxically, DM contained more spindled nuclei than SM (P = 0.011 and SM contained more round nuclei than DM (P = 0.026. Performance assessment using a combined shape-classification of the round and spindled fractions showed 88.9% accuracy and a Youden index of 0.77. Conclusions: Spindle cell melanoma and DM differ significantly in their nuclear morphology with respect to fractions of round and spindled nuclei. Our study demonstrates that quantifying nuclear circularity can be used as an adjunct diagnostic tool for distinction of DM and SM.

  8. Coordinated Action of Fast and Slow Reserves for Optimal Sequential and Dynamic Emergency Reserve Activation

    Salkuti, Surender Reddy; Bijwe, P. R.; Abhyankar, A. R.


    This paper proposes an optimal dynamic reserve activation plan after the occurrence of an emergency situation (generator/transmission line outage, load increase or both). An optimal plan is developed to handle the emergency situation, using coordinated action of fast and slow reserves, for secure operation with minimum overall cost. This paper considers the reserves supplied by generators (spinning reserves) and loads (demand-side reserves). The optimal backing down of costly/fast reserves and bringing up of slow reserves in each sub-interval in an integrated manner is proposed. The simulation studies are performed on IEEE 30, 57 and 300 bus test systems to demonstrate the advantage of proposed integrated/dynamic reserve activation plan over the conventional/sequential approach.

  9. Lack of Negative Correlation in Glucose Dynamics by Nonexercise Activity Thermogenesis Restriction in Healthy Adults

    Ogata, Hitomi; NAKAMURA, KAZUTERU; Sato, Maki; Tokuyama, Kumpei; Nagasaka, Shoichiro; Ebine, Naoyuki; Kiyono, Ken; Yamamoto, Yoshiharu


    Introduction: Recently, nonexercise activity thermogenesis (NEAT) has been highlighted for its ability to prevent weight gain and obesity. It has also been shown that the long-range negative autocorrelation of glucose dynamics, considered to reflect long-term blood glucose controllability, breaks down in patients with diabetes.Purpose: The purpose of this study was to clarify the effect of restricted NEAT on the glycemic profile and/or control characterized by glucose autocorrelation.Methods:...

  10. Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity.

    Marc Breit; Michael Netzer; Weinberger, Klaus M.; Christian Baumgartner


    The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured t...

  11. Communication in Joint Activity : Investigating Teams’ Communication Pattern in a Dynamic Decision Making Environment

    Baroutsi, Nicoletta


    The complexity in the world is continuously increasing. Teams are faced with imperfect information in uncertain, dynamic, and time critical environments as they strive to make the right decisions, not just as individuals, but as a team. In this joint activity the members choreograph their actions and synchronize their behavior through the use of communication. Communication is the predominant form of interaction within teams – it is not only a window into team cognition – it is an externalize...

  12. Brassica spp cover crop affects soil microbial activity, carbon and nitrogen nutrient dynamics

    Marinari, S.; Papp, R.; Marabottini, R.; Moscatelli, M. C.


    A general positive effect of Brassica on soil microbial biomass and its activity was observed at all European sites in no tilled soil at both sampling date. Conversely, Brassica under tillage may produce a negative effect on biochemical properties after CC suppression. The effect of Brassica on C and N dynamics differed among the european sites when soil was tilled. These preliminary results establish the bases for the evaluation of the interaction between the pedoclimatic conditions and Bras...

  13. Identification of Essential Cannabinoid-binding Domains: STRUCTURAL INSIGHTS INTO EARLY DYNAMIC EVENTS IN RECEPTOR ACTIVATION*

    Shim, Joong-Youn; Bertalovitz, Alexander C.; Kendall, Debra A.


    The classical cannabinoid agonist HU210, a structural analog of (−)-Δ9-tetrahydrocannabinol, binds to brain cannabinoid (CB1) receptors and activates signal transduction pathways. To date, an exact molecular description of the CB1 receptor is not yet available. Utilizing the minor binding pocket of the CB1 receptor as the primary ligand interaction site, we explored HU210 binding using lipid bilayer molecular dynamics (MD) simulations. Among the potential ligand contact residues, we identifie...

  14. Community Structure and Activity Dynamics of Nitrifying Bacteria in a Phosphate-Removing Biofilm

    Gieseke, Armin; Purkhold, Ulrike; Wagner, Michael; Amann, Rudolf; Schramm, Andreas


    The microbial community structure and activity dynamics of a phosphate-removing biofilm from a sequencing batch biofilm reactor were investigated with special focus on the nitrifying community. O2, NO2−, and NO3− profiles in the biofilm were measured with microsensors at various times during the nonaerated-aerated reactor cycle. In the aeration period, nitrification was oxygen limited and restricted to the first 200 μm at the biofilm surface. Additionally, a delayed onset of nitrification aft...

  15. Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

    Li, Jun; Li, Neng-Ping; GU Yong-feng; Yang, Xin; LU Xiao-bing; CONG Jian-nong; Ling, Yun; TANG Jiang-an; Yuan, Xiao-yan; Wang, Hu


    【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment), ulinastain group (25 cas...

  16. Active vibration control of a rotor-bearing system based on dynamic stiffness

    Andrés Blanco Ortega; Francisco Beltrán Carbajal; Gerardo Silva Navarro; Marco Antonio Oliver Salazar


    This paper presents an active vibration control scheme to reduce unbalance induced synchronous vibration in rotorbearing systems supported on two ball bearings, one of which can be automatically moved to control the effective rotor length and, as an immediate consequence, the rotor stiffness. This dynamic stiffness control scheme, based on frequency analysis, speed control and acceleration scheduling, is used to avoid resonant vibration of a rotor system when it passes (runup or coast down) t...

  17. Chaotic Temperatures vs Coefficients of Thermodynamic Activity The Advantage of the Method of Chemical Dynamics

    Zilbergleyt, B


    The article compares traditional coefficients of thermodynamic activity as a parameter related to individual chemical species to newly introduced reduced chaotic temperatures as system characteristics, both regarding their usage in thermodynamic simulation of open chemical systems. Logical and mathematical backgrounds of both approaches are discussed. It is shown that usage of reduced chaotic temperatures and the Method of Chemical Dynamics to calculate chemical and phase composition in open chemical systems is much less costly, easier to perform and potentially leads to better precision.

  18. Assessment of CO₂ adsorption capacity on activated carbons by a combination of batch and dynamic tests.

    Balsamo, Marco; Silvestre-Albero, Ana; Silvestre-Albero, Joaquín; Erto, Alessandro; Rodríguez-Reinoso, Francisco; Lancia, Amedeo


    In this work, batch and dynamic adsorption tests are coupled for an accurate evaluation of CO2 adsorption performance of three different activated carbons (AC) obtained from olive stones by chemical activation followed by physical activation with CO2 at varying times (i.e., 20, 40, and 60 h). Kinetic and thermodynamic CO2 adsorption tests from simulated flue gas at different temperatures and CO2 pressures are carried out under both batch (a manometric equipment operating with pure CO2) and dynamic (a lab-scale fixed-bed column operating with a CO2/N2 mixture) conditions. The textural characterization of the AC samples shows a direct dependence of both micropore and ultramicropore volume on the activation time; hence, AC60 has the higher contribution. The adsorption tests conducted at 273 and 293 K showed that when CO2 pressure is lower than 0.3 bar, the lower the activation time, the higher CO2 adsorption capacity; a ranking of ω(eq)(AC20) > ω(eq)(AC40) > ω(eq)(AC60) can be exactly defined when T = 293 K. This result is likely ascribed to the narrower pore size distribution of the AC20 sample, whose smaller pores are more effective for CO2 capture at higher temperature and lower CO2 pressure, the latter representing operating conditions of major interest for decarbonation of flue gas effluent. Moreover, the experimental results obtained from dynamic tests confirm the results derived from the batch tests in terms of CO2 adsorption capacity. It is important to highlight the fact that the adsorption of N2 on the synthesized AC samples can be considered to be negligible. Finally, the importance of proper analysis for data characterization and adsorption experimental results is highlighted for the correct assessment of the CO2 removal performance of activated carbons at different CO2 pressures and operating temperatures. PMID:24784997

  19. Dynamics of inert spheres in active suspensions of micro-rotors.

    Yeo, Kyongmin; Lushi, Enkeleida; Vlahovska, Petia M


    Inert particles suspended in active fluids of self-propelled particles are known to often exhibit enhanced diffusion and novel coherent structures. Here we numerically investigate the dynamical behavior and self-organization in a system consisting of passive and actively rotating spheres of the same size. The particles interact through direct collisions and the fluid flows generated as they move. In the absence of passive particles, three states emerge in a binary mixture of spinning spheres depending on particle fraction: a dilute gas-like state where the rotors move chaotically, a phase-separated state where like-rotors move in lanes or vortices, and a jammed state where crystals continuously assemble, melt and move (K. Yeo, E. Lushi, and P. M. Vlahovska, Phys. Rev. Lett., 2015, 114, 188301). Passive particles added to the rotor suspension modify the system dynamics and pattern formation: while states identified in the pure active suspension still emerge, they occur at different densities and mixture proportions. The dynamical behavior of the inert particles is also non-trivially dependent on the system composition. PMID:27265340

  20. Sustained neural activity to gaze and emotion perception in dynamic social scenes.

    Ulloa, José Luis; Puce, Aina; Hugueville, Laurent; George, Nathalie


    To understand social interactions, we must decode dynamic social cues from seen faces. Here, we used magnetoencephalography (MEG) to study the neural responses underlying the perception of emotional expressions and gaze direction changes as depicted in an interaction between two agents. Subjects viewed displays of paired faces that first established a social scenario of gazing at each other (mutual attention) or gazing laterally together (deviated group attention) and then dynamically displayed either an angry or happy facial expression. The initial gaze change elicited a significantly larger M170 under the deviated than the mutual attention scenario. At around 400 ms after the dynamic emotion onset, responses at posterior MEG sensors differentiated between emotions, and between 1000 and 2200 ms, left posterior sensors were additionally modulated by social scenario. Moreover, activity on right anterior sensors showed both an early and prolonged interaction between emotion and social scenario. These results suggest that activity in right anterior sensors reflects an early integration of emotion and social attention, while posterior activity first differentiated between emotions only, supporting the view of a dual route for emotion processing. Altogether, our data demonstrate that both transient and sustained neurophysiological responses underlie social processing when observing interactions between others. PMID:23202662