The structure of the actin-smooth muscle myosin motor domain complex in the rigor state.

Science.gov (United States)

Banerjee, Chaity; Hu, Zhongjun; Huang, Zhong; Warrington, J Anthony; Taylor, Dianne W; Trybus, Kathleen M; Lowey, Susan; Taylor, Kenneth A

2017-12-01

Myosin-based motility utilizes catalysis of ATP to drive the relative sliding of F-actin and myosin. The earliest detailed model based on cryo-electron microscopy (cryoEM) and X-ray crystallography postulated that higher actin affinity and lever arm movement were coupled to closure of a feature of the myosin head dubbed the actin-binding cleft. Several studies since then using crystallography of myosin-V and cryoEM structures of F-actin bound myosin-I, -II and -V have provided details of this model. The smooth muscle myosin II interaction with F-actin may differ from those for striated and non-muscle myosin II due in part to different lengths of important surface loops. Here we report a ∼6 Å resolution reconstruction of F-actin decorated with the nucleotide-free recombinant smooth muscle myosin-II motor domain (MD) from images recorded using a direct electron detector. Resolution is highest for F-actin and the actin-myosin interface (3.5-4 Å) and lowest (∼6-7 Å) for those parts of the MD at the highest radius. Atomic models built into the F-actin density are quite comparable to those previously reported for rabbit muscle actin and show density from the bound ADP. The atomic model of the MD, is quite similar to a recently published structure of vertebrate non-muscle myosin II bound to F-actin and a crystal structure of nucleotide free myosin-V. Larger differences are observed when compared to the cryoEM structure of F-actin decorated with rabbit skeletal muscle myosin subfragment 1. The differences suggest less closure of the 50 kDa domain in the actin bound skeletal muscle myosin structure. Copyright © 2017 Elsevier Inc. All rights reserved.

Orientation of spin-labeled light chain 2 of myosin heads in muscle fibers.

Science.gov (United States)

Arata, T

1990-07-20

Electron paramagnetic resonance (e.p.r.) spectroscopy has been used to monitor the orientation of spin labels attached rigidly to a reactive SH residue on the light chain 2 (LC2) of myosin heads in muscle fibers. e.p.r. spectra from spin-labeled myosin subfragment-1 (S1), allowed to diffuse into unlabeled rigor (ATP-free) fibers, were roughly approximated by a narrow angular distribution of spin labels centered at 66 degrees relative to the fiber axis, indicating a uniform orientation of S1 bound to actin. On the other hand, spectra from spin-labeled heavy meromyosin (HMM) were roughly approximated by two narrow angular distributions centered at 42 degrees and 66 degrees, suggesting that the LC2 domains of the two HMM heads have different orientations. In contrast to S1 or HMM, the spectra from rigor fibers, in which LC2 of endogenous myosin heads was labeled, showed a random orientation which may be due to distortion imposed by the structure of the filament lattice and the mismatch of the helical periodicities of the thick and thin filaments. However, spectra from the fibers in the presence of ATP analog 5'-adenylyl imidodiphosphate (AMPPNP) were approximated by two narrow angular distributions similar to those obtained with HMM. Thus, AMPPNP may cause the LC2 domain to be less flexible and/or the S2 portion to be more flexible, so as to release the distortion of the LC2 domain and make it return to its natural position. At high ionic strength, AMPPNP disoriented the spin labels as ATP did under relaxing conditions, suggesting that the myosin head is detached from and/or weakly (flexibly) attached to a thin filament.

The effects of transverse rotation angle on compression and effective lever arm of prosthetic feet during simulated stance.

Science.gov (United States)

Major, Matthew J; Howard, David; Jones, Rebecca; Twiste, Martin

2012-06-01

Unlike sagittal plane prosthesis alignment, few studies have observed the effects of transverse plane alignment on gait and prosthesis behaviour. Changes in transverse plane rotation angle will rotate the points of loading on the prosthesis during stance and may alter its mechanical behaviour. This study observed the effects of increasing the external transverse plane rotation angle, or toe-out, on foot compression and effective lever arm of three commonly prescribed prosthetic feet. The roll-over shape of a SACH, Flex and single-axis foot was measured at four external rotation angle conditions (0°, 5°, 7° and 12° relative to neutral). Differences in foot compression between conditions were measured as average distance between roll-over shapes. Increasing the transverse plane rotation angle did not affect foot compression. However, it did affect the effective lever arm, which was maximized with the 5° condition, although differences between conditions were small. Increasing the transverse plane rotation angle of prosthetic feet by up to 12° beyond neutral has minimal effects on their mechanical behaviour in the plane of walking progression during weight-bearing.

Physiological evaluation of a newly designed lever mechanism for wheelchairs

NARCIS (Netherlands)

van der Woude, L H; Veeger, DirkJan (H. E. J.); de Boer, Y; Rozendal, R H

1993-01-01

Lever-propelled wheelchairs have been described as more efficient and less physically demanding than hand-rim-propelled wheelchairs. To evaluate a newly designed lever mechanism (MARC) in both one- and two-arm use, a series of wheelchair exercise tests were performed on a motor-driven treadmill.

A technique for the calibration of Andrade-Chalmers cam levers used on creep tests

International Nuclear Information System (INIS)

Mendoza, A.; Salazar, A.; Morales, A.; Montemayor-Aldrete, M.

1994-01-01

In this work we report the analysis of typical errors arising from an Andrade-Chalmers lever cam, used as machine for mechanical constant stress tests. A procedure to obtain the magnitude of the applied stress as a function of the rotation of the lever arm was developed by used a mechanism which allow us to simulate the sample deformation. The used physical mechanism involves LVDT and Load Cell transducers. The characteristic parameters of the lever arm were founded using a least squares criterion procedure on the digitalized values of transducers signals. The departure existing between an actual lever and ideal one was fully analyzed. (Author) 18 refs

Fluorescent modification and orientation of myosin sulfhydryl 2 in skeletal muscle fibers

International Nuclear Information System (INIS)

Ajtai, K.; Burghardt, T.P.

1989-01-01

The authors describe a protocol for the selective covalent labeling of the sulfhydryl 2 (SH2) on the myosin cross-bridge in glycerinated muscle fibers using the sulfhydryl-selective label 4-[N-[(iodoacetoxy)ethyl]-N-methylamino]-7-nitrobenz-2-oxa-1,3-diazole (IANBD). The protocol promotes the specificity of IANBD by using the ability to protect sulfhydryl 1 (SH1) from modification by binding the cross-bridge to the actin filament and using cross-bridge-bound MgADP to promote the accessibility of SH2. They determined the specificity of the probe using fluorescence gel scanning of fiber-extracted proteins to isolate the probe on myosin subfragment 1 (S1), limited proteolysis of the purified S1 to isolate the probe on the 20-kilodalton fragment of S1, and titration of the free SH1's on purified S1 using the radiolabeled SH1-specific reagent [ 14 C]iodoacetamide or enzymatic activity measurements. They characterized the angular distribution of the IANBD on cross-bridges in fibers when the fibers are in rigor, in relaxation, in the presence of MgADP, and in isometric contraction using wavelength-dependent fluorescence polarization. They find that the SH2 probe distinguishes the different states of the fiber such that rigor and MgADP are ordered and maintain a similar orientation throughout the excitation wavelength domain. The relaxed cross-bridge is ordered and has an orientation that is distinct from the orientation of the cross-bridge in rigor and MgADP over the entire wavelength domain. The active isometric cross-bridge is also oriented differently from the other states, suggesting the presence of a predominant actin-bound cross-bridge state that precedes the power stroke during muscle contraction

Changes in myosin S1 orientation and force induced by a temperature increase.

Science.gov (United States)

Griffiths, Peter J; Bagni, Maria A; Colombini, Barbara; Amenitsch, Heinz; Bernstorff, Sigrid; Ashley, Christopher C; Cecchi, Giovanni; Ameritsch, Heinz

2002-04-16

Force generation in myosin-based motile systems is thought to result from an angular displacement of the myosin subfragment 1 (S1) tail domain with respect to the actin filament axis. In muscle, raised temperature increases the force generated by S1, implying a greater change in tail domain angular displacement. We used time-resolved x-ray diffraction to investigate the structural corollary of this force increase by measuring M3 meridional reflection intensity during sinusoidal length oscillations. This technique allows definition of S1 orientation with respect to the myofilament axis. M3 intensity changes were approximately sinusoid at low temperatures but became increasingly distorted as temperature was elevated, with the formation of a double intensity peak at maximum shortening. This increased distortion could be accounted for by assuming a shift in orientation of the tail domain of actin-bound S1 toward the orientation at which M3 intensity is maximal, which is consistent with a tail domain rotation model of force generation in which the tail approaches a more perpendicular projection from the thin filament axis at higher temperatures. In power stroke simulations, the angle between S1 tail mean position during oscillations and the position at maximum intensity decreased by 4.7 degrees, corresponding to a mean tail displacement toward the perpendicular of 0.73 nm for a temperature-induced force increase of 0.28 P(0) from 4 to 22 degrees C. Our findings suggest that at least 62% of crossbridge compliance is associated with the tail domain.

A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects.

Science.gov (United States)

Suggs, Jennifer A; Melkani, Girish C; Glasheen, Bernadette M; Detor, Mia M; Melkani, Anju; Marsan, Nathan P; Swank, Douglas M; Bernstein, Sanford I

2017-06-01

Individuals with inclusion body myopathy type 3 (IBM3) display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K) in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in decreased in vitro

A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects

Directory of Open Access Journals (Sweden)

Jennifer A. Suggs

2017-06-01

Full Text Available Individuals with inclusion body myopathy type 3 (IBM3 display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in

Emergency disconnect means for the manipulator arm of a nuclear reactor vessel inspection apparatus

International Nuclear Information System (INIS)

Jacobs, F.; Morris, D.W.

1980-01-01

An emergency disconnect means is disclosed for uncoupling a portion of the linkage means which connects the several segments of an articulating manipulator arm employed in a nuclear reactor vessel inspection device. One of the motor housings included in the manipulator arm's segmented drive train is pivotably coupled between two segments thereof. In the event of power failure or the necessity of manual retraction of the manipulator arm from within the vessel, a lever is manually operated and moved from its normally locked position wherein the motor housing is positionally fixed to a release position wherein the motor housing and the remainder of the manipulator arm segments connected forwardly thereof are pivotally released to shorten the normal arm reach and alter the normal orientation of the manipulator arm to expedite removal without danger of collision. (auth)

[Equivalent Lever Principle of Ossicular Chain and Amplitude Reduction Effect of Internal Ear Lymph].

Science.gov (United States)

Zhao, Xiaoyan; Qin, Renjia

2015-04-01

This paper makes persuasive demonstrations on some problems about the human ear sound transmission principle in existing physiological textbooks and reference books, and puts forward the authors' view to make up for its literature. Exerting the knowledge of lever in physics and the acoustics theory, we come up with an equivalent simplified model of manubrium mallei which is to meet the requirements as the long arm of the lever. We also set up an equivalent simplified model of ossicular chain--a combination of levers of ossicular chain. We disassemble the model into two simple levers, and make full analysis and demonstration on them. Through the calculation and comparison of displacement amplitudes in both external auditory canal air and internal ear lymph, we may draw a conclusion that the key reason, which the sound displacement amplitude is to be decreased to adapt to the endurance limit of the basement membrane, is that the density and sound speed in lymph is much higher than those in the air.

Effects of lesions of the amygdala central nucleus on autoshaped lever pressing

Science.gov (United States)

Chang, Stephen E.; Wheeler, Daniel S.; Holland, Peter C.

2012-01-01

Neutral cues paired with rewards often appear to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues have been reported to modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned reinforcers in the establishment of new learning, and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped lever-pressing. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose delivery was not contingent on lever pressing, both CeA- and sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Despite their showing little evidence of impairments in autoshaped lever pressing, these same CeA-lesioned rats showed significant deficits in the expression of PIT in a subsequent phase of the experiment. The lack of impaired autoshaping in CeA-lesioned rats contrasts with effects previously reported for conditioned orienting responses (ORs) and for other putative measures of incentive learning including PIT and conditioned approach to visual cues. PMID:22386516

Estimation of distal arm joint angles from EMG and shoulder orientation for transhumeral prostheses.

Science.gov (United States)

Akhtar, Aadeel; Aghasadeghi, Navid; Hargrove, Levi; Bretl, Timothy

2017-08-01

In this paper, we quantify the extent to which shoulder orientation, upper-arm electromyography (EMG), and forearm EMG are predictors of distal arm joint angles during reaching in eight subjects without disability as well as three subjects with a unilateral transhumeral amputation and targeted reinnervation. Prior studies have shown that shoulder orientation and upper-arm EMG, taken separately, are predictors of both elbow flexion/extension and forearm pronation/supination. We show that, for eight subjects without disability, shoulder orientation and upper-arm EMG together are a significantly better predictor of both elbow flexion/extension during unilateral (R 2 =0.72) and mirrored bilateral (R 2 =0.72) reaches and of forearm pronation/supination during unilateral (R 2 =0.77) and mirrored bilateral (R 2 =0.70) reaches. We also show that adding forearm EMG further improves the prediction of forearm pronation/supination during unilateral (R 2 =0.82) and mirrored bilateral (R 2 =0.75) reaches. In principle, these results provide the basis for choosing inputs for control of transhumeral prostheses, both by subjects with targeted motor reinnervation (when forearm EMG is available) and by subjects without target motor reinnervation (when forearm EMG is not available). In particular, we confirm that shoulder orientation and upper-arm EMG together best predict elbow flexion/extension (R 2 =0.72) for three subjects with unilateral transhumeral amputations and targeted motor reinnervation. However, shoulder orientation alone best predicts forearm pronation/supination (R 2 =0.88) for these subjects, a contradictory result that merits further study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Random myosin loss along thick-filaments increases myosin attachment time and the proportion of bound myosin heads to mitigate force decline in skeletal muscle

Science.gov (United States)

Tanner, Bertrand C.W.; McNabb, Mark; Palmer, Bradley M.; Toth, Michael J.; Miller, Mark S.

2014-01-01

Diminished skeletal muscle performance with aging, disuse, and disease may be partially attributed to the loss of myofilament proteins. Several laboratories have found a disproportionate loss of myosin protein content relative to other myofilament proteins, but due to methodological limitations, the structural manifestation of this protein loss is unknown. To investigate how variations in myosin content affect ensemble cross-bridge behavior and force production we simulated muscle contraction in the half-sarcomere as myosin was removed either i) uniformly, from the Z-line end of thick-filaments, or ii) randomly, along the length of thick-filaments. Uniform myosin removal decreased force production, showing a slightly steeper force-to-myosin content relationship than the 1:1 relationship that would be expected from the loss of cross-bridges. Random myosin removal also decreased force production, but this decrease was less than observed with uniform myosin loss, largely due to increased myosin attachment time (ton) and fractional cross-bridge binding with random myosin loss. These findings support our prior observations that prolonged ton may augment force production in single fibers with randomly reduced myosin content from chronic heart failure patients. These simulation also illustrate that the pattern of myosin loss along thick-filaments influences ensemble cross-bridge behavior and maintenance of force throughout the sarcomere. PMID:24486373

Levered and unlevered Beta

OpenAIRE

Fernandez, Pablo

2003-01-01

We prove that in a world without leverage cost the relationship between the levered beta ( L) and the unlevered beta ( u) is the No-costs-of-leverage formula: L = u + ( u - d) D (1 - T) / E. We also analyze 6 alternative valuation theories proposed in the literature to estimate the relationship between the levered beta and the unlevered beta (Harris and Pringle (1985), Modigliani and Miller (1963), Damodaran (1994), Myers (1974), Miles and Ezzell (1980), and practitioners) and prove that all ...

Recognition of elementary arm movements using orientation of a tri-axial accelerometer located near the wrist

International Nuclear Information System (INIS)

Biswas, Dwaipayan; Cranny, Andy; Maharatna, Koushik; Corda, Daniele; Baldus, Giovanni; Achner, Josy; Klemke, Jasmin; Jöbges, Michael; Ortmann, Steffen

2014-01-01

In this paper we present a method for recognising three fundamental movements of the human arm (reach and retrieve, lift cup to mouth, rotation of the arm) by determining the orientation of a tri-axial accelerometer located near the wrist. Our objective is to detect the occurrence of such movements performed with the impaired arm of a stroke patient during normal daily activities as a means to assess their rehabilitation. The method relies on accurately mapping transitions of predefined, standard orientations of the accelerometer to corresponding elementary arm movements. To evaluate the technique, kinematic data was collected from four healthy subjects and four stroke patients as they performed a number of activities involved in a representative activity of daily living, ‘making-a-cup-of-tea’. Our experimental results show that the proposed method can independently recognise all three of the elementary upper limb movements investigated with accuracies in the range 91–99% for healthy subjects and 70–85% for stroke patients. (paper)

Experimental and Theoretical Investigations of a Mechanical Lever System Driven by a DC Motor

Science.gov (United States)

Nana, B.; Fautso Kuiate, G.; Yamgoué, S. B.

This paper presents theoretical and experimental results on the investigation of the dynamics of a nonlinear electromechanical system made of a lever arm actuated by a DC motor and controlled through a repulsive magnetic force. We use the method of harmonic balance to derive oscillatory solutions. Theoretical tools such as, bifurcation diagrams, Lyapunov exponents, phase portraits, are used to unveil the rich nonlinear behavior of the system including chaos and hysteresis. The experimental results are in close accordance with the theoretical predictions.

Change in hippocampal theta oscillation associated with multiple lever presses in a bimanual two-lever choice task for robot control in rats.

Directory of Open Access Journals (Sweden)

Norifumi Tanaka

Full Text Available Hippocampal theta oscillations have been implicated in working memory and attentional process, which might be useful for the brain-machine interface (BMI. To further elucidate the properties of the hippocampal theta oscillations that can be used in BMI, we investigated hippocampal theta oscillations during a two-lever choice task. During the task body-restrained rats were trained with a food reward to move an e-puck robot towards them by pressing the correct lever, ipsilateral to the robot several times, using the ipsilateral forelimb. The robot carried food and moved along a semicircle track set in front of the rat. We demonstrated that the power of hippocampal theta oscillations gradually increased during a 6-s preparatory period before the start of multiple lever pressing, irrespective of whether the correct lever choice or forelimb side were used. In addition, there was a significant difference in the theta power after the first choice, between correct and incorrect trials. During the correct trials the theta power was highest during the first lever-releasing period, whereas in the incorrect trials it occurred during the second correct lever-pressing period. We also analyzed the hippocampal theta oscillations at the termination of multiple lever pressing during the correct trials. Irrespective of whether the correct forelimb side was used, the power of hippocampal theta oscillations gradually decreased with the termination of multiple lever pressing. The frequency of theta oscillation also demonstrated an increase and decrease, before and after multiple lever pressing, respectively. There was a transient increase in frequency after the first lever press during the incorrect trials, while no such increase was observed during the correct trials. These results suggested that hippocampal theta oscillations reflect some aspects of preparatory and cognitive neural activities during the robot controlling task, which could be used for BMI.

Assisted extraction of the energy level spacings and lever arms in direct current bias measurements of one-dimensional quantum wires, using an image recognition routine

International Nuclear Information System (INIS)

Lesage, A. A. J.; Smith, L. W.; Griffiths, J. P.; Farrer, I.; Jones, G. A. C.; Ritchie, D. A.; Smith, C. G.; Al-Taie, H.; Kelly, M. J.; See, P.

2015-01-01

A multiplexer technique is used to individually measure an array of 256 split gates on a single GaAs/AlGaAs heterostructure. This results in the generation of large volumes of data, which requires the development of automated data analysis routines. An algorithm is developed to find the spacing between discrete energy levels, which form due to transverse confinement from the split gate. The lever arm, which relates split gate voltage to energy, is also found from the measured data. This reduces the time spent on the analysis. Comparison with estimates obtained visually shows that the algorithm returns reliable results for subband spacing of split gates measured at 1.4 K. The routine is also used to assess direct current bias spectroscopy measurements at lower temperatures (50 mK). This technique is versatile and can be extended to other types of measurements. For example, it is used to extract the magnetic field at which Zeeman-split 1D subbands cross one another

Stress generation by myosin minifilaments in actin bundles

International Nuclear Information System (INIS)

Dasanayake, Nilushi L; Carlsson, Anders E

2013-01-01

Forces and stresses generated by the action of myosin minifilaments are analyzed in idealized computer-generated actin bundles, and compared to results for isotropic actin networks. The bundles are generated as random collections of actin filaments in two dimensions with constrained orientations, crosslinked and attached to two fixed walls. Myosin minifilaments are placed on actin filament pairs and allowed to move and deform the network so that it exerts forces on the walls. The vast majority of simulation runs end with contractile minifilament stress, because minifilaments rotate into energetically stable contractile configurations. This process is aided by the bending and stretching of actin filaments, which accomodate minifilament rotation. Stresses for bundles are greater than those for isotropic networks, and antiparallel filaments generate more tension than parallel filaments. The forces transmitted by the actin network to the walls of the simulation cell often exceed the tension in the minifilament itself. (paper)

Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

International Nuclear Information System (INIS)

Josephson, Matthew P.; Sikkink, Laura A.; Penheiter, Alan R.; Burghardt, Thomas P.; Ajtai, Katalin

2011-01-01

Highlights: ► Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. ► Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. ► It is a widely believed that MYL2 is a poor substrate for smMLCK. ► In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. ► Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca 2+ sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis–Menten V max and K M for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant kinase in cardiac tissue on the basis of its specificity, kinetics, and tissue expression.

Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

Energy Technology Data Exchange (ETDEWEB)

Josephson, Matthew P.; Sikkink, Laura A. [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Penheiter, Alan R. [Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905 (United States); Burghardt, Thomas P., E-mail: burghardt@mayo.edu [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 (United States); Ajtai, Katalin [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States)

2011-12-16

Highlights: Black-Right-Pointing-Pointer Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. Black-Right-Pointing-Pointer Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. Black-Right-Pointing-Pointer It is a widely believed that MYL2 is a poor substrate for smMLCK. Black-Right-Pointing-Pointer In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. Black-Right-Pointing-Pointer Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca{sup 2+} sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis-Menten V{sub max} and K{sub M} for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant

Alternative S2 Hinge Regions of the Myosin Rod Affect Myofibrillar Structure and Myosin Kinetics

Energy Technology Data Exchange (ETDEWEB)

Miller, Mark S.; Dambacher, Corey M.; Knowles, Aileen F.; Braddock, Joan M.; Farman, Gerrie P.; Irving, Thomas C.; Swank, Douglas M.; Bernstein, Sanford I.; Maughan, David W.; (RPI); (IIT); (SDSU); (Vermont)

2009-07-01

The subfragment 2/light meromyosin 'hinge' region has been proposed to significantly contribute to muscle contraction force and/or speed. Transgenic replacement of the endogenous fast muscle isovariant hinge A (exon 15a) in Drosophila melanogaster indirect flight muscle with the slow muscle hinge B (exon 15b) allows examination of the structural and functional changes when only this region of the myosin molecule is different. Hinge B was previously shown to increase myosin rod length, increase A-band and sarcomere length, and decrease flight performance compared to hinge A. We applied additional measures to these transgenic lines to further evaluate the consequences of modifying this hinge region. Structurally, the longer A-band and sarcomere lengths found in the hinge B myofibrils appear to be due to the longitudinal addition of myosin heads. Functionally, hinge B, although a significant distance from the myosin catalytic domain, alters myosin kinetics in a manner consistent with this region increasing myosin rod length. These structural and functional changes combine to decrease whole fly wing-beat frequency and flight performance. Our results indicate that this hinge region plays an important role in determining myosin kinetics and in regulating thick and thin filament lengths as well as sarcomere length.

Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane

Science.gov (United States)

Kotadia, Shaila; Montembault, Emilie; Sullivan, William

2012-01-01

Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister chromatid segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in chromatid arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing chromatid arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)–depleted cells failed to elongate during segregation of long chromatids. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing chromatid arms and cortical myosin that ensures the clearance of chromatids from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity. PMID:23185030

An ARM data-oriented diagnostics package to evaluate the climate model simulation

Science.gov (United States)

Zhang, C.; Xie, S.

2016-12-01

A set of diagnostics that utilize long-term high frequency measurements from the DOE Atmospheric Radiation Measurement (ARM) program is developed for evaluating the regional simulation of clouds, radiation and precipitation in climate models. The diagnostics results are computed and visualized automatically in a python-based package that aims to serve as an easy entry point for evaluating climate simulations using the ARM data, as well as the CMIP5 multi-model simulations. Basic performance metrics are computed to measure the accuracy of mean state and variability of simulated regional climate. The evaluated physical quantities include vertical profiles of clouds, temperature, relative humidity, cloud liquid water path, total column water vapor, precipitation, sensible and latent heat fluxes, radiative fluxes, aerosol and cloud microphysical properties. Process-oriented diagnostics focusing on individual cloud and precipitation-related phenomena are developed for the evaluation and development of specific model physical parameterizations. Application of the ARM diagnostics package will be presented in the AGU session. This work is performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, IM release number is: LLNL-ABS-698645.

Portfolio Diversification with Commodity Futures: Properties of Levered Futures

NARCIS (Netherlands)

Woodard, J.D.; Egelkraut, T.M.; Garcia, P.; Pennings, J.M.E.

2005-01-01

Portfolio Diversification with Commodity Futures: Properties of Levered Futures This study extends previous work on the impact of commodity futures on portfolio performance by explicitly incorporating levered futures into the portfolio optimization problem. Using data on nine individual commodity

Azidoblebbistatin, a photoreactive myosin inhibitor

Science.gov (United States)

Képiró, Miklós; Várkuti, Boglárka H.; Bodor, Andrea; Hegyi, György; Drahos, László; Kovács, Mihály; Málnási-Csizmadia, András

2012-01-01

Photoreactive compounds are important tools in life sciences that allow precisely timed covalent crosslinking of ligands and targets. Using a unique technique we have synthesized azidoblebbistatin, which is a derivative of blebbistatin, the most widely used myosin inhibitor. Without UV irradiation azidoblebbistatin exhibits identical inhibitory properties to those of blebbistatin. Using UV irradiation, azidoblebbistatin can be covalently crosslinked to myosin, which greatly enhances its in vitro and in vivo effectiveness. Photo-crosslinking also eliminates limitations associated with the relatively low myosin affinity and water solubility of blebbistatin. The wavelength used for photo-crosslinking is not toxic for cells and tissues, which confers a great advantage in in vivo tests. Because the crosslink results in an irreversible association of the inhibitor to myosin and the irradiation eliminates the residual activity of unbound inhibitor molecules, azidoblebbistatin has a great potential to become a highly effective tool in both structural studies of actomyosin contractility and the investigation of cellular and physiological functions of myosin II. We used azidoblebbistatin to identify previously unknown low-affinity targets of the inhibitor (EC50 ≥ 50 μM) in Dictyostelium discoideum, while the strongest interactant was found to be myosin II (EC50 = 5 μM). Our results demonstrate that azidoblebbistatin, and potentially other azidated drugs, can become highly useful tools for the identification of strong- and weak-binding cellular targets and the determination of the apparent binding affinities in in vivo conditions. PMID:22647605

NRC Information Notice No. 93-22: Tripping of Klockner-Moeller molded-case circuit breakers due to support lever failure

International Nuclear Information System (INIS)

Grimes, B.K.

1993-01-01

On July 1, 1992, Virginia Electric and Power Company (VEPCO), licensee for North Anna Power Station (North Anna), Units 1 and 2, reported to the NRC that over a three-month period in 1992, three K-M model NZM6-63, 480-Vac MCCBs had tripped without appreciable load or fault condition or other electrical or mechanical transient. The three failed MCCBs were located in the cable vault and tunnel area of North Anna-2 and supplied power to motor operated valves in the charging and safety injection systems. The switch handles were found in the trip-free position and the breakers could not be relatched and reclosed. Examination of the internals of one of the three failed breakers revealed that its support lever (also described by VEPCO as a ''spring arm''), located in the rear compartment of the case, had fractured. This caused the breaker to trip and to become incapable of being reclosed. The NRC has determined that the support levers only in K-M model NZM6, NZM6b, and NZMH6 MCCBs, rated for 100 amperes and below and manufactured from 1972 on, have been made of the same type of plastic used in the support levers of the MCCBs that failed at North Anna-2

Using clinical governance levers to support change in a cancer care reform.

Science.gov (United States)

Brault, Isabelle; Denis, Jean-Louis; Sullivan, Terrence James

2015-01-01

Introducing change is a difficult issue facing all health care systems. The use of various clinical governance levers can facilitate change in health care systems. The purpose of this paper is to define clinical governance levers, and to illustrate their use in a large-scale transformation. The empirical analysis deals with the in-depth study of a specific case, which is the organizational model for Ontario's cancer sector. The authors used a qualitative research strategy and drew the data from three sources: semi-structured interviews, analysis of documents, and non-participative observations. From the results, the authors identified three phases and several steps in the reform of cancer services in this province. The authors conclude that a combination of clinical governance levers was used to transform the system. These levers operated at different levels of the system to meet the targeted objectives. To exercise clinical governance, managers need to acquire new competencies. Mobilizing clinical governance levers requires in-depth understanding of the role and scope of clinical governance levers. This study provides a better understanding of clinical governance levers. Clinical governance levers are used to implement an organizational environment that is conducive to developing clinical practice, as well as to act directly on practices to improve quality of care.

Distinct functional interactions between actin isoforms and nonsarcomeric myosins.

Directory of Open Access Journals (Sweden)

Mirco Müller

Full Text Available Despite their near sequence identity, actin isoforms cannot completely replace each other in vivo and show marked differences in their tissue-specific and subcellular localization. Little is known about isoform-specific differences in their interactions with myosin motors and other actin-binding proteins. Mammalian cytoplasmic β- and γ-actin interact with nonsarcomeric conventional myosins such as the members of the nonmuscle myosin-2 family and myosin-7A. These interactions support a wide range of cellular processes including cytokinesis, maintenance of cell polarity, cell adhesion, migration, and mechano-electrical transduction. To elucidate differences in the ability of isoactins to bind and stimulate the enzymatic activity of individual myosin isoforms, we characterized the interactions of human skeletal muscle α-actin, cytoplasmic β-actin, and cytoplasmic γ-actin with human myosin-7A and nonmuscle myosins-2A, -2B and -2C1. In the case of nonmuscle myosins-2A and -2B, the interaction with either cytoplasmic actin isoform results in 4-fold greater stimulation of myosin ATPase activity than was observed in the presence of α-skeletal muscle actin. Nonmuscle myosin-2C1 is most potently activated by β-actin and myosin-7A by γ-actin. Our results indicate that β- and γ-actin isoforms contribute to the modulation of nonmuscle myosin-2 and myosin-7A activity and thereby to the spatial and temporal regulation of cytoskeletal dynamics. FRET-based analyses show efficient copolymerization abilities for the actin isoforms in vitro. Experiments with hybrid actin filaments show that the extent of actomyosin coupling efficiency can be regulated by the isoform composition of actin filaments.

Single molecule fluorescence image patterns linked to dipole orientation and axial position: application to myosin cross-bridges in muscle fibers.

Directory of Open Access Journals (Sweden)

Thomas P Burghardt

2011-02-01

Full Text Available Photoactivatable fluorescent probes developed specifically for single molecule detection extend advantages of single molecule imaging to high probe density regions of cells and tissues. They perform in the native biomolecule environment and have been used to detect both probe position and orientation.Fluorescence emission from a single photoactivated probe captured in an oil immersion, high numerical aperture objective, produces a spatial pattern on the detector that is a linear combination of 6 independent and distinct spatial basis patterns with weighting coefficients specifying emission dipole orientation. Basis patterns are tabulated for single photoactivated probes labeling myosin cross-bridges in a permeabilized muscle fiber undergoing total internal reflection illumination. Emitter proximity to the glass/aqueous interface at the coverslip implies the dipole near-field and dipole power normalization are significant affecters of the basis patterns. Other characteristics of the basis patterns are contributed by field polarization rotation with transmission through the microscope optics and refraction by the filter set. Pattern recognition utilized the generalized linear model, maximum likelihood fitting, for Poisson distributed uncertainties. This fitting method is more appropriate for treating low signal level photon counting data than χ(2 minimization.Results indicate that emission dipole orientation is measurable from the intensity image except for the ambiguity under dipole inversion. The advantage over an alternative method comparing two measured polarized emission intensities using an analyzing polarizer is that information in the intensity spatial distribution provides more constraints on fitted parameters and a single image provides all the information needed. Axial distance dependence in the emission pattern is also exploited to measure relative probe position near focus. Single molecule images from axial scanning fitted

Robust mechanobiological behavior emerges in heterogeneous myosin systems

Science.gov (United States)

Egan, Paul F.; Moore, Jeffrey R.; Ehrlicher, Allen J.; Weitz, David A.; Schunn, Christian; Cagan, Jonathan; LeDuc, Philip

2017-09-01

Biological complexity presents challenges for understanding natural phenomenon and engineering new technologies, particularly in systems with molecular heterogeneity. Such complexity is present in myosin motor protein systems, and computational modeling is essential for determining how collective myosin interactions produce emergent system behavior. We develop a computational approach for altering myosin isoform parameters and their collective organization, and support predictions with in vitro experiments of motility assays with α-actinins as molecular force sensors. The computational approach models variations in single myosin molecular structure, system organization, and force stimuli to predict system behavior for filament velocity, energy consumption, and robustness. Robustness is the range of forces where a filament is expected to have continuous velocity and depends on used myosin system energy. Myosin systems are shown to have highly nonlinear behavior across force conditions that may be exploited at a systems level by combining slow and fast myosin isoforms heterogeneously. Results suggest some heterogeneous systems have lower energy use near stall conditions and greater energy consumption when unloaded, therefore promoting robustness. These heterogeneous system capabilities are unique in comparison with homogenous systems and potentially advantageous for high performance bionanotechnologies. Findings open doors at the intersections of mechanics and biology, particularly for understanding and treating myosin-related diseases and developing approaches for motor molecule-based technologies.

Myosin Light Chain Kinase and the Role of Myosin Light Chain Phosphorylation in Skeletal Muscle

Science.gov (United States)

Stull, James T.; Kamm, Kristine E.; Vandenboom, Rene

2011-01-01

Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca2+/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca2+ binding to calmodulin forming a (Ca2+)4•calmodulin complex sufficient for activation with a diffusion limited, stoichiometic binding and displacement of a regulatory segment from skMLCK catalytic core. The N-terminal sequence of RLC then extends through the exposed catalytic cleft for Ser15 phosphorylation. Removal of Ca2+ results in the slow dissociation of calmodulin and inactivation of skMLCK. Combined biochemical properties provide unique features for the physiological responsiveness of RLC phosphorylation, including (1) rapid activation of MLCK by Ca2+/calmodulin, (2) limiting kinase activity so phosphorylation is slower than contraction, (3) slow MLCK inactivation after relaxation and (4) much greater kinase activity relative to myosin light chain phosphatase (MLCP). SkMLCK phosphorylation of myosin RLC modulates mechanical aspects of vertebrate skeletal muscle function. In permeabilized skeletal muscle fibers, phosphorylation-mediated alterations in myosin structure increase the rate of force-generation by myosin cross bridges to increase Ca2+-sensitivity of the contractile apparatus. Stimulation-induced increases in RLC phosphorylation in intact muscle produces isometric and concentric force potentiation to enhance dynamic aspects of muscle work and power in unfatigued or fatigued muscle. Moreover, RLC phosphorylation-mediated enhancements may interact with neural strategies for human skeletal muscle activation to ameliorate either central or peripheral aspects of fatigue. PMID:21284933

A global, myosin light chain kinase-dependent increase in myosin II contractility accompanies the metaphase-anaphase transition in sea urchin eggs.

Science.gov (United States)

Lucero, Amy; Stack, Christianna; Bresnick, Anne R; Shuster, Charles B

2006-09-01

Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase-anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase-anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus.

A Global, Myosin Light Chain Kinase-dependent Increase in Myosin II Contractility Accompanies the Metaphase–Anaphase Transition in Sea Urchin Eggs

Science.gov (United States)

Lucero, Amy; Stack, Christianna; Bresnick, Anne R.

2006-01-01

Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase–anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase–anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus. PMID:16837551

Levers Histopathology of the Skin* .,

African Journals Online (AJOL)

Books. Levers Histopathology of the Skin*. By David Elder, Rosalie Elenitsas, Christine Jaworsky and. Bernett Johnson ... for the poor quality of most of the black and white clinical pictures, which ... R85. Long. Me~ord, UK: E B Adams, 1996.

Fabrication of tungsten tip for scanning tunneling microscope by the lever principle

International Nuclear Information System (INIS)

Wang Yang; Wang Huabin; Chinese Academy of Sciences, Beijing; Gong Jinlong; Zhu Dezhang

2007-01-01

A novel experimental setup was designed to fabricate tungsten tips for scanning tunneling microscope (STM), based on simple mechanical lever principle. The equipment can quickly separate the tip from electrolyte to avoid the further etching of the fine-shaped tungsten tip. The setup is advantageous for its simplicity over complex electronic control systems. The use result in scanning electron microscope demonstrates that the radius of the tip can reach 50 nm. The tip was applied to scan the surface of highly-oriented pyrolytic graphite, and the results were satisfactory. It is shown that the tip can be used for the scanning of atomically resolved images. (authors)

Noninvasive determination of optical lever sensitivity in atomic force microscopy

International Nuclear Information System (INIS)

Higgins, M.J.; Proksch, R.; Sader, J.E.; Polcik, M.; Mc Endoo, S.; Cleveland, J.P.; Jarvis, S.P.

2006-01-01

Atomic force microscopes typically require knowledge of the cantilever spring constant and optical lever sensitivity in order to accurately determine the force from the cantilever deflection. In this study, we investigate a technique to calibrate the optical lever sensitivity of rectangular cantilevers that does not require contact to be made with a surface. This noncontact approach utilizes the method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] to calibrate the spring constant of the cantilever in combination with the equipartition theorem [J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993)] to determine the optical lever sensitivity. A comparison is presented between sensitivity values obtained from conventional static mode force curves and those derived using this noncontact approach for a range of different cantilevers in air and liquid. These measurements indicate that the method offers a quick, alternative approach for the calibration of the optical lever sensitivity

Noninvasive determination of optical lever sensitivity in atomic force microscopy

Science.gov (United States)

Higgins, M. J.; Proksch, R.; Sader, J. E.; Polcik, M.; Mc Endoo, S.; Cleveland, J. P.; Jarvis, S. P.

2006-01-01

Atomic force microscopes typically require knowledge of the cantilever spring constant and optical lever sensitivity in order to accurately determine the force from the cantilever deflection. In this study, we investigate a technique to calibrate the optical lever sensitivity of rectangular cantilevers that does not require contact to be made with a surface. This noncontact approach utilizes the method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] to calibrate the spring constant of the cantilever in combination with the equipartition theorem [J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993)] to determine the optical lever sensitivity. A comparison is presented between sensitivity values obtained from conventional static mode force curves and those derived using this noncontact approach for a range of different cantilevers in air and liquid. These measurements indicate that the method offers a quick, alternative approach for the calibration of the optical lever sensitivity.

Direct observation of the myosin Va recovery stroke that contributes to unidirectional stepping along actin.

Directory of Open Access Journals (Sweden)

Katsuyuki Shiroguchi

2011-04-01

Full Text Available Myosins are ATP-driven linear molecular motors that work as cellular force generators, transporters, and force sensors. These functions are driven by large-scale nucleotide-dependent conformational changes, termed "strokes"; the "power stroke" is the force-generating swinging of the myosin light chain-binding "neck" domain relative to the motor domain "head" while bound to actin; the "recovery stroke" is the necessary initial motion that primes, or "cocks," myosin while detached from actin. Myosin Va is a processive dimer that steps unidirectionally along actin following a "hand over hand" mechanism in which the trailing head detaches and steps forward ∼72 nm. Despite large rotational Brownian motion of the detached head about a free joint adjoining the two necks, unidirectional stepping is achieved, in part by the power stroke of the attached head that moves the joint forward. However, the power stroke alone cannot fully account for preferential forward site binding since the orientation and angle stability of the detached head, which is determined by the properties of the recovery stroke, dictate actin binding site accessibility. Here, we directly observe the recovery stroke dynamics and fluctuations of myosin Va using a novel, transient caged ATP-controlling system that maintains constant ATP levels through stepwise UV-pulse sequences of varying intensity. We immobilized the neck of monomeric myosin Va on a surface and observed real time motions of bead(s attached site-specifically to the head. ATP induces a transient swing of the neck to the post-recovery stroke conformation, where it remains for ∼40 s, until ATP hydrolysis products are released. Angle distributions indicate that the post-recovery stroke conformation is stabilized by ≥ 5 k(BT of energy. The high kinetic and energetic stability of the post-recovery stroke conformation favors preferential binding of the detached head to a forward site 72 nm away. Thus, the recovery

The musculature of coleoid cephalopod arms and tentacles

Directory of Open Access Journals (Sweden)

William McKee Kier

2016-02-01

Full Text Available The regeneration of coleoid cephalopod arms and tentacles is a common occurrence, recognized since Aristotle. The complexity of the arrangement of the muscle and connective tissues of these appendages make them of great interest for research on regeneration. They lack rigid skeletal elements and consist of a three-dimensional array of muscle fibers, relying on a type of skeletal support system called a muscular hydrostat. Support and movement in the arms and tentacles depends on the fact that muscle tissue resists volume change. The basic principle of function is straightforward; because the volume of the appendage is essentially constant, a decrease in one dimension must result in an increase in another dimension. Since the muscle fibers are arranged in three mutually perpendicular directions, all three dimensions can be actively controlled and thus a remarkable diversity of movements and deformations can be produced. In the arms and tentacles of coleoids, three main muscle orientations are observed: 1 transverse muscle fibers arranged in planes perpendicular to the longitudinal axis; 2 longitudinal muscle fibers typically arranged in bundles parallel to the longitudinal axis; and 3 helical or obliquely arranged layers of muscle fibers, arranged in both right- and left-handed helixes. By selective activation of these muscle groups, elongation, shortening, bending, torsion and stiffening of the appendage can be produced. The predominant muscle fiber type is obliquely striated. Cross-striated fibers are found only in the transverse muscle mass of the prey capture tentacles of squid and cuttlefish. These fibers have unusually short myofilaments and sarcomeres, generating the high shortening velocity required for rapid elongation of the tentacles. It is likely that coleoid cephalopods use ultrastructural modifications rather than tissue-specific myosin isoforms to tune contraction velocities.

CHARACTERIZATION OF TIGHTLY-ASSOCIATED SMOOTH MUSCLE MYOSIN-MYOSIN LIGHT CHAIN KINASE-CALMODULIN COMPLEXES*

OpenAIRE

Hong, Feng; Haldeman, Brian D.; John, Olivia A.; Brewer, Paul D.; Wu, Yi-Ying; Ni, Shaowei; Wilson, David P.; Walsh, Michael P.; Baker, Jonathan E.; Cremo, Christine R.

2009-01-01

A current popular model to explain phosphorylation of smooth muscle myosin (SMM) by smooth muscle myosin light chain kinase (MLCK) proposes that MLCK is bound tightly to actin but weakly to SMM. We found that MLCK and calmodulin (CaM) co-purify with unphosphorylated SMM (up-SMM) from chicken gizzard, suggesting that they are tightly bound. Although the MLCK:SMM molar ratio in SMM preparations was well below stoichiometric (1:73 ± 9), the ratio was ~ 23–37% of that in gizzard tissue. Fifteen t...

Preparation of human cardiac anti-myosin: a review

International Nuclear Information System (INIS)

Okada, H.; Souza, I.T.T.

1990-01-01

The present communication is a review of the physicochemical characterization and immunological properties of myosin isolated from the cardiac muscle, the production of monoclonal antibody anti-myosin, the radiolabeling of this antibody and its applications as radiopharmaceuticals to imaging myocardial infarcts. The classical example of radioimmunologic diagnosis of non malignant tissues is the detection of myocardial infarction by radiolabeled antibodies to myosin. (author)

Does the Lever Sign Test Have Added Value for Diagnosing Anterior Cruciate Ligament Ruptures?

Science.gov (United States)

Lichtenberg, Miranda C.; Koster, Christiaan H.; Teunissen, Lennart P.J.; Oosterveld, Frits G.J.; Harmsen, Annelieke M.K.; Haverkamp, Daniel; Hoornenborg, Daniel; Berg, Robert P.; Bloemers, Frank W.; Faber, Irene R.

2018-01-01

Background: Diagnosing an anterior cruciate ligament (ACL) rupture based on a physical examination remains a challenge for both surgeons and physical therapists. The lever sign test was developed to overcome the practical limitations of other tests and to optimize diagnosis. An evaluation of the measurement properties of the lever sign test is needed to make adequate interpretations in practice. Purpose: To evaluate the reliability and diagnostic value of the lever sign test. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 94 patients were recruited between November 2014 and July 2016. Patients were included if they were at least 16 years old, suffered from knee trauma, and had indications for knee arthroscopic surgery. Lever sign, anterior drawer, Lachman, and pivot-shift test outcomes were examined by an orthopaedic/trauma surgeon and a physical therapist. A test-retest design was used to investigate interrater reliability. Moreover, the lever sign test outcomes, alone and in combination with the other diagnostic tests, were compared with arthroscopic results, which served as the gold standard for the test’s diagnostic value. Results: The lever sign test and pivot-shift test had kappa values exceeding 0.80 for interrater reliability. The kappa values for the anterior drawer test and Lachman test were 0.80 and 0.77, respectively. The lever sign test showed the highest specificity (100%) and the lowest sensitivity (39%) when compared with the other 3 tests. Moreover, its positive and negative predictive values were 100% and 65%, respectively, while an accuracy of 71% was calculated. Clustering the lever sign test parallel with the other 3 tests resulted in the highest accuracy of 91%. Conclusion: The lever sign test appears to have high interrater reliability and is the most specific test, showing a maximal positive predictive value. A positive lever sign test result indicates an ACL rupture. These results support the added value

Ergonomic Evaluation of Space Shuttle Light-Weight Seat Lever Position and Operation

Science.gov (United States)

Maida, J.; Rajulu, Sudhakar L.; Bond, Robert L. (Technical Monitor)

2000-01-01

During a Shuttle flight in the early part of 1999, one of the crewmembers was unable to operate the backrest lever for the light-weight seat in microgravity. It is essential that the crewmembers are able to adjust this back-rest lever, which is titled forward 2 degrees from vertical during launch and then moved backwards to 10 degrees aft of vertical upon reaching orbit. This adjustment is needed to cushion the crewmembers during an inadvertent crash landing situation. The original Shuttle seats, which had seat controls located on the front left and right sides of the seat, were replaced recently with the new light-weight seats. The controls for these new, seats were moved to the night side with one control at the front and the other at the back. While it was uncertain whether the problem encountered was unique to that crewmember or not it was clear to the personnel responsible for maintaining the Shuttle seats that not knowing the cause of the problem posed a safety concern for NASA. Hence the Anthropometry and Biomechanics Facility (ABF) of the Johnson Space Center was requested to perform an evaluation of the seat controls and provide NASA with appropriate recommendations on whether the seat lever positions and operations should be modified. The ABF designed an experiment to investigate the amount of pull force exerted by subjects, wearing an unpressurized or pressurized crew launch escape suit, when controls were placed in the front and back (on the right side) of the light-weight seat. Single-axis load cells were attached to the seat levers, which measured the maximum static pull forces that were exerted by the subjects. Twelve subjects, six male and six female, participated in this study. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results from this study showed that as a whole (or in general), the subjects were able to pull on the lever at the back position with

Myosin II dynamics are regulated by tension in intercalating cells.

Science.gov (United States)

Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

2009-11-01

Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

Myosin Light Chain Kinase and the Role of Myosin Light Chain Phosphorylation in Skeletal Muscle

OpenAIRE

Stull, James T.; Kamm, Kristine E.; Vandenboom, Rene

2011-01-01

Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca2+/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca2+ binding to calmodulin forming a (Ca2+)4•calmodulin complex sufficient for activation with a diffusion limited, stoichiometic bindin...

Characterization of myosin light chain in shrimp hemocytic phagocytosis.

Science.gov (United States)

Han, Fang; Wang, Zhiyong; Wang, Xiaoqing

2010-11-01

Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes that are involved in material transport, muscle shrink and cell division. However, its function in phagocytosis against invading pathogens in crustacean remains unknown. In this investigation, a myosin light chain gene was obtained from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766 bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino acids. The myosin light chain protein was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified GST fusion protein. As revealed by immuno-electron microscopy, the myosin light chain protein was only expressed in the dark bands of muscle. In the present study, the myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed by real-time PCR and western blot. And the phagocytic percentage and phagocytic index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the WSSV-resistant shrimp, suggesting that the myosin light chain protein was essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated that the phagocytic percentage and phagocytic index were significantly decreased when the myosin light chain gene was silenced by sequence-specific siRNA. These findings suggested that myosin light chain protein was involved in the regulation of hemocytic phagocytosis of shrimp. Copyright 2010 Elsevier Ltd. All rights reserved.

Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain.

Science.gov (United States)

Wollscheid, Hans-Peter; Biancospino, Matteo; He, Fahu; Magistrati, Elisa; Molteni, Erika; Lupia, Michela; Soffientini, Paolo; Rottner, Klemens; Cavallaro, Ugo; Pozzoli, Uberto; Mapelli, Marina; Walters, Kylie J; Polo, Simona

2016-04-01

Myosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VI(short) and myosin VI(long), which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the α2-linker structurally defines a new clathrin-binding domain that is unique to myosin VI(long) and masks the known RRL interaction motif. This finding is relevant to ovarian cancer, in which alternative myosin VI splicing is aberrantly regulated, and exon skipping dictates cell addiction to myosin VI(short) in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VI(short). Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles.

An analysis of policy levers used to implement mental health reform in Australia 1992-2012.

Science.gov (United States)

Grace, Francesca C; Meurk, Carla S; Head, Brian W; Hall, Wayne D; Carstensen, Georgia; Harris, Meredith G; Whiteford, Harvey A

2015-10-24

Over the past two decades, mental health reform in Australia has received unprecedented government attention. This study explored how five policy levers (organisation, regulation, community education, finance and payment) were used by the Australian Federal Government to implement mental health reforms. Australian Government publications, including the four mental health plans (published in 1992, 1998, 2003 and 2008) were analysed according to policy levers used to drive reform across five priority areas: [1] human rights and community attitudes; [2] responding to community need; [3] service structures; [4] service quality and effectiveness; and [5] resources and service access. Policy levers were applied in varying ways; with two or three levers often concurrently used to implement a single initiative or strategy. For example, changes to service structures were achieved using various combinations of all five levers. Attempts to improve service quality and effectiveness were instead made through a single lever-regulation. The use of some levers changed over time, including a move away from prescriptive, legislative use of regulation, towards a greater focus on monitoring service standards and consumer outcomes. Patterns in the application of policy levers across the National Mental Health Strategy, as identified in this analysis, represent a novel way of conceptualising the history of mental health reform in Australia. An improved understanding of the strategic targeting and appropriate utilisation of policy levers may assist in the delivery and evaluation of evidence-based mental health reform in the future.

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

Science.gov (United States)

Betapudi, Venkaiah

2014-07-01

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

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

Directory of Open Access Journals (Sweden)

Venkaiah eBetapudi

2014-07-01

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

Topology of interaction between titin and myosin thick filaments.

Science.gov (United States)

Kellermayer, Miklós; Sziklai, Dominik; Papp, Zsombor; Decker, Brennan; Lakatos, Eszter; Mártonfalvi, Zsolt

2018-05-05

Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the A-band titin is associated with the myosin thick filament. It has been speculated that titin may serve as a blueprint for thick-filament formation due to the super-repeat structure of its A-band domains. Accordingly, titin might provide a template that determines the length and structural periodicity of the thick filament. Here we tested the titin ruler hypothesis by mixing titin and myosin at in situ stoichiometric ratios (300 myosins per 12 titins) in buffers of different ionic strength (KCl concentration range 100-300 mM). The topology of the filamentous complexes was investigated with atomic force microscopy. We found that the samples contained distinct, segregated populations of titin molecules and myosin thick filaments. We were unable to identify complexes in which myosin molecules were regularly associated to either mono- or oligomeric titin in either relaxed or stretched states of the titin filaments. Thus, the electrostatically driven self-association is stronger in both myosin and titin than their binding to each other, and it is unlikely that titin functions as a geometrical template for thick-filament formation. However, when allowed to equilibrate configurationally, long myosin thick filaments appeared with titin oligomers attached to their surface. The titin meshwork formed on the thick-filament surface may play a role in controlling thick-filament length by regulating the structural dynamics of myosin molecules and placing a mechanical limit on the filament length. Copyright © 2018 Elsevier Inc. All rights reserved.

ARM Data-Oriented Metrics and Diagnostics Package for Climate Model Evaluation Value-Added Product

Energy Technology Data Exchange (ETDEWEB)

Zhang, Chengzhu [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Xie, Shaocheng [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-10-15

A Python-based metrics and diagnostics package is currently being developed by the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Infrastructure Team at Lawrence Livermore National Laboratory (LLNL) to facilitate the use of long-term, high-frequency measurements from the ARM Facility in evaluating the regional climate simulation of clouds, radiation, and precipitation. This metrics and diagnostics package computes climatological means of targeted climate model simulation and generates tables and plots for comparing the model simulation with ARM observational data. The Coupled Model Intercomparison Project (CMIP) model data sets are also included in the package to enable model intercomparison as demonstrated in Zhang et al. (2017). The mean of the CMIP model can serve as a reference for individual models. Basic performance metrics are computed to measure the accuracy of mean state and variability of climate models. The evaluated physical quantities include cloud fraction, temperature, relative humidity, cloud liquid water path, total column water vapor, precipitation, sensible and latent heat fluxes, and radiative fluxes, with plan to extend to more fields, such as aerosol and microphysics properties. Process-oriented diagnostics focusing on individual cloud- and precipitation-related phenomena are also being developed for the evaluation and development of specific model physical parameterizations. The version 1.0 package is designed based on data collected at ARM’s Southern Great Plains (SGP) Research Facility, with the plan to extend to other ARM sites. The metrics and diagnostics package is currently built upon standard Python libraries and additional Python packages developed by DOE (such as CDMS and CDAT). The ARM metrics and diagnostic package is available publicly with the hope that it can serve as an easy entry point for climate modelers to compare their models with ARM data. In this report, we first present the input data, which

Effects of proteolysis on the adenosinetriphosphatase activities of thymus myosin

International Nuclear Information System (INIS)

Vu, N.D.; Wagner, P.D.

1987-01-01

Limited proteolysis was used to identify regions on the heavy chains of calf thymus myosin which may be involved in ATP and actin binding. Assignments of the various proteolytic fragments to different parts of the myosin heavy chain were based on solubility, gel filtration, electron microscopy, and binding of 32 P-labeled regulatory light chains. Chymotrypsin rapidly cleaved within the head of thymus myosin to give a 70,000-dalton N-terminal fragment and a 140,000-dalton C-terminal fragment. These two fragments did not dissociate under nondenaturing conditions. Cleavage within the myosin tail to give heavy meromyosin occurred more slowly. Cleavage at the site 70,000 daltons from the N-terminus of the heavy chain caused about a 30-fold decrease in the actin concentration required to achieve half-maximal stimulation of the magnesium-adenosinetriphosphatase (Mg-ATPase) activity of unphosphorylated thymus myosin. The actin-activated ATPase activity of this digested myosin was only slightly affected by light chain phosphorylation. Actin inhibited the cleavage at this site by chymotrypsin. In the presence of ATP, chymotrypsin rapidly cleaved the thymus myosin heavy chain at an additional site about 4000 daltons from the N-terminus. Cleavage at this site caused a 2-fold increase in the ethylenediaminetetraacetic acid-ATPase activity and 3-fold decreases in the Ca 2+ - and Mg-ATPase activities of thymus myosin. Thus, cleavage at the N-terminus of thymus myosin was affected by ATP, and this cleavage altered ATPase activity. Papain cleaved the thymus myosin heavy chain about 94,000 daltons from the N-terminus to give subfragment 1. Although this subfragment 1 contained intact light chains, its actin-activated ATPase activity was not affected by light chain phosphorylation

Functions of myosin motors tailored for parasitism

DEFF Research Database (Denmark)

Mueller, Christina; Graindorge, Arnault; Soldati-Favre, Dominique

2017-01-01

Myosin motors are one of the largest protein families in eukaryotes that exhibit divergent cellular functions. Their roles in protozoans, a diverse group of anciently diverged, single celled organisms with many prominent members known to be parasitic and to cause diseases in human and livestock......, are largely unknown. In the recent years many different approaches, among them whole genome sequencing, phylogenetic analyses and functional studies have increased our understanding on the distribution, protein architecture and function of unconventional myosin motors in protozoan parasites. In Apicomplexa......, myosins turn out to be highly specialized and to exhibit unique functions tailored to accommodate the lifestyle of these parasites....

La Lever house, New York

Directory of Open Access Journals (Sweden)

Sergio de Miguel

2012-12-01

Full Text Available

Resumen

En el último siglo la mítica ciudad de Nueva York ha sido capaz de definir y transmitir las más contagiosas propuestas de  construcción del futuro.
El edificio de la Lever House, erigido en el corazón de Manhattan al comienzo de la prodigiosa década de los cincuenta, consiguió ser la constatación de que el perseguido sueño de la “torre de cristal” era por fin posible. La poética y secular conquista de la  levedad avanzó entonces a través de un prosaico y paradójico objeto publicitario. Un particular crisol de negocio, oportunidad y audacia hicieron de ésta sorprendente pieza un icono   fundamental de la globalizada arquitectura moderna americana.

Nota* En la edición electrónica este artículo se ha publicado con toda documentación gráfica aportada por el autor.

Palabras clave

Lever house, torre, levedad, cristal, publicidad, icono

Abstract

In the last century, the mythical city of New York has been able to define and transmit the most contagious proposals of  innovative construction.
The Lever House Building, erected in the heart of Manhattan at  the start of the prodigious 1950s managed to become a  statement for the possibility of finally realizing the sought‐after
dream of building a glass tower. The poetics and secular   conquest of lightness therefore made a leap forward through a prosaic and paradoxical publicity item. A special crucible of business, opportunity and audacity made a fundamental icon of globalized modern American Architecture out of this surprising work.

Note * In the online edition this article is published with all graphic material provided by the author.

Reciprocal and dynamic polarization of planar cell polarity core components and myosin

Science.gov (United States)

Newman-Smith, Erin; Kourakis, Matthew J; Reeves, Wendy; Veeman, Michael; Smith, William C

2015-01-01

The Ciona notochord displays planar cell polarity (PCP), with anterior localization of Prickle (Pk) and Strabismus (Stbm). We report that a myosin is polarized anteriorly in these cells and strongly colocalizes with Stbm. Disruption of the actin/myosin machinery with cytochalasin or blebbistatin disrupts polarization of Pk and Stbm, but not of myosin complexes, suggesting a PCP-independent aspect of myosin localization. Wash out of cytochalasin restored Pk polarization, but not if done in the presence of blebbistatin, suggesting an active role for myosin in core PCP protein localization. On the other hand, in the pk mutant line, aimless, myosin polarization is disrupted in approximately one third of the cells, indicating a reciprocal action of core PCP signaling on myosin localization. Our results indicate a complex relationship between the actomyosin cytoskeleton and core PCP components in which myosin is not simply a downstream target of PCP signaling, but also required for PCP protein localization. DOI: http://dx.doi.org/10.7554/eLife.05361.001 PMID:25866928

Evolutionary traces decode molecular mechanism behind fast pace of myosin XI

Directory of Open Access Journals (Sweden)

Syamaladevi Divya P

2011-09-01

Full Text Available Abstract Background Cytoplasmic class XI myosins are the fastest processive motors known. This class functions in high-velocity cytoplasmic streaming in various plant cells from algae to angiosperms. The velocities at which they process are ten times faster than its closest class V homologues. Results To provide sequence determinants and structural rationale for the molecular mechanism of this fast pace myosin, we have compared the sequences from myosin class V and XI through Evolutionary Trace (ET analysis. The current study identifies class-specific residues of myosin XI spread over the actin binding site, ATP binding site and light chain binding neck region. Sequences for ET analysis were accumulated from six plant genomes, using literature based text search and sequence searches, followed by triple validation viz. CDD search, string-based searches and phylogenetic clustering. We have identified nine myosin XI genes in sorghum and seven in grape by sequence searches. Both the plants possess one gene product each belonging to myosin type VIII as well. During this process, we have re-defined the gene boundaries for three sorghum myosin XI genes using fgenesh program. Conclusion Molecular modelling and subsequent analysis of putative interactions involving these class-specific residues suggest a structural basis for the molecular mechanism behind high velocity of plant myosin XI. We propose a model of a more flexible switch I region that contributes to faster ADP release leading to high velocity movement of the algal myosin XI.

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus

Czech Academy of Sciences Publication Activity Database

Venit, Tomáš; Dzijak, Rastislav; Kalendová, Alžběta; Kahle, Michal; Rohožková, Jana; Schmidt, V.; Rülicke, T.; Rathkolb, B.; Hans, W.; Bohla, A.; Eickelberg, O.; Stoeger, T.; Wolf, E.; Yildirim, A.Ö.; Gailus-Durner, V.; Fuchs, H.; de Angelis, M.H.; Hozák, Pavel

2013-01-01

Roč. 8, č. 4 (2013), e61406 E-ISSN 1932-6203 R&D Projects: GA ČR GAP305/11/2232; GA TA ČR TE01020022; GA MŠk LH12143; GA ČR(CZ) GD204/09/H084 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : nuclear myosin * myosin isoforms * cell nucleus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013

Mechanical efficiency of two commercial lever-propulsion mechanisms for manual wheelchair locomotion.

Science.gov (United States)

Lui, Jordon; MacGillivray, Megan K; Sheel, A William; Jeyasurya, Jeswin; Sadeghi, Mahsa; Sawatzky, Bonita Jean

2013-01-01

The purpose of this study was to (1) evaluate the mechanical efficiency (ME) of two commercially available lever-propulsion mechanisms for wheelchairs and (2) compare the ME of lever propulsion with hand rim propulsion within the same wheelchair. Of the two mechanisms, one contained a torsion spring while the other used a roller clutch design. We hypothesized that the torsion spring mechanism would increase the ME of propulsion due to a passive recovery stroke enabled by the mechanism. Ten nondisabled male participants with no prior manual wheeling experience performed submaximal exercise tests using both lever-propulsion mechanisms and hand rim propulsion on two different wheelchairs. Cardiopulmonary parameters including oxygen uptake (VO2), heart rate (HR), and energy expenditure (En) were determined. Total external power (Pext) was measured using a drag test protocol. ME was determined by the ratio of Pext to En. Results indicated no significant effect of lever-propulsion mechanism for all physiological measures tested. This suggests that the torsion spring did not result in a physiological benefit compared with the roller clutch mechanism. However, both lever-propulsion mechanisms showed decreased VO2 and HR and increased ME (as a function of slope) compared with hand rim propulsion (p propulsion mechanisms tested are more mechanically efficient than conventional hand rim propulsion, especially when slopes are encountered.

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Science.gov (United States)

2010-10-01

... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical interlocking machine, locking between electric and mechanical levers shall be maintained so that mechanical... 49 Transportation 4 2010-10-01 2010-10-01 false Electromechanical interlocking machine; locking...

Actin and myosin contribute to mammalian mitochondrial DNA maintenance

Science.gov (United States)

Reyes, A.; He, J.; Mao, C. C.; Bailey, L. J.; Di Re, M.; Sembongi, H.; Kazak, L.; Dzionek, K.; Holmes, J. B.; Cluett, T. J.; Harbour, M. E.; Fearnley, I. M.; Crouch, R. J.; Conti, M. A.; Adelstein, R. S.; Walker, J. E.; Holt, I. J.

2011-01-01

Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and β-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of β-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some β-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance. PMID:21398640

Phosphorylation of human skeletal muscle myosin

International Nuclear Information System (INIS)

Houston, M.E.; Lingley, M.D.; Stuart, D.S.; Hoffman-Goetz, L.

1986-01-01

Phosphorylation of the P-light chains (phosphorylatable light chains) in human skeletal muscle myosin was studied in vitro and in vivo under resting an d contracted conditions. biopsy samples from rested vastus lateralis muscle of male and female subjects were incubated in oxygenated physiological solution at 30 0 C. Samples frozen following a quiescent period showed the presence of only unphosphorylated P-light chains designated LC2f (light chain two of fast myosin) CL2s and LC2s'(light chains two of slow myosin). Treatment with caffeine (10 mM) or direct electrical stimulation resulted in the appearance of three additional bands which were identified as the phosphorylated forms of the P-light chains i.e. LC2f-P, LC2s-P and LC2s'-P. The presence of phosphate was confirmed by prior incubation with ( 30 P) orthophosphate. Muscle samples rapidly frozen from resting vastus lateralis muscle revealed the presence of unphosphorylated and phosphorylated P-light chains in approximately equal ratios. Muscle samples rapidly frozen following a maximal 10 second isometric contraction showed virtually only phosphorylated fast and slow P-light chains. These results reveal that the P-light chains in human fast and slow myosin may be rapidly phosphorylated, but the basal level of phosphorylation in rested human muscle considerably exceeds that observed in animal muscles studied in vitro or in situ

Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

Science.gov (United States)

Platz, T; Eickhof, C; van Kaick, S; Engel, U; Pinkowski, C; Kalok, S; Pause, M

2005-10-01

To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Single blind, multicentre randomized control trial. Three inpatient neurorehabilitation centres. Sixty-two anterior circulation ischaemic stroke patients. Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

Myosin heavy chain expression in rabbit masseter muscle during postnatal development

NARCIS (Netherlands)

Bredman, J. J.; Weijs, W. A.; Korfage, H. A.; Brugman, P.; Moorman, A. F.

1992-01-01

The expression of isoforms of myosin heavy chain (MHC) during postnatal development was studied in the masseter muscle of the rabbit. Evidence is presented that in addition to adult fast and slow myosin, the rabbit masseter contains neonatal and 'cardiac' alpha-MHC. During postnatal growth myosin

Identification of signals that facilitate isoform specific nucleolar localization of myosin IC

Energy Technology Data Exchange (ETDEWEB)

Schwab, Ryan S.; Ihnatovych, Ivanna; Yunus, Sharifah Z.S.A.; Domaradzki, Tera [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States); Hofmann, Wilma A., E-mail: whofmann@buffalo.edu [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States)

2013-05-01

Myosin IC is a single headed member of the myosin superfamily that localizes to the cytoplasm and the nucleus, where it is involved in transcription by RNA polymerases I and II, intranuclear transport, and nuclear export. In mammalian cells, three isoforms of myosin IC are expressed that differ only in the addition of short isoform-specific N-terminal peptides. Despite the high sequence homology, the isoforms show differences in cellular distribution, in localization to nuclear substructures, and in their interaction with nuclear proteins through yet unknown mechanisms. In this study, we used EGFP-fusion constructs that express truncated or mutated versions of myosin IC isoforms to detect regions that are involved in isoform-specific localization. We identified two nucleolar localization signals (NoLS). One NoLS is located in the myosin IC isoform B specific N-terminal peptide, the second NoLS is located upstream of the neck region within the head domain. We demonstrate that both NoLS are functional and necessary for nucleolar localization of specifically myosin IC isoform B. Our data provide a first mechanistic explanation for the observed functional differences between the myosin IC isoforms and are an important step toward our understanding of the underlying mechanisms that regulate the various and distinct functions of myosin IC isoforms. - Highlights: ► Two NoLS have been identified in the myosin IC isoform B sequence. ► Both NoLS are necessary for myosin IC isoform B specific nucleolar localization. ► First mechanistic explanation of functional differences between the isoforms.

What role does performance information play in securing improvement in healthcare? a conceptual framework for levers of change.

Science.gov (United States)

Levesque, Jean-Frederic; Sutherland, Kim

2017-08-28

Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework-one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. A synthesis of published frameworks. The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Myosin VIIa as a common component of cilia and microvilli.

Science.gov (United States)

Wolfrum, U; Liu, X; Schmitt, A; Udovichenko, I P; Williams, D S

1998-01-01

The distribution of myosin VIIa, which is defective or absent in Usher syndrome 1B, was studied in a variety of tissues by immunomicroscopy. The primary aim was to determine whether this putative actin-based mechanoenzyme is a common component of cilia. Previously, it has been proposed that defective ciliary function might be the basis of some forms of Usher syndrome. Myosin VIIa was detected in cilia from cochlear hair cells, olfactory neurons, kidney distal tubules, and lung bronchi. It was also found to cofractionate with the axonemal fraction of retinal photoreceptor cells. Immunolabeling appeared most concentrated in the periphery of the transition zone of the cilia. This general presence of a myosin in cilia is surprising, given that cilia are dominated by microtubules, and not actin filaments. In addition to cilia, myosin VIIa was also found in actin-rich microvilli of different types of cell. We conclude that myosin VIIa is a common component of cilia and microvilli.

Fast and slow myosins as markers of muscle injury.

Science.gov (United States)

Guerrero, M; Guiu-Comadevall, M; Cadefau, J A; Parra, J; Balius, R; Estruch, A; Rodas, G; Bedini, J L; Cussó, R

2008-07-01

The diagnosis of muscular lesions suffered by athletes is usually made by clinical criteria combined with imaging of the lesion (ultrasonography and/or magnetic resonance) and blood tests to detect the presence of non-specific muscle markers. This study was undertaken to evaluate injury to fast and slow-twitch fibres using specific muscle markers for these fibres. Blood samples were obtained from 51 non-sports people and 38 sportsmen with skeletal muscle injury. Western blood analysis was performed to determine fast and slow myosin and creatine kinase (CK) levels. Skeletal muscle damage was diagnosed by physical examination, ultrasonography and magnetic resonance and biochemical markers. The imaging tests were found to be excellent for detecting and confirming grade II and III lesions. However, grade I lesions were often unconfirmed by these techniques. Grade I lesions have higher levels of fast myosin than slow myosin with a very small increase in CK levels. Grade II and III lesions have high values of both fast and slow myosin. The evaluation of fast and slow myosin in the blood 48 h after the lesion occurs is a useful aid for the detection of type I lesions in particular, since fast myosin is an exclusive skeletal muscle marker. The correct diagnosis of grade I lesions can prevent progression of the injury in athletes undergoing continual training sessions and competitions, thus aiding sports physicians in their decision making.

Biased Brownian motion mechanism for processivity and directionality of single-headed myosin-VI.

Science.gov (United States)

Iwaki, Mitsuhiro; Iwane, Atsuko Hikikoshi; Ikebe, Mitsuo; Yanagida, Toshio

2008-01-01

Conventional form to function as a vesicle transporter is not a 'single molecule' but a coordinated 'two molecules'. The coordinated two molecules make it complicated to reveal its mechanism. To overcome the difficulty, we adopted a single-headed myosin-VI as a model protein. Myosin-VI is an intracellular vesicle and organelle transporter that moves along actin filaments in a direction opposite to most other known myosin classes. The myosin-VI was expected to form a dimer to move processively along actin filaments with a hand-over-hand mechanism like other myosin organelle transporters. However, wild-type myosin-VI was demonstrated to be monomer and single-headed, casting doubt on its processivity. Using single molecule techniques, we show that green fluorescent protein (GFP)-fused single-headed myosin-VI does not move processively. However, when coupled to a 200 nm polystyrene bead (comparable to an intracellular vesicle in size) at a ratio of one head per bead, single-headed myosin-VI moves processively with large (40 nm) steps. Furthermore, we found that a single-headed myosin-VI-bead complex moved more processively in a high-viscous solution (40-fold higher than water) similar to cellular environment. Because diffusion of the bead is 60-fold slower than myosin-VI heads alone in water, we propose a model in which the bead acts as a diffusional anchor for the myosin-VI, enhancing the head's rebinding following detachment and supporting processive movement of the bead-monomer complex. This investigation will help us understand how molecular motors utilize Brownian motion in cells.

The Kinetics of Myosin Light Chain Kinase Activation of Smooth Muscle Myosin in an In Vitro Model System

OpenAIRE

Hong, Feng; Facemyer, Kevin C.; Carter, Michael S.; Jackson, Del R.; Haldeman, Brian D.; Ruana, Nick; Sutherland, Cindy; Walsh, Michael P.; Cremo, Christine R.; Baker, Josh E.

2013-01-01

During activation of smooth muscle contraction, one myosin light chain kinase (MLCK) molecule rapidly phosphorylates many smooth muscle myosin (SMM) molecules, suggesting that muscle activation rates are influenced by the kinetics of MLCK-SMM interactions. To determine the rate-limiting step underlying activation of SMM by MLCK, we measured the kinetics of calcium-calmodulin (Ca2+-CaM)-MLCK-mediated SMM phosphorylation and the corresponding initiation of SMM-based F-actin motility in an in vi...

Jan Lever: Challenging the Role of Typological Thinking in Reformational Views of Biology

NARCIS (Netherlands)

Cook, Harry; Flipse, A.C.

2017-01-01

This essay analyzes the view of evolution of Jan Lever (1922–2010), founder of the biology department at the Vrije Universiteit Amsterdam, and compares his view with those of J.H. Diemer and H. Dooyeweerd. Together with Dooyeweerd, Lever wrote a series of chapters on the species concept in

A Role for Myosin Va in Human Cytomegalovirus Nuclear Egress.

Science.gov (United States)

Wilkie, Adrian R; Sharma, Mayuri; Pesola, Jean M; Ericsson, Maria; Fernandez, Rosio; Coen, Donald M

2018-03-15

Herpesviruses replicate and package their genomes into capsids in replication compartments within the nuclear interior. Capsids then move to the inner nuclear membrane for envelopment and release into the cytoplasm in a process called nuclear egress. We previously found that nuclear F-actin is induced upon infection with the betaherpesvirus human cytomegalovirus (HCMV) and is important for nuclear egress and capsid localization away from replication compartment-like inclusions toward the nuclear rim. Despite these and related findings, it has not been shown that any specific motor protein is involved in herpesvirus nuclear egress. In this study, we have investigated whether the host motor protein, myosin Va, could be fulfilling this role. Using immunofluorescence microscopy and coimmunoprecipitation, we observed associations between a nuclear population of myosin Va and the viral major capsid protein, with both concentrating at the periphery of replication compartments. Immunoelectron microscopy showed that nearly 40% of assembled nuclear capsids associate with myosin Va. We also found that myosin Va and major capsid protein colocalize with nuclear F-actin. Importantly, antagonism of myosin Va with RNA interference or a dominant negative mutant revealed that myosin Va is important for the efficient production of infectious virus, capsid accumulation in the cytoplasm, and capsid localization away from replication compartment-like inclusions toward the nuclear rim. Our results lead us to suggest a working model whereby human cytomegalovirus capsids associate with myosin Va for movement from replication compartments to the nuclear periphery during nuclear egress. IMPORTANCE Little is known regarding how newly assembled and packaged herpesvirus capsids move from the nuclear interior to the periphery during nuclear egress. While it has been proposed that an actomyosin-based mechanism facilitates intranuclear movement of alphaherpesvirus capsids, a functional role for

Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses.

Science.gov (United States)

Gutman, Andrea L; Nett, Kelle E; Cosme, Caitlin V; Worth, Wensday R; Gupta, Subhash C; Wemmie, John A; LaLumiere, Ryan T

2017-06-21

The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship

Effects of orbitofrontal cortex lesions on autoshaped lever pressing and reversal learning.

Science.gov (United States)

Chang, Stephen E

2014-10-15

A cue associated with a rewarding event can trigger behavior towards the cue itself due to the cue acquiring incentive value through its pairing with the rewarding outcome (i.e., sign-tracking). For example, rats will approach, press, and attempt to "consume" a retractable lever conditioned stimulus (CS) that signals delivery of a food unconditioned stimulus (US). Attending to food-predictive CSs is important when seeking out food, and it is just as important to be able to modify one's behavior when the relationships between CSs and USs are changed. Using a discriminative autoshaping procedure with lever CSs, the present study investigated the effects of orbitofrontal cortex (OFC) lesions on sign-tracking and reversal learning. Insertion of one lever was followed by sucrose delivery upon retraction, and insertion of another lever was followed by nothing. After the acquisition phase, the contingencies between the levers and outcomes were reversed. Bilateral OFC lesions had no effect on the acquisition of sign-tracking. However, OFC-lesioned rats showed substantial deficits in acquiring sign-tracking compared to sham-lesioned rats once the stimulus-outcome contingencies were reversed. Over the course of reversal learning, OFC-lesioned rats were able to reach comparable levels of sign-tracking as sham-lesioned rats. These findings suggest that OFC is not necessary for the ability of a CS to acquire incentive value and provide more evidence that OFC is critical for modifying behavior appropriately following a change in stimulus-outcome contingencies. Copyright © 2014 Elsevier B.V. All rights reserved.

The Intriguing Dual Lattices of the Myosin Filaments in Vertebrate Striated Muscles: Evolution and Advantage

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Pradeep K. Luther

2014-12-01

Full Text Available Myosin filaments in vertebrate striated muscle have a long roughly cylindrical backbone with cross-bridge projections on the surfaces of both halves except for a short central bare zone. In the middle of this central region the filaments are cross-linked by the M-band which holds them in a well-defined hexagonal lattice in the muscle A-band. During muscular contraction the M-band-defined rotation of the myosin filaments around their long axes influences the interactions that the cross-bridges can make with the neighbouring actin filaments. We can visualise this filament rotation by electron microscopy of thin cross-sections in the bare-region immediately adjacent to the M-band where the filament profiles are distinctly triangular. In the muscles of teleost fishes, the thick filament triangular profiles have a single orientation giving what we call the simple lattice. In other vertebrates, for example all the tetrapods, the thick filaments have one of two orientations where the triangles point in opposite directions (they are rotated by 60° or 180° according to set rules. Such a distribution cannot be developed in an ordered fashion across a large 2D lattice, but there are small domains of superlattice such that the next-nearest neighbouring thick filaments often have the same orientation. We believe that this difference in the lattice forms can lead to different contractile behaviours. Here we provide a historical review, and when appropriate cite recent work related to the emergence of the simple and superlattice forms by examining the muscles of several species ranging back to primitive vertebrates and we discuss the functional differences that the two lattice forms may have.

Dynamics of myosin II organization into cortical contractile networks and fibers

Science.gov (United States)

Nie, Wei; Wei, Ming-Tzo; Ou-Yang, Daniel; Jedlicka, Sabrina; Vavylonis, Dimitrios

2014-03-01

The morphology of adhered cells critically depends on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin which disrupts actomyosin stress fibers. Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared them to studies by other groups. This analysis suggested that the following processes contribute to the assembly of cortical actomyosin into fibers: random myosin mini-filament assembly and disassembly along the cortex; myosin mini-filament aligning and contraction; stabilization of cortical myosin upon increasing contractile tension. We developed simple numerical simulations that include those processes. The results of simulations of cells at steady state and in response to blebbistatin capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness.

Unconstrained steps of myosin VI appear longest among known molecular motors.

Science.gov (United States)

Ali, M Yusuf; Homma, Kazuaki; Iwane, Atsuko Hikikoshi; Adachi, Kengo; Itoh, Hiroyasu; Kinosita, Kazuhiko; Yanagida, Toshio; Ikebe, Mitsuo

2004-06-01

Myosin VI is a two-headed molecular motor that moves along an actin filament in the direction opposite to most other myosins. Previously, a single myosin VI molecule has been shown to proceed with steps that are large compared to its neck size: either it walks by somehow extending its neck or one head slides along actin for a long distance before the other head lands. To inquire into these and other possible mechanism of motility, we suspended an actin filament between two plastic beads, and let a single myosin VI molecule carrying a bead duplex move along the actin. This configuration, unlike previous studies, allows unconstrained rotation of myosin VI around the right-handed double helix of actin. Myosin VI moved almost straight or as a right-handed spiral with a pitch of several micrometers, indicating that the molecule walks with strides slightly longer than the actin helical repeat of 36 nm. The large steps without much rotation suggest kinesin-type walking with extended and flexible necks, but how to move forward with flexible necks, even under a backward load, is not clear. As an answer, we propose that a conformational change in the lifted head would facilitate landing on a forward, rather than backward, site. This mechanism may underlie stepping of all two-headed molecular motors including kinesin and myosin V.

Myosin light chain kinase phosphorylation in tracheal smooth muscle

International Nuclear Information System (INIS)

Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

1990-01-01

Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

Actin-myosin network is required for proper assembly of influenza virus particles

Energy Technology Data Exchange (ETDEWEB)

Kumakura, Michiko; Kawaguchi, Atsushi, E-mail: ats-kawaguchi@md.tsukuba.ac.jp; Nagata, Kyosuke, E-mail: knagata@md.tsukuba.ac.jp

2015-02-15

Actin filaments are known to play a central role in cellular dynamics. After polymerization of actin, various actin-crosslinking proteins including non-muscle myosin II facilitate the formation of spatially organized actin filament networks. The actin-myosin network is highly expanded beneath plasma membrane. The genome of influenza virus (vRNA) replicates in the cell nucleus. Then, newly synthesized vRNAs are nuclear-exported to the cytoplasm as ribonucleoprotein complexes (vRNPs), followed by transport to the beneath plasma membrane where virus particles assemble. Here, we found that, by inhibiting actin-myosin network formation, the virus titer tends to be reduced and HA viral spike protein is aggregated on the plasma membrane. These results indicate that the actin-myosin network plays an important role in the virus formation. - Highlights: • Actin-myosin network is important for the influenza virus production. • HA forms aggregations at the plasma membrane in the presence of blebbistatin. • M1 is recruited to the budding site through the actin-myosin network.

Actin-myosin network is required for proper assembly of influenza virus particles

International Nuclear Information System (INIS)

Kumakura, Michiko; Kawaguchi, Atsushi; Nagata, Kyosuke

2015-01-01

Actin filaments are known to play a central role in cellular dynamics. After polymerization of actin, various actin-crosslinking proteins including non-muscle myosin II facilitate the formation of spatially organized actin filament networks. The actin-myosin network is highly expanded beneath plasma membrane. The genome of influenza virus (vRNA) replicates in the cell nucleus. Then, newly synthesized vRNAs are nuclear-exported to the cytoplasm as ribonucleoprotein complexes (vRNPs), followed by transport to the beneath plasma membrane where virus particles assemble. Here, we found that, by inhibiting actin-myosin network formation, the virus titer tends to be reduced and HA viral spike protein is aggregated on the plasma membrane. These results indicate that the actin-myosin network plays an important role in the virus formation. - Highlights: • Actin-myosin network is important for the influenza virus production. • HA forms aggregations at the plasma membrane in the presence of blebbistatin. • M1 is recruited to the budding site through the actin-myosin network

Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis.

Directory of Open Access Journals (Sweden)

Juliane Bremer

2016-11-01

Full Text Available During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues. How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood. Using live cell imaging in zebrafish, we show that as motor axons exit from the spinal cord and extend through extracellular matrix produced by adjacent notochord cells, these cells shift several cell diameters caudally. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We find that this alignment requires myosin phosphatase activity within motoneurons, and that mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation causing a displacement between motoneuron cell bodies and their axons. Thus, we demonstrate that spinal motoneurons fine-tune their position during axonogenesis and we identify the myosin II regulatory network as a key regulator.

Myosin content of individual human muscle fibers isolated by laser capture microdissection.

Science.gov (United States)

Stuart, Charles A; Stone, William L; Howell, Mary E A; Brannon, Marianne F; Hall, H Kenton; Gibson, Andrew L; Stone, Michael H

2016-03-01

Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as α-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. Copyright © 2016 the American Physiological Society.

Task-oriented control of Single-Master Multi-Slave Manipulator System

International Nuclear Information System (INIS)

Kosuge, Kazuhiro; Ishikawa, Jun; Furuta, Katsuhisa; Hariki, Kazuo; Sakai, Masaru.

1994-01-01

A master-slave manipulator system, in general, consists of a master arm manipulated by a human and a slave arm used for real tasks. Some tasks, such as manipulation of a heavy object, etc., require two or more slave arms operated simultaneously. A Single-Master Multi-Slave Manipulator System consists of a master arm with six degrees of freedom and two or more slave arms, each of which has six or more degrees of freedom. In this system, a master arm controls the task-oriented variables using Virtual Internal Model (VIM) based on the concept of 'Task-Oriented Control'. VIM is a reference model driven by sensory information and used to describe the desired relation between the motion of a master arm and task-oriented variables. The motion of slave arms are controlled based on the task oriented variables generated by VIM and tailors the system to meet specific tasks. A single-master multi-slave manipulator system, having two slave arms, is experimentally developed and illustrates the concept. (author)

Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

Science.gov (United States)

Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

2003-05-01

Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance

Myosin VIII regulates protonemal patterning and developmental timing in the moss Physcomitrella patens.

Science.gov (United States)

Wu, Shu-Zon; Ritchie, Julie A; Pan, Ai-Hong; Quatrano, Ralph S; Bezanilla, Magdalena

2011-09-01

Plants have two classes of myosins. While recent work has focused on class XI myosins showing that myosin XI is responsible for organelle motility and cytoplasmic streaming, much less is known about the role of myosin VIII in plant growth and development. We have used a combination of RNAi and insertional knockouts to probe myosin VIII function in the moss Physcomitrella patens. We isolated Δmyo8ABCDE plants demonstrating that myosin VIII is not required for plant viability. However, myosin VIII mutants are smaller than wild-type plants in part due to a defect in cell size. Additionally, Δmyo8ABCDE plants produce more side branches and form gametophores much earlier than wild-type plants. In the absence of nutrient media, Δmyo8ABCDE plants exhibit significant protonemal patterning defects, including highly curved protonemal filaments, morphologically defective side branches, as well as an increase in the number of branches. Exogenous auxin partially rescues protonemal defects in Δmyo8ABCDE plants grown in the absence of nutrients. This result, together with defects in protonemal branching, smaller caulonemal cells, and accelerated development in the Δmyo8ABCDE plants, suggests that myosin VIII is involved in hormone homeostasis in P. patens.

Structural insight into the UNC-45–myosin complex

DEFF Research Database (Denmark)

Fratev, Filip; Jonsdottir, Svava Osk; Pajeva, Ilza

2013-01-01

The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45–myosin complex using various...... is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosinactin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15–16 hypertrophic cardiomyopathy...... mutations and provide directions for drug targeting. © 2013 Wiley Periodicals, Inc....

Three-dimensional stochastic model of actin–myosin binding in the sarcomere lattice

Energy Technology Data Exchange (ETDEWEB)

Mijailovich, Srboljub M.; Kayser-Herold, Oliver; Stojanovic, Boban; Nedic, Djordje; Irving, Thomas C.; Geeves, MA (Harvard); (IIT); (U. Kent); (Kragujevac)

2016-11-18

The effect of molecule tethering in three-dimensional (3-D) space on bimolecular binding kinetics is rarely addressed and only occasionally incorporated into models of cell motility. The simplest system that can quantitatively determine this effect is the 3-D sarcomere lattice of the striated muscle, where tethered myosin in thick filaments can only bind to a relatively small number of available sites on the actin filament, positioned within a limited range of thermal movement of the myosin head. Here we implement spatially explicit actomyosin interactions into the multiscale Monte Carlo platform MUSICO, specifically defining how geometrical constraints on tethered myosins can modulate state transition rates in the actomyosin cycle. The simulations provide the distribution of myosin bound to sites on actin, ensure conservation of the number of interacting myosins and actin monomers, and most importantly, the departure in behavior of tethered myosin molecules from unconstrained myosin interactions with actin. In addition, MUSICO determines the number of cross-bridges in each actomyosin cycle state, the force and number of attached cross-bridges per myosin filament, the range of cross-bridge forces and accounts for energy consumption. At the macroscopic scale, MUSICO simulations show large differences in predicted force-velocity curves and in the response during early force recovery phase after a step change in length comparing to the two simplest mass action kinetic models. The origin of these differences is rooted in the different fluxes of myosin binding and corresponding instantaneous cross-bridge distributions and quantitatively reflects a major flaw of the mathematical description in all mass action kinetic models. Consequently, this new approach shows that accurate recapitulation of experimental data requires significantly different binding rates, number of actomyosin states, and cross-bridge elasticity than typically used in mass action kinetic models to

The expression of myosin genes in developing skeletal muscle in the mouse embryo

International Nuclear Information System (INIS)

Lyons, G.E.; Ontell, M.; Cox, R.; Sassoon, D.; Buckingham, M.

1990-01-01

Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta-cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and acculumation

The C-Lever Project: Haptics for Automotive Applications

NARCIS (Netherlands)

Garcia Canseco, E.; Ayemlong Fokem, A.; Serrarens, A.F.A.; Steinbuch, M.; Stigter, H.

2010-01-01

The goal of this project is to research the effectiveness of a controlled haptic force feedback shift lever that can accurately reproduce the behavior of a manual gear shift during driving, and that can also be used to control interior and comfort functions in the car.

Oxidation of myosin by haem proteins generates myosin radicals and protein cross-links

DEFF Research Database (Denmark)

Lametsch, Marianne Lund; Luxford, Catherine; Skibsted, Leif Horsfelt

2008-01-01

of thiyl and tyrosyl radicals is consistent with the observed consumption of cysteine and tyrosine residues, the detection of di-tyrosine by HPLC and the detection of both reducible (disulfide bond) and non-reducible cross-links between myosin molecules by SDS/PAGE. The time course of radical formation...

Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II

Directory of Open Access Journals (Sweden)

Drescher Uwe

2010-06-01

Full Text Available Abstract Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A. It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear. Results In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK and myosin light chain kinase (MLCK, which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points. Conclusions Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.

Adult fast myosin pattern and Ca2+-induced slow myosin pattern in primary skeletal muscle culture

Science.gov (United States)

Kubis, Hans-Peter; Haller, Ernst-August; Wetzel, Petra; Gros, Gerolf

1997-01-01

A primary muscle cell culture derived from newborn rabbit muscle and growing on microcarriers in suspension was established. When cultured for several weeks, the myotubes in this model develop the completely adult pattern of fast myosin light and heavy chains. When Ca2+ ionophore is added to the culture medium on day 11, raising intracellular [Ca2+] about 10-fold, the myotubes develop to exhibit properties of an adult slow muscle by day 30, expressing slow myosin light as well as heavy chains, elevated citrate synthase, and reduced lactate dehydrogenase. The remarkable plasticity of these myotubes becomes apparent, when 8 days after withdrawal of the ionophore a marked slow-to-fast transition, as judged from the expression of isomyosins and metabolic enzymes, occurs. PMID:9108130

Apparatus for connecting an element attached to a metallic wire to an interior tube in a core drill

Energy Technology Data Exchange (ETDEWEB)

1970-04-17

A locking device consists of at least one lever pivotable around an axis transversal to the axis of the core drill and mounted on the upper end of the core tube. A first arm oriented upward is intended to pivot during lowering of the wire line and to engage on the core tube, so that the core tube can be lifted by the wire line. A second arm prevents lifting of the core tube during drilling. The second arm also releases the core tube, after the wire line has been firmly attached and locked onto the core tube.

Catalytic strategy used by the myosin motor to hydrolyze ATP.

Science.gov (United States)

Kiani, Farooq Ahmad; Fischer, Stefan

2014-07-22

Myosin is a molecular motor responsible for biological motions such as muscle contraction and intracellular cargo transport, for which it hydrolyzes adenosine 5'-triphosphate (ATP). Early steps of the mechanism by which myosin catalyzes ATP hydrolysis have been investigated, but still missing are the structure of the final ADP·inorganic phosphate (Pi) product and the complete pathway leading to it. Here, a comprehensive description of the catalytic strategy of myosin is formulated, based on combined quantum-classical molecular mechanics calculations. A full exploration of catalytic pathways was performed and a final product structure was found that is consistent with all experiments. Molecular movies of the relevant pathways show the different reorganizations of the H-bond network that lead to the final product, whose γ-phosphate is not in the previously reported HPγO4(2-) state, but in the H2PγO4(-) state. The simulations reveal that the catalytic strategy of myosin employs a three-pronged tactic: (i) Stabilization of the γ-phosphate of ATP in a dissociated metaphosphate (PγO3(-)) state. (ii) Polarization of the attacking water molecule, to abstract a proton from that water. (iii) Formation of multiple proton wires in the active site, for efficient transfer of the abstracted proton to various product precursors. The specific role played in this strategy by each of the three loops enclosing ATP is identified unambiguously. It explains how the precise timing of the ATPase activation during the force generating cycle is achieved in myosin. The catalytic strategy described here for myosin is likely to be very similar in most nucleotide hydrolyzing enzymes.

Calibration Procedures in Mid Format Camera Setups

Science.gov (United States)

Pivnicka, F.; Kemper, G.; Geissler, S.

2012-07-01

A growing number of mid-format cameras are used for aerial surveying projects. To achieve a reliable and geometrically precise result also in the photogrammetric workflow, awareness on the sensitive parts is important. The use of direct referencing systems (GPS/IMU), the mounting on a stabilizing camera platform and the specific values of the mid format camera make a professional setup with various calibration and misalignment operations necessary. An important part is to have a proper camera calibration. Using aerial images over a well designed test field with 3D structures and/or different flight altitudes enable the determination of calibration values in Bingo software. It will be demonstrated how such a calibration can be performed. The direct referencing device must be mounted in a solid and reliable way to the camera. Beside the mechanical work especially in mounting the camera beside the IMU, 2 lever arms have to be measured in mm accuracy. Important are the lever arms from the GPS Antenna to the IMU's calibrated centre and also the lever arm from the IMU centre to the Camera projection centre. In fact, the measurement with a total station is not a difficult task but the definition of the right centres and the need for using rotation matrices can cause serious accuracy problems. The benefit of small and medium format cameras is that also smaller aircrafts can be used. Like that, a gyro bases stabilized platform is recommended. This causes, that the IMU must be mounted beside the camera on the stabilizer. The advantage is, that the IMU can be used to control the platform, the problematic thing is, that the IMU to GPS antenna lever arm is floating. In fact we have to deal with an additional data stream, the values of the movement of the stabiliser to correct the floating lever arm distances. If the post-processing of the GPS-IMU data by taking the floating levers into account, delivers an expected result, the lever arms between IMU and camera can be applied

Large Signal Circuit Model of Two-Section Gain Lever Quantum Dot Laser

International Nuclear Information System (INIS)

Horri Ashkan; Mirmoeini Seyedeh Zahra; Faez Rahim

2012-01-01

An equivalent circuit model for the design and analysis of two-section gain lever quantum dot (QD) laser is presented. This model is based on the three level rate equations with two independent carrier populations and a single longitudinal optical mode. By using the presented model, the effect of gain lever on QD laser performances is investigated. The results of simulation show that the main characteristics of laser such as threshold current, transient response, output power and modulation response are affected by differential gain ratios between the two-sections

The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle.

Science.gov (United States)

Cooke, Roger

2011-03-01

Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the "furnace" that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430-435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

The jaw is a second-class lever in Pedetes capensis (Rodentia: Pedetidae

Directory of Open Access Journals (Sweden)

Philip G. Cox

2017-08-01

Full Text Available The mammalian jaw is often modelled as a third-class lever for the purposes of biomechanical analyses, owing to the position of the resultant muscle force between the jaw joint and the teeth. However, it has been proposed that in some rodents the jaws operate as a second-class lever during distal molar bites, owing to the rostral position of the masticatory musculature. In particular, the infraorbital portion of the zygomatico-mandibularis (IOZM has been suggested to be of major importance in converting the masticatory system from a third-class to a second-class lever. The presence of the IOZM is diagnostic of the hystricomorph rodents, and is particularly well-developed in Pedetes capensis, the South African springhare. In this study, finite element analysis (FEA was used to assess the lever mechanics of the springhare masticatory system, and to determine the function of the IOZM. An FE model of the skull of P. capensis was constructed and loaded with all masticatory muscles, and then solved for biting at each tooth in turn. Further load cases were created in which each masticatory muscle was removed in turn. The analyses showed that the mechanical advantage of the springhare jaws was above one at all molar bites and very close to one during the premolar bite. Removing the IOZM or masseter caused a drop in mechanical advantage at all bites, but affected strain patterns and cranial deformation very little. Removing the ZM had only a small effect on mechanical advantage, but produced a substantial reduction in strain and deformation across the skull. It was concluded that the masticatory system of P. capensis acts as a second class lever during bites along almost the entire cheek tooth row. The IOZM is clearly a major contributor to this effect, but the masseter also has a part to play. The benefit of the IOZM is that it adds force without substantially contributing to strain or deformation of the skull. This may help explain why the

Technology-supported training of arm-hand skills in stroke

NARCIS (Netherlands)

Timmermans, A.A.A.

2010-01-01

Impaired arm-hand performance is a serious consequence of stroke that is associated with reduced self-efficacy and poor quality of life. Task-oriented arm training is a therapy approach that is known to improve skilled arm-hand performance, even in chronic stages after stroke. At the start of this

Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

International Nuclear Information System (INIS)

Bhadriraju, Kiran; Hansen, Linda K.

2004-01-01

Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

Sibelius: Luonnotar. Chevauchee nocturne et lever du soleil / Pierre Gervasoni

Index Scriptorium Estoniae

Gervasoni, Pierre

1996-01-01

Uuest heliplaadist "Sibelius: Luonnotar. Chevauchee nocturne et lever du soleil. 4 Legendes. Orchestre Philharmonique Royal de Stockholm, Paavo Järvi. Virgin Classics 545 213-2 (CD:167F). 1996. TT: 1h 13'22"

Study of the mechanism of clamping and detachment of a core sample by core lever lifters

Energy Technology Data Exchange (ETDEWEB)

Barabashkin, I I; Mizyakin, V M; Nikitin, S V

1981-01-01

Geometric dimensions of the basic elements of a core lifter should be determined depending on the clamping conditions. The changes should be determined depending on the conditions of the core sample diameter, critical angle between the lever and the core samples in the necessary depth of submersion of the contact edge of the lever into its surface. The core lifter KTsRZ-80 with eccentric core reception makes it possible to arrange more efficiently the core removing elements on the edge of the band. The use of the core lifters with eccentric plan of arrangement of the levers and their optimal length increases the removal of the core sample.

Localization of Myosin and Actin in the Pelage and Whisker Hair Follicles of Rat

International Nuclear Information System (INIS)

Morioka, Kiyokazu; Matsuzaki, Toshiyuki; Takata, Kuniaki

2006-01-01

The combined effects of myosin II and actin enable muscle and nonmuscle cells to generate forces required for muscle contraction, cell division, cell migration, cellular morphological changes, the maintenance of cellular tension and polarity, and so on. However, except for the case of muscle contraction, the details are poorly understood. We focus on nonmuscle myosin and actin in the formation and maintenance of hair and skin, which include highly active processes in mammalian life with respect to the cellular proliferation, differentiation, and movement. The localization of nonmuscle myosin II and actin in neonatal rat dorsal skin, mystacial pad, hair follicles, and vibrissal follicles was studied by immunohistochemical technique to provide the basis for the elucidation of the roles of these proteins. Specificities of the antibodies were verified by using samples from the relevant tissues and subjecting them to immunoblotting test prior to morphological analyses. The myosin and actin were abundant and colocalized in the spinous and granular layers but scarce in the basal layer of the dorsal and mystacial epidermis. In hair and vibrissal follicles, nonmuscle myosin and actin were colocalized in the outer root sheath and some hair matrix cells adjoining dermal papillae. In contrast, most areas of the inner root sheath and hair matrix appeared to comprise very small amounts of myosin and actin. Hair shaft may comprise significant myosin during the course of its keratinization. These results suggest that the actin-myosin system plays a part in cell movement, differentiation, protection and other key functions of skin and hair cells

Reduction in beta-myosin heavy chains in stunned myocardium as assessed by nondenaturing gel electrophoresis.

Science.gov (United States)

Garcia, S C; Pomblum, V J; Gams, E; Rupp, H; Schipke, J D

2007-09-01

Myosin plays a key role in the structure and function of cardiac muscle. Three myosin isoenzymes (V(1), V(2), and V(3)) with different ATPase activities have been identified in mammalian ventricles based on their heavy chain constituents. The relative amount of myosin isoenzymes changes under physiological and pathological conditions. Until now, myosin isoenzymes have frequently been determined using either tube gel (nondenaturing) polyacrylamide gel electrophoresis (PAGE), or gradient or uniform sodium dodecyl sulfate (denaturing) PAGE. Both methods have disadvantages, e.g., a long running time. We developed, therefore, a uniform, nondenaturing PAGE with slab minigel format for analyzing the myosin isoenzymes in normoxic and stunned rabbit hearts. In normoxic hearts of adult rabbits, V(3) predominated over V(1) (46 vs 41%). In turn, in the stunned hearts, V(1) predominated over V(3) (70 vs 30%), and the heterodimeric V(2) was not anymore detectable. This alteration appears to result from a selective loss of myosin heavy chain (MHC)-beta. In parallel, the biochemical markers troponin I and creatine kinase were increased in the stunned hearts. We suggest that alterations of myosin isoenzymes in stunned myocardium can be monitored with native PAGE. The present analysis of myosin isoenzyme appears thus as a new tool for evaluating defects in MHC dimer formation in postischemic hearts.

Myosins 1 and 6, myosin light chain kinase, actin and microtubules cooperate during antibody-mediated internalisation and trafficking of membrane-expressed viral antigens in feline infectious peritonitis virus infected monocytes.

Science.gov (United States)

Dewerchin, Hannah L; Desmarets, Lowiese M; Noppe, Ytse; Nauwynck, Hans J

2014-02-12

Monocytes infected with feline infectious peritonitis virus, a coronavirus, express viral proteins in their plasma membranes. Upon binding of antibodies, these proteins are quickly internalised through a new clathrin- and caveolae-independent internalisation pathway. By doing so, the infected monocytes can escape antibody-dependent cell lysis. In the present study, we investigated which kinases and cytoskeletal proteins are of importance during internalisation and subsequent intracellular transport. The experiments showed that myosin light chain kinase (MLCK) and myosin 1 are crucial for the initiation of the internalisation. With co-localisation stainings, it was found that MLCK and myosin 1 co-localise with antigens even before internalisation started. Myosin 6 co-localised with the internalising complexes during passage through the cortical actin, were it might play a role in moving or disintegrating actin filaments, to overcome the actin barrier. One minute after internalisation started, vesicles had passed the cortical actin, co-localised with microtubules and association with myosin 6 was lost. The vesicles were further transported over the microtubules and accumulated at the microtubule organising centre after 10 to 30 min. Intracellular trafficking over microtubules was mediated by MLCK, myosin 1 and a small actin tail. Since inhibiting MLCK with ML-7 was so efficient in blocking the internalisation pathway, this target can be used for the development of a new treatment for FIPV.

Actin-myosin contractility is responsible for the reduced viability of dissociated human embryonic stem cells.

Science.gov (United States)

Chen, Guokai; Hou, Zhonggang; Gulbranson, Daniel R; Thomson, James A

2010-08-06

Human ESCs are the pluripotent precursor of the three embryonic germ layers. Human ESCs exhibit basal-apical polarity, junctional complexes, integrin-dependent matrix adhesion, and E-cadherin-dependent cell-cell adhesion, all characteristics shared by the epiblast epithelium of the intact mammalian embryo. After disruption of epithelial structures, programmed cell death is commonly observed. If individualized human ESCs are prevented from reattaching and forming colonies, their viability is significantly reduced. Here, we show that actin-myosin contraction is a critical effector of the cell death response to human ESC dissociation. Inhibition of myosin heavy chain ATPase, downregulation of myosin heavy chain, and downregulation of myosin light chain all increase survival and cloning efficiency of individualized human ESCs. ROCK inhibition decreases phosphorylation of myosin light chain, suggesting that inhibition of actin-myosin contraction is also the mechanism through which ROCK inhibitors increase cloning efficiency of human ESCs. Copyright 2010 Elsevier Inc. All rights reserved.

An isoform of myosin XI is responsible for the translocation of endoplasmic reticulum in tobacco cultured BY-2 cells.

Science.gov (United States)

Yokota, Etsuo; Ueda, Shunpei; Tamura, Kentaro; Orii, Hidefumi; Uchi, Satoko; Sonobe, Seiji; Hara-Nishimura, Ikuko; Shimmen, Teruo

2009-01-01

The involvement of myosin XI in generating the motive force for cytoplasmic streaming in plant cells is becoming evident. For a comprehensive understanding of the physiological roles of myosin XI isoforms, it is necessary to elucidate the properties and functions of each isoform individually. In tobacco cultured BY-2 cells, two types of myosins, one composed of 175 kDa heavy chain (175 kDa myosin) and the other of 170 kDa heavy chain (170 kDa myosin), have been identified biochemically and immunocytochemically. From sequence analyses of cDNA clones encoding heavy chains of 175 kDa and 170 kDa myosin, both myosins have been classified as myosin XI. Immunocytochemical studies using a polyclonal antibody against purified 175 kDa myosin heavy chain showed that the 175 kDa myosin is distributed throughout the cytoplasm as fine dots in interphase BY-2 cells. During mitosis, some parts of 175 kDa myosin were found to accumulate in the pre-prophase band (PPB), spindle, the equatorial plane of a phragmoplast and on the circumference of daughter nuclei. In transgenic BY-2 cells, in which an endoplasmic reticulum (ER)-specific retention signal, HDEL, tagged with green fluorescent protein (GFP) was stably expressed, ER showed a similar behaviour to that of 175 kDa myosin. Furthermore, this myosin was co-fractionated with GFP-ER by sucrose density gradient centrifugation. From these findings, it was suggested that the 175 kDa myosin is a molecular motor responsible for translocating ER in BY-2 cells.

Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping.

Science.gov (United States)

Nasser, Helen M; Lafferty, Danielle S; Lesser, Ellen N; Bacharach, Sam Z; Calu, Donna J

2018-01-01

Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

Science.gov (United States)

Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

2017-07-07

A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dynamics of myosin II organization into contractile networks and fibers at the medial cell cortex

Science.gov (United States)

Nie, Wei

The cellular morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of non-muscle myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin (which disrupts actomyosin stress fibers). Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared to studies by other groups. This analysis suggested the following processes: myosin minifilament assembly and disassembly; aligning and contraction; myosin filament stabilization upon increasing contractile tension. Numerical simulations that include those processes capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. We discuss methods to monitor myosin reorganization using non-linear imaging methods.

Native myosin from adult rabbit skeletal muscle: isoenzymes and states of aggregation.

Science.gov (United States)

Morel, J E; D'hahan, N; Taouil, K; Francin, M; Aguilar, A; Dalbiez, J P; Merah, Z; Grussaute, H; Hilbert, B; Ollagnon, F; Selva, G; Piot, F

1998-04-21

The globular heads of skeletal muscle myosin have been shown to exist as isoenzymes S1 (A1) and S1 (A2), and there are also isoforms of the heavy chains. Using capillary electrophoresis, we found two dominant isoenzymes of the whole native myosin molecule, in agreement with what has previously been found by various techniques for native and nondenatured myosin from adult rabbits. Findings about possible states of aggregation of myosin and its heads are contradictory. By analytical ultracentrifugation, we confirmed the existence of a tail-tail dimer. By laser light scattering, we found a head-head dimer in the presence of MgATP. Capillary electrophoresis coupled with analytical ultracentrifugation and laser light scattering led us to refine these results. We found tail-tail dimers in a conventional buffer. We found tail-tail and head-head dimers in the presence of 0.5 mM MgATP and pure head-head dimers in the presence of 6 mM MgATP. All the dimers were homodimers. Naming the dominant isoenzymes of myosin a and b, we observed tail-tail dimers with isoenzyme a (TaTa) and with isoenzyme b (TbTb) and also head-head dimers with isoenzyme a (HaHa) and with isoenzyme b (HbHb).

CALIBRATION PROCEDURES IN MID FORMAT CAMERA SETUPS

Directory of Open Access Journals (Sweden)

F. Pivnicka

2012-07-01

Full Text Available A growing number of mid-format cameras are used for aerial surveying projects. To achieve a reliable and geometrically precise result also in the photogrammetric workflow, awareness on the sensitive parts is important. The use of direct referencing systems (GPS/IMU, the mounting on a stabilizing camera platform and the specific values of the mid format camera make a professional setup with various calibration and misalignment operations necessary. An important part is to have a proper camera calibration. Using aerial images over a well designed test field with 3D structures and/or different flight altitudes enable the determination of calibration values in Bingo software. It will be demonstrated how such a calibration can be performed. The direct referencing device must be mounted in a solid and reliable way to the camera. Beside the mechanical work especially in mounting the camera beside the IMU, 2 lever arms have to be measured in mm accuracy. Important are the lever arms from the GPS Antenna to the IMU's calibrated centre and also the lever arm from the IMU centre to the Camera projection centre. In fact, the measurement with a total station is not a difficult task but the definition of the right centres and the need for using rotation matrices can cause serious accuracy problems. The benefit of small and medium format cameras is that also smaller aircrafts can be used. Like that, a gyro bases stabilized platform is recommended. This causes, that the IMU must be mounted beside the camera on the stabilizer. The advantage is, that the IMU can be used to control the platform, the problematic thing is, that the IMU to GPS antenna lever arm is floating. In fact we have to deal with an additional data stream, the values of the movement of the stabiliser to correct the floating lever arm distances. If the post-processing of the GPS-IMU data by taking the floating levers into account, delivers an expected result, the lever arms between IMU and

Research on the man in the loop control system of the robot arm based on gesture control

Science.gov (United States)

Xiao, Lifeng; Peng, Jinbao

2017-03-01

The Man in the loop control system of the robot arm based on gesture control research complex real-world environment, which requires the operator to continuously control and adjust the remote manipulator, as the background, completes the specific mission human in the loop entire system as the research object. This paper puts forward a kind of robot arm control system of Man in the loop based on gesture control, by robot arm control system based on gesture control and Virtual reality scene feedback to enhance immersion and integration of operator, to make operator really become a part of the whole control loop. This paper expounds how to construct a man in the loop control system of the robot arm based on gesture control. The system is a complex system of human computer cooperative control, but also people in the loop control problem areas. The new system solves the problems that the traditional method has no immersion feeling and the operation lever is unnatural, the adjustment time is long, and the data glove mode wears uncomfortable and the price is expensive.

Excessive Myosin Activity in Mbs Mutants Causes Photoreceptor Movement Out of the Drosophila Eye Disc Epithelium

OpenAIRE

Lee, Arnold; Treisman, Jessica E.

2004-01-01

Neuronal cells must extend a motile growth cone while maintaining the cell body in its original position. In migrating cells, myosin contraction provides the driving force that pulls the rear of the cell toward the leading edge. We have characterized the function of myosin light chain phosphatase, which down-regulates myosin activity, in Drosophila photoreceptor neurons. Mutations in the gene encoding the myosin binding subunit of this enzyme cause photoreceptors to drop out of the eye disc e...

[Effect of freezing and cooking on the texture and electrophoretic pattern of the proteins of octopus arms (Octopus vulgaris)].

Science.gov (United States)

Reyes, Genara; Nirchio, Mauro; Bello, Rafael; Borderías, Javier

2014-09-01

Texture is the most valuable feature in cephalopods. Factors that mainly affect the texture of octopus are: freezing, scalding and cooking. The aim of this study was to assess the effect of freezing, scalding and length of cooking time on the texture and electrophoretic pattern of proteins of octopus arms. Octopuses were trapped near Margarita Island and carried with ice to the laboratory where they were packed and subjected to: a) freezing at -27 degrees C or at -20 degrees C b) scalding c) cooking for 25 min, 35 min or 45 min. Shear force was determined by Kramer cell on strips of octopus arms. SDS-PAGE was done according to the Laemmli method with 12% polyacrilamide gels. A sensory evaluation of the preference of texture was carried out using a hedonic scale of 7-points and a non-trained panel. Octopus texture was not affected by freezing temperature or scalding. Frozen octopus was softer after cooking than fresh. The longer the cooking time was, the softer the octopus was. Myosin heavy chain (MHC) was not significantly affected by scalding or cooking; however large aggregates heavier than MHC, new bands and loss of resolution of the bands appeared. Myosin and paramyosin bands were more affected by freezing prior to cooking.

Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala.

Science.gov (United States)

Lamprecht, R; Margulies, D S; Farb, C R; Hou, M; Johnson, L R; LeDoux, J E

2006-01-01

Learning and memory depend on signaling molecules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the training stimuli were presented in a non-associative manner. Anatomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically implicated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nucleus of the amygdala. When ML-7 was applied without associative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the circuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

Smitin, a novel smooth muscle titin-like protein, interacts with myosin filaments in vivo and in vitro.

Science.gov (United States)

Kim, Kyoungtae; Keller, Thomas C S

2002-01-07

Smooth muscle cells use an actin-myosin II-based contractile apparatus to produce force for a variety of physiological functions, including blood pressure regulation and gut peristalsis. The organization of the smooth muscle contractile apparatus resembles that of striated skeletal and cardiac muscle, but remains much more poorly understood. We have found that avian vascular and visceral smooth muscles contain a novel, megadalton protein, smitin, that is similar to striated muscle titin in molecular morphology, localization in a contractile apparatus, and ability to interact with myosin filaments. Smitin, like titin, is a long fibrous molecule with a globular domain on one end. Specific reactivities of an anti-smitin polyclonal antibody and an anti-titin monoclonal antibody suggest that smitin and titin are distinct proteins rather than differentially spliced isoforms encoded by the same gene. Smitin immunofluorescently colocalizes with myosin in chicken gizzard smooth muscle, and interacts with two configurations of smooth muscle myosin filaments in vitro. In physiological ionic strength conditions, smitin and smooth muscle myosin coassemble into irregular aggregates containing large sidepolar myosin filaments. In low ionic strength conditions, smitin and smooth muscle myosin form highly ordered structures containing linear and polygonal end-to-end and side-by-side arrays of small bipolar myosin filaments. We have used immunogold localization and sucrose density gradient cosedimentation analyses to confirm association of smitin with both the sidepolar and bipolar smooth muscle myosin filaments. These findings suggest that the titin-like protein smitin may play a central role in organizing myosin filaments in the contractile apparatus and perhaps in other structures in smooth muscle cells.

77 FR 9890 - Solicitation of Input From Stakeholders Regarding the Smith-Lever 3(d) Children, Youth, and...

Science.gov (United States)

2012-02-21

... DEPARTMENT OF AGRICULTURE National Institute of Food and Agriculture Solicitation of Input From Stakeholders Regarding the Smith-Lever 3(d) Children, Youth, and Families at Risk Sustainable Community... (Pub. L. 110-246) (FCEA) amended section 3(d) of the Smith-Lever Act (7 U.S.C. 343(d)) to provide the...

Controlled, Rapid Uprighting of Molars: A surprisingly Simple Solution The Pivot Arm Appliance.

Science.gov (United States)

Warise, Timothy R; Galella, Steve A

2015-01-01

In orthodontic cases where the regional anatomy provides limited room for eruption, there is etiologically a higher occurrence of tipped/impacted second molars. Although second molar extraction with third molar replacement is a useful option, the "Pivot Arm Appliance" encourages the uprighting of the second molar as a preferred treatment. The most unique and important attribute of the "Pivot Arm Appliance" is the rotating tube. In cases of access limitation, the disto-occlusal surface of the molar presents as one area that is accessible. Other features of the "Pivot Arm Appliance" include: The position of the rotator tube delivers optimal rotational force through the pivoting action of the tube/arm complex. The "Pivot Arm Appliance" takes advantage of the efficiency and simplicity of a Class I lever system. The anatomical fulcrum being the dense cortical bone located anterior to the ascending ramus. The vertical spring system is compact, reliable and delivers gentle controlled force in rotational direction. The lingual location of the "Pivot Arm Appliance" does not hinder the function of the tongue, impinge on the soft tissue or interfere with normal masticatory function. The ease of placement of the rotator tube and subsequent insertion of the spring. It is well to note the uprighting appliance provides a very useful and practical approach to the unique problem of severely tipped second molars with limited buccal access. The "Pivot Arm Appliance" does not function only in these situations but can be used in all cases of second molar uprighting of a moderate to severe nature.

Interaction of Myosin Phosphatase Target Subunit (MYPT1) with Myosin Phosphatase-RhoA Interacting Protein (MRIP): A Role of Glutamic Acids in the Interaction.

Science.gov (United States)

Lee, Eunhee; Stafford, Walter F

2015-01-01

Scaffold proteins bind to and functionally link protein members of signaling pathways. Interaction of the scaffold proteins, myosin phosphatase target subunit (MYPT1) and myosin phosphatase-RhoA interacting protein (MRIP), causes co-localization of myosin phosphatase and RhoA to actomyosin. To examine biophysical properties of interaction of MYPT1 with MRIP, we employed analytical ultracentrifugation and surface plasmon resonance. In regard to MRIP, its residues 724-837 are sufficient for the MYPT1/MRIP interaction. Moreover, MRIP binds to MYPT1 as either a monomer or a dimer. With respect to MYPT1, its leucine repeat region, LR (residues 991-1030) is sufficient to account for the MYPT1/MRIP interaction. Furthermore, point mutations that replace glutamic acids 998-1000 within LR reduced the binding affinity toward MRIP. This suggests that the glutamic acids of MYPT1 play an important role in the interaction.

Levers for change: philanthropy in select South East Asian countries ...

International Development Research Centre (IDRC) Digital Library (Canada)

2016-04-29

Apr 29, 2016 ... Levers for change: philanthropy in select South East Asian countries ... the low donor awareness of societal needs and the lack of donor education and skills development. ... Tourism is an important driver of economic growth throughout Southeast Asia. ... Supporting sustainable economic growth in ASEAN.

Myosin-Powered Membrane Compartment Drives Cytoplasmic Streaming, Cell Expansion and Plant Development.

Science.gov (United States)

Peremyslov, Valera V; Cole, Rex A; Fowler, John E; Dolja, Valerian V

2015-01-01

Using genetic approaches, particle image velocimetry and an inert tracer of cytoplasmic streaming, we have made a mechanistic connection between the motor proteins (myosins XI), cargo transported by these motors (distinct endomembrane compartment defined by membrane-anchored MyoB receptors) and the process of cytoplasmic streaming in plant cells. It is shown that the MyoB compartment in Nicotiana benthamiana is highly dynamic moving with the mean velocity of ~3 μm/sec. In contrast, Golgi, mitochondria, peroxisomes, carrier vesicles and a cytosol flow tracer share distinct velocity profile with mean velocities of 0.6-1.5 μm/sec. Dominant negative inhibition of the myosins XI or MyoB receptors using overexpression of the N. benthamiana myosin cargo-binding domain or MyoB myosin-binding domain, respectively, resulted in velocity reduction for not only the MyoB compartment, but also each of the tested organelles, vesicles and cytoplasmic streaming. Furthermore, the extents of this reduction were similar for each of these compartments suggesting that MyoB compartment plays primary role in cytosol dynamics. Using gene knockout analysis in Arabidopsis thaliana, it is demonstrated that inactivation of MyoB1-4 results in reduced velocity of mitochondria implying slower cytoplasmic streaming. It is also shown that myosins XI and MyoB receptors genetically interact to contribute to cell expansion, plant growth, morphogenesis and proper onset of flowering. These results support a model according to which myosin-dependent, MyoB receptor-mediated transport of a specialized membrane compartment that is conserved in all land plants drives cytoplasmic streaming that carries organelles and vesicles and facilitates cell growth and plant development.

Manipulator arm for a nuclear reactor vessel inspection device

International Nuclear Information System (INIS)

1980-01-01

A manipulator arm for a reactor vessel in-service inspection apparatus is adapted to transport a transducer array for ultrasonic examination of welds at any point in the vessel. The removal of the inspection device from the reactor vessel in an emergency presents a problem where a relatively long manipulator arm is used. This invention provides an improved arm with means for changing the normal orientation of the arm to a shorter one to permit safe removal of the inspection device from the reactor vessel. (author)

Electron Microscopic Recording of the Power and Recovery Strokes of Individual Myosin Heads Coupled with ATP Hydrolysis: Facts and Implications

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Haruo Sugi

2018-05-01

Full Text Available The most straightforward way to get information on the performance of individual myosin heads producing muscle contraction may be to record their movement, coupled with ATP hydrolysis, electron-microscopically using the gas environmental chamber (EC. The EC enables us to visualize and record ATP-induced myosin head movement in hydrated skeletal muscle myosin filaments. When actin filaments are absent, myosin heads fluctuate around a definite neutral position, so that their time-averaged mean position remains unchanged. On application of ATP, myosin heads are found to move away from, but not towards, the bare region, indicating that myosin heads perform a recovery stroke (average amplitude, 6 nm. After exhaustion of ATP, myosin heads return to their neutral position. In the actin–myosin filament mixture, myosin heads form rigor actin myosin linkages, and on application of ATP, they perform a power stroke by stretching adjacent elastic structures because of a limited amount of applied ATP ≤ 10 µM. The average amplitude of the power stroke is 3.3 nm and 2.5 nm at the distal and the proximal regions of the myosin head catalytic domain (CAD, respectively. The power stroke amplitude increases appreciably at low ionic strength, which is known to enhance Ca2+-activated force in muscle. In both the power and recovery strokes, myosin heads return to their neutral position after exhaustion of ATP.

A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction

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Yang Gao

2017-04-01

Full Text Available This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope’s modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity.

The Relationship of Temperature to Strength and Power Production in Intact Human Skeletal Muscle.

Science.gov (United States)

1979-06-01

newton- meters (Nm). The use of the Cybex II isokinetic device has been similarly described by Thorstensson et al. (1976). The peak torque value, or the... isokinetic testing device at four lever arm speeds (0,60,180 and 300*/sec).Maximal knee exter- sions at the different lever arm speeds were evaluated for...Each subject was tested on the Cybex II isokinetic testing device at four lever arm speeds (0,60,180 and $Osec).Maximal knee exten- sions at the

[Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

Science.gov (United States)

Takamatsu, H

1983-06-01

Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

Preparation and Characterization of Myosin Proteins.

Science.gov (United States)

Caldwell, Elizabeth; Eftink, Maurice R.

1985-01-01

Students complete five experimental projects at the end of a senior-level biochemistry course which involves the isolation and characterization of myosin and its water-soluble subfragments. Procedures used and results obtained are provided for such projects as viscosity and ATPase measurements and gel electrophoresis experiments. (JN)

The Role of a Novel Myosin Isoform in Prostate Cancer Metastasis

Science.gov (United States)

2013-10-01

2013 Accepted 14 February 2013 Available online 21 February 2013 Keywords: Myosin IC Isoforms Nucleolar localization signal Nucleolus Nucleus RNA...polymerase I Fibrillarinnt matter & 2013 Elsevier 1016/j.yexcr.2013.02.008 S, nucleolar localization ; No, nucleolus ; N, nucle bovine serum albumin; S...the nucleus, and the nucleolus . In the cytoplasm, myosin IC associ- ates with membranes and is involved in vesicle transport of membrane proteins [2

A Learning Center on the Lever for Young Children.

Science.gov (United States)

Keislar, Evan R.; Luckenbill, Maryann

This document describes a project designed to explore the possibilities of children's learning in mechanics. The principle of the lever, one example of a simple machine, was used in the form of a balance toy. The apparatus was set up as a game in a specially devised learning center. The children made non-verbal predictions as to which way the bar…

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

Science.gov (United States)

Caiozzo, V. J.; Herrick, R. E.; Baldwin, K. M.

1992-01-01

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Preparation of monoclonal antibodies against cardiac myosin and some radiolabelling studies

International Nuclear Information System (INIS)

Bapat, K.; Venkatesh, M.; Pillai, M.R.A.; Sarma, H.D.; Sainis, K.B.

1998-01-01

Monoclonal antibodies were raised against myosin, a specific indicator of myocardial infarction and labelled with 125 I and 99m Tc. Human cardiac myosin was isolated from normal human heart and was used for raising the monoclonal antibodies by the hybridoma technique. Antibody producing clones were identified by ELISA and cloning was done by the limiting dilution technique. Of the 13 clones obtained, 4 were deemed suitable for further studies. The antibodies were grown in ascites, purified, isotyped and their cross reactions with other forms of myosin were estimated. All the clones showed negligible cross reaction with rabbit myosin, but reacted to different extents with bovine skeletal myosin. The most avid antibody Mab-4G4 was chosen for further labelling studies. Mab-4G4 was labelled with 125 I using different oxidising agents such as iodogen, chloramine-T and lactoperoxidase. Purified radioiodinated antibody with radiochemical purity >95% could be obtained by gel filtration. Immunoreactivity was retained as tested by binding to myosin immobilised on a solid support. Mab-4G4 was also labelled with 99m Tc using stannous tartrate as the reducing agent. Radiolabelling yield was ∼60%, the purity was >95% and the immunoreactivity was retained. Both the labelled preparations were tested for bio-distribution in normal and infarcted rats. The activity accumulation in the infarcted region was ∼ 1.5 and 3.5 times as that in normal heart muscle for 125 I and 99m Tc labelled Mab-4G4 respectively. The major problem with the iodinated antibody was the in vivo deiodination resulting in very high percentage of activity in the thyroid. Although the fraction of the total activity associated with the infarcted heart is not very impressive, the fact that the activities with the infarcted and normal hearths are significantly different is heartening. With further optimisation of labelling and use of F(ab)'2 fragments, better delineation of the infarct sites is aspired. (author)

Energy Optimal Trajectories in Human Arm Motion Aiming for Assistive Robots

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Lelai Zhou

2017-01-01

Full Text Available The energy expenditure in human arm has been of great interests for seeking optimal human arm trajectories. This paper presents a new way for calculating metabolic energy consumption of human arm motions. The purpose is to reveal the relationship between the energy consumption and the trajectory of arm motion, and further, the acceleration and arm orientation contributions. Human arm motion in horizontal plane is investigated by virtue of Qualisys motion capture system. The motion data is post-processed by a biomechanical model to obtain the metabolic expenditure. Results on the arm motion kinematics, dynamics and metabolic energy consumption, are included.

Metal cation controls phosphate release in the myosin ATPase.

Science.gov (United States)

Ge, Jinghua; Huang, Furong; Nesmelov, Yuri E

2017-11-01

Myosin is an enzyme that utilizes ATP to produce a conformational change generating a force. The kinetics of the myosin reverse recovery stroke depends on the metal cation complexed with ATP. The reverse recovery stroke is slow for MgATP and fast for MnATP. The metal ion coordinates the γ phosphate of ATP in the myosin active site. It is accepted that the reverse recovery stroke is correlated with the phosphate release; therefore, magnesium "holds" phosphate tighter than manganese. Magnesium and manganese are similar ions in terms of their chemical properties and the shell complexation; hence, we propose to use these ions to study the mechanism of the phosphate release. Analysis of octahedral complexes of magnesium and manganese show that the partial charge of magnesium is higher than that of manganese and the slightly larger size of manganese ion makes its ionic potential smaller. We hypothesize that electrostatics play a role in keeping and releasing the abstracted γ phosphate in the active site, and the stronger electric charge of magnesium ion holds γ phosphate tighter. We used stable myosin-nucleotide analog complex and Raman spectroscopy to examine the effect of the metal cation on the relative position of γ phosphate analog in the active site. We found that in the manganese complex, the γ phosphate analog is 0.01 nm further away from ADP than in the magnesium complex. We conclude that the ionic potential of the metal cation plays a role in the retention of the abstracted phosphate. © 2017 The Protein Society.

K-252a, a novel microbial product, inhibits smooth muscle myosin light chain kinase

International Nuclear Information System (INIS)

Nakanishi, S.; Yamada, K.; Kase, H.; Nakamura, S.; Nonomura, Y.

1988-01-01

Effects of K-252a, purified from the culture broth of Nocardiopsis sp., on the activity of myosin (light chain kinase were investigated. 1) K-252a affected three characteristic properties of chicken gizzard myosin-B, natural actomyosin, to a similar degree: the Ca 2+ -dependent activity of ATPase, superprecipitation, and the phosphorylation of the myosin light chain. 2) K-252a inhibited the activities of the purified myosin light chain kinase and a Ca 2+ -independent form of the enzyme which was constructed by cross-linking of myosin light chain kinase and calmodulin using glutaraldehyde. The degrees of inhibition by 3 x 10 -6 M K-252a were 69 and 48% of the control activities with the purified enzyme and the cross-linked complex, respectively. Chlorpromazine (3 x 10 -4 M), a calmodulin antagonist, inhibited the native enzyme, but not the cross-linked one. These results suggested that K-252a inhibited myosin light chain kinase by direct interaction with the enzyme, whereas chlorpromazine suppressed the enzyme activation by interacting with calmodulin. 3) The inhibition by K-252a of the cross-linked kinase was affected by the concentration of ATP, a phosphate donor. The concentration causing 50% inhibition was two orders magnitude lowere in the presence of 100 μM ATP than in the presence of 2 mM ATP. 4) Kinetic analyses using [γ- 32 P]ATP indicated that the inhibitory mode of K-252a was competitive with respect to ATP. These results suggest that K-252a interacts at the ATP-binding domain of myosin light chain kinase

The Effects of Hsp90α1 Mutations on Myosin Thick Filament Organization.

Science.gov (United States)

He, Qiuxia; Liu, Kechun; Tian, Zhenjun; Du, Shao Jun

2015-01-01

Heat shock protein 90α plays a key role in myosin folding and thick filament assembly in muscle cells. To assess the structure and function of Hsp90α and its potential regulation by post-translational modification, we developed a combined knockdown and rescue assay in zebrafish embryos to systematically analyze the effects of various mutations on Hsp90α function in myosin thick filament organization. DNA constructs expressing the Hsp90α1 mutants with altered putative ATP binding, phosphorylation, acetylation or methylation sites were co-injected with Hsp90α1 specific morpholino into zebrafish embryos. Myosin thick filament organization was analyzed in skeletal muscles of the injected embryos by immunostaining. The results showed that mutating the conserved D90 residue in the Hsp90α1 ATP binding domain abolished its function in thick filament organization. In addition, phosphorylation mimicking mutations of T33D, T33E and T87E compromised Hsp90α1 function in myosin thick filament organization. Similarly, K287Q acetylation mimicking mutation repressed Hsp90α1 function in myosin thick filament organization. In contrast, K206R and K608R hypomethylation mimicking mutations had not effect on Hsp90α1 function in thick filament organization. Given that T33 and T87 are highly conserved residues involved post-translational modification (PTM) in yeast, mouse and human Hsp90 proteins, data from this study could indicate that Hsp90α1 function in myosin thick filament organization is potentially regulated by PTMs involving phosphorylation and acetylation.

Synthesis of lever-blade dampers with enhanced mechanical structure

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Igor I. Sydorenko

2015-03-01

Full Text Available Since the torsion bar represents just an elastic element, the energy dissipation in suspensions problem is highly relevant for its application. Currently in quality of a dissipation device in torsion suspension are used the hydraulic dampers with movable members reciprocating translational motion respectively to the housing or lever-type hydraulic shock absorbers of piston and vane types, with the movable member’s rotational movement respectively to the housing. These dampers are implementing only throttle-valve performance type, associated with these devices’ functional capacities and depending on design constraints. The paper presents a synthesis of innovative lever-blade dampers, whose performance is not related to the value of working chambers inner pressure. Their essential peculiarity relates to the mechanical control loop presence in the structure that determines a close relationship between the performance and the value of the shock absorber movable element displacement relatively to the body. In the process of synthesis carried out tested are the appropriate methods, built on the basis of technical systems’ modeling with modified kinematic graphs. The synthesis results are shown in the form of two structurally implemented samples. Performed is a comparative analysis of the samples with their basic performance determining.

Human myosin VIIa is a very slow processive motor protein on various cellular actin structures.

Science.gov (United States)

Sato, Osamu; Komatsu, Satoshi; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Tanaka, Ryosuke; Mizutani, Takeomi; Watanabe, Tomonobu M; Ikebe, Reiko; Ikebe, Mitsuo

2017-06-30

Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. Although it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7AΔTail/LZ) at the single-molecule level. We found that the HM7AΔTail/LZ moves processively on single actin filaments with a step size of 35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4 s, yielding ∼0.3 s -1 for the mechanical turnover rate; hence, the velocity of HM7AΔTail/LZ was extremely slow, at 11 nm·s -1 We also examined HM7AΔTail/LZ movement on various actin structures in demembranated cells. HM7AΔTail/LZ showed unidirectional movement on actin structures at cell edges, such as lamellipodia and filopodia. However, HM7AΔTail/LZ frequently missed steps on actin tracks and exhibited bidirectional movement at stress fibers, which was not observed with tail-truncated myosin Va. These results suggest that the movement of the human myosin VIIa motor protein is more efficient on lamellipodial and filopodial actin tracks than on stress fibers, which are composed of actin filaments with different polarity, and that the actin structures influence the characteristics of cargo transportation by human myosin VIIa. In conclusion, myosin VIIa movement appears to be suitable for translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Stretch activates myosin light chain kinase in arterial smooth muscle

International Nuclear Information System (INIS)

Barany, K.; Rokolya, A.; Barany, M.

1990-01-01

Stretching of porcine carotid arterial muscle increased the phosphorylation of the 20 kDa myosin light chain from 0.23 to 0.68 mol [32P]phosphate/mol light chain, whereas stretching of phorbol dibutyrate treated muscle increased the phosphorylation from 0.30 to 0.91 mol/mol. Two-dimensional gel electrophoresis followed by two-dimensional tryptic phosphopeptide mapping was used to identify the enzyme involved in the stretch-induced phosphorylation. Quantitation of the [32P]phosphate content of the peptides revealed considerable light chain phosphorylation by protein kinase C only in the phorbol dibutyrate treated arterial muscle, whereas most of the light chain phosphorylation was attributable to myosin light chain kinase. Upon stretch of either the untreated or treated muscle, the total increment in [32P]phosphate incorporation into the light chain could be accounted for by peptides characteristic for myosin light chain kinase catalyzed phosphorylation, demonstrating that the stretch-induced phosphorylation is caused by this enzyme exclusively

Head-head interactions of resting myosin crossbridges in intact frog skeletal muscles, revealed by synchrotron x-ray fiber diffraction.

Directory of Open Access Journals (Sweden)

Kanji Oshima

Full Text Available The intensities of the myosin-based layer lines in the x-ray diffraction patterns from live resting frog skeletal muscles with full thick-thin filament overlap from which partial lattice sampling effects had been removed were analyzed to elucidate the configurations of myosin crossbridges around the thick filament backbone to nanometer resolution. The repeat of myosin binding protein C (C-protein molecules on the thick filaments was determined to be 45.33 nm, slightly longer than that of myosin crossbridges. With the inclusion of structural information for C-proteins and a pre-powerstroke head shape, modeling in terms of a mixed population of regular and perturbed regions of myosin crown repeats along the filament revealed that the myosin filament had azimuthal perturbations of crossbridges in addition to axial perturbations in the perturbed region, producing pseudo-six-fold rotational symmetry in the structure projected down the filament axis. Myosin crossbridges had a different organization about the filament axis in each of the regular and perturbed regions. In the regular region that lacks C-proteins, there were inter-molecular interactions between the myosin heads in axially adjacent crown levels. In the perturbed region that contains C-proteins, in addition to inter-molecular interactions between the myosin heads in the closest adjacent crown levels, there were also intra-molecular interactions between the paired heads on the same crown level. Common features of the interactions in both regions were interactions between a portion of the 50-kDa-domain and part of the converter domain of the myosin heads, similar to those found in the phosphorylation-regulated invertebrate myosin. These interactions are primarily electrostatic and the converter domain is responsible for the head-head interactions. Thus multiple head-head interactions of myosin crossbridges also characterize the switched-off state and have an important role in the regulation

PERFORMANCE ASSESSMENT OF INTEGRATED SENSOR ORIENTATION WITH A LOW-COST GNSS RECEIVER

Directory of Open Access Journals (Sweden)

M. Rehak

2017-08-01

Full Text Available Mapping with Micro Aerial Vehicles (MAVs whose weight does not exceed 5 kg is gaining importance in applications such as corridor mapping, road and pipeline inspections, or mapping of large areas with homogeneous surface structure, e.g. forest or agricultural fields. In these challenging scenarios, integrated sensor orientation (ISO improves effectiveness and accuracy. Furthermore, in block geometry configurations, this mode of operation allows mapping without ground control points (GCPs. Accurate camera positions are traditionally determined by carrier-phase GNSS (Global Navigation Satellite System positioning. However, such mode of positioning has strong requirements on receiver’s and antenna’s performance. In this article, we present a mapping project in which we employ a single-frequency, low-cost (< $100 GNSS receiver on a MAV. The performance of the low-cost receiver is assessed by comparing its trajectory with a reference trajectory obtained by a survey-grade, multi-frequency GNSS receiver. In addition, the camera positions derived from these two trajectories are used as observations in bundle adjustment (BA projects and mapping accuracy is evaluated at check points (ChP. Several BA scenarios are considered with absolute and relative aerial position control. Additionally, the presented experiments show the possibility of BA to determine a camera-antenna spatial offset, so-called lever-arm.

The gearing function of running shoe longitudinal bending stiffness.

Science.gov (United States)

Willwacher, Steffen; König, Manuel; Braunstein, Björn; Goldmann, Jan-Peter; Brüggemann, Gert-Peter

2014-07-01

The purpose of the present study was to investigate whether altered longitudinal bending stiffness (LBS) levels of the midsole of a running shoe lead to a systematic change in lower extremity joint lever arms of the ground reaction force (GRF). Joint moments and GRF lever arms in the sagittal plane were determined from 19 male subjects running at 3.5 m/s using inverse dynamics procedures. LBS was manipulated using carbon fiber insoles of 1.9 mm and 3.2 mm thickness. Increasing LBS led to a significant shift of joint lever arms to a more anterior position. Effects were more pronounced at distal joints. Ankle joint moments were not significantly increased in the presence of higher GRF lever arms when averaged over all subjects. Still, two individual strategies (1: increase ankle joint moments while keeping push-off times almost constant, 2: decrease ankle joint moments and increase push-off times) could be identified in response to increased ankle joint lever arms that might reflect individual differences between subjects with respect to strength capacities or anthropometric characteristics. The results of the present study indicate that LBS systematically influences GRF lever arms of lower extremity joints during the push-off phase in running. Further, individual responses to altered LBS levels could be identified that could aid in finding optimum LBS values for a given individual. Copyright © 2014 Elsevier B.V. All rights reserved.

Picking Robot Arm Trajectory Planning Method

Directory of Open Access Journals (Sweden)

Zhang Zhiyong

2014-01-01

Full Text Available The picking robot arm is scheduled to complete picking tasks in the working space, to overcome the shaking vibration to improve the picking stability, its movement should follow specific consistence trajectory points. Usually we should give definite multiple feature picking points, map their inverse kinematics to the joint space, establish motion equation for the corresponding point in the joint space, then follow these equations motion for the interpolation on the joint so that we can meet the movement requirements. Trajectory planning is decisive significance for accuracy and stability of controlling robot arm. The key issue that picking arm complete picking task will be come true by trajectory planning, namely, robot arm track the desired trajectory. which based on kinematics and statics picking analysis in a joint space according to the requirements of picking tasks, and obtain the position and orientation for picking robot arm, study and calculate the theory of trajectory parameters timely.

Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Fulcher, F. Kent; Smith, Bethany T.; Russ, Misty; Patel, Yashomati M.

2008-01-01

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The experiments described in this report are the first to show a dual role for the myosin IIA isoform specifically in regulating insulin-stimulated glucose uptake in adipocytes. We demonstrate that inhibition of MLCK but not RhoK results in impaired insulin-stimulated glucose uptake. Furthermore, our studies show that insulin specifically stimulates the phosphorylation of the RLC associated with the myosin IIA isoform via MLCK. In time course experiments, we determined that GLUT4 translocates to the plasma membrane prior to myosin IIA recruitment. We further show that recruitment of myosin IIA to the plasma membrane requires that myosin IIA be activated via phosphorylation of the RLC by MLCK. Our findings also reveal that myosin II is required for proper GLUT4-vesicle fusion at the plasma membrane. We show that once at the plasma membrane, myosin II is involved in regulating the intrinsic activity of GLUT4 after insulin stimulation. Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity

Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

Science.gov (United States)

He, Kangmin; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M; Ikebe, Mitsuo

2017-10-20

Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell's leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.

Direct photoaffinity labeling by nucleotides of the apparent catalytic site on the heavy chains of smooth muscle and Acanthamoeba myosins

International Nuclear Information System (INIS)

Maruta, H.; Korn, E.D.

1981-01-01

The heavy chains of Acanthamoeba myosins, IA, IB and II, turkey gizzard myosin, and rabbit skeletal muscle myosin subfragment-1 were specifically labeled by radioactive ATP, ADP, and UTP, each of which is a substrate or product of myosin ATPase activity, when irradiated with uv light at 0 0 C. With UTP, as much as 0.45 mol/mol of Acanthamoeba myosin IA heavy chain and 1 mol/mol of turkey gizzard myosin heavy chain was incorporated. Evidence that the ligands were associated with the catalytic site included the observations that reaction occurred only with nucleotides that are substrates or products of the ATPase activity; that the reaction was blocked by pyrophosphate which is an inhibitor of the ATPase activity; that ATP was bound as ADP; and that label was probably restricted to a single peptide following limited subtilisin proteolysis of labeled Acanthamoeba myosin IA heavy chain and extensive cleavage with CNBr and trypsin of labeled turkey gizzard myosin heavy chain

Myosins and DYNLL1/LC8 in the honey bee (Apis mellifera L.) brain.

Science.gov (United States)

Calábria, Luciana Karen; Peixoto, Pablo Marco Veras; Passos Lima, Andreia Barcelos; Peixoto, Leonardo Gomes; de Moraes, Viviane Rodrigues Alves; Teixeira, Renata Roland; Dos Santos, Claudia Tavares; E Silva, Letícia Oliveira; da Silva, Maria de Fátima Rodrigues; dos Santos, Ana Alice Diniz; Garcia-Cairasco, Norberto; Martins, Antônio Roberto; Espreafico, Enilza Maria; Espindola, Foued Salmen

2011-09-01

Honey bees have brain structures with specialized and developed systems of communication that account for memory, learning capacity and behavioral organization with a set of genes homologous to vertebrate genes. Many microtubule- and actin-based molecular motors are involved in axonal/dendritic transport. Myosin-Va is present in the honey bee Apis mellifera nervous system of the larvae and adult castes and subcastes. DYNLL1/LC8 and myosin-IIb, -VI and -IXb have also been detected in the adult brain. SNARE proteins, such as CaMKII, clathrin, syntaxin, SNAP25, munc18, synaptophysin and synaptotagmin, are also expressed in the honey bee brain. Honey bee myosin-Va displayed ATP-dependent solubility and was associated with DYNLL1/LC8 and SNARE proteins in the membrane vesicle-enriched fraction. Myosin-Va expression was also decreased after the intracerebral injection of melittin and NMDA. The immunolocalization of myosin-Va and -IV, DYNLL1/LC8, and synaptophysin in mushroom bodies, and optical and antennal lobes was compared with the brain morphology based on Neo-Timm histochemistry and revealed a distinct and punctate distribution. This result suggested that the pattern of localization is associated with neuron function. Therefore, our data indicated that the roles of myosins, DYNLL1/LC8, and SNARE proteins in the nervous and visual systems of honey bees should be further studied under different developmental, caste and behavioral conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Commissioner for Inland Revenue V Lever Brothers and Unilever Ltd

African Journals Online (AJOL)

Lever Brothers, the South African tax case that formed the basis of this research, was concerned with determining the source of interest income. In its time, this was one of the landmark cases and established tax principles that were valid for 54 years, until superseded by changes to legislation. The research presented a ...

Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, E; Shi, Q W; Floroff, M; Mickle, D A.G.; Wu, T W; Olley, P M; Jackowski, G

1988-03-25

Human ventricular plasmid library was constructed. The library was screened with the oligonucleotide probe (17-mer) corresponding to a conserve region of myosin light chain 1 near the carboxy terminal. Full length cDNA recombinant plasmid containing 1100 bp insert was isolated. RNA blot hybridization with this insert detected a message of approximately 1500 bp corresponding to the size of VLCl and mRNA. Complete nucleotide sequence of the coding region was determined in M13 subclones using dideoxy chain termination method. With the isolation of this clone (pCD HLVCl), the publication of the complete nucleotide sequence of HVLCl and the predicted secondary structure of this protein will aid in understanding of the biochemistry of myosin and its function in contraction, the evolution of myosin light genes and the genetic, developmental and physiological regulation of myosin genes.

The fungal myosin I is essential for Fusarium toxisome formation.

Directory of Open Access Journals (Sweden)

Guangfei Tang

2018-01-01

Full Text Available Myosin-I molecular motors are proposed to function as linkers between membranes and the actin cytoskeleton in several cellular processes, but their role in the biosynthesis of fungal secondary metabolites remain elusive. Here, we found that the myosin I of Fusarium graminearum (FgMyo1, the causal agent of Fusarium head blight, plays critical roles in mycotoxin biosynthesis. Inhibition of myosin I by the small molecule phenamacril leads to marked reduction in deoxynivalenol (DON biosynthesis. FgMyo1 also governs translation of the DON biosynthetic enzyme Tri1 by interacting with the ribosome-associated protein FgAsc1. Disruption of the ATPase activity of FgMyo1 either by the mutation E420K, down-regulation of FgMyo1 expression or deletion of FgAsc1 results in reduced Tri1 translation. The DON biosynthetic enzymes Tri1 and Tri4 are mainly localized to subcellular structures known as toxisomes in response to mycotoxin induction and the FgMyo1-interacting protein, actin, participates in toxisome formation. The actin polymerization disruptor latrunculin A inhibits toxisome assembly. Consistent with this observation, deletion of the actin-associated proteins FgPrk1 and FgEnd3 also results in reduced toxisome formation. Unexpectedly, the FgMyo1-actin cytoskeleton is not involved in biosynthesis of another secondary metabolite tested. Taken together, this study uncovers a novel function of myosin I in regulating mycotoxin biosynthesis in filamentous fungi.

The fungal myosin I is essential for Fusarium toxisome formation.

Science.gov (United States)

Tang, Guangfei; Chen, Yun; Xu, Jin-Rong; Kistler, H Corby; Ma, Zhonghua

2018-01-01

Myosin-I molecular motors are proposed to function as linkers between membranes and the actin cytoskeleton in several cellular processes, but their role in the biosynthesis of fungal secondary metabolites remain elusive. Here, we found that the myosin I of Fusarium graminearum (FgMyo1), the causal agent of Fusarium head blight, plays critical roles in mycotoxin biosynthesis. Inhibition of myosin I by the small molecule phenamacril leads to marked reduction in deoxynivalenol (DON) biosynthesis. FgMyo1 also governs translation of the DON biosynthetic enzyme Tri1 by interacting with the ribosome-associated protein FgAsc1. Disruption of the ATPase activity of FgMyo1 either by the mutation E420K, down-regulation of FgMyo1 expression or deletion of FgAsc1 results in reduced Tri1 translation. The DON biosynthetic enzymes Tri1 and Tri4 are mainly localized to subcellular structures known as toxisomes in response to mycotoxin induction and the FgMyo1-interacting protein, actin, participates in toxisome formation. The actin polymerization disruptor latrunculin A inhibits toxisome assembly. Consistent with this observation, deletion of the actin-associated proteins FgPrk1 and FgEnd3 also results in reduced toxisome formation. Unexpectedly, the FgMyo1-actin cytoskeleton is not involved in biosynthesis of another secondary metabolite tested. Taken together, this study uncovers a novel function of myosin I in regulating mycotoxin biosynthesis in filamentous fungi.

Energy efficiency: Lever for the Energy Transition

International Nuclear Information System (INIS)

2012-12-01

The Eco-electric industry group (FFIE, FGME, Gimelec, IGNES, SERCE) has conducted a study to evaluate the energy saving potential of active energy efficiency solutions in the residential and commercial building sectors. Based on field implementations and demonstrators, it has been demonstrated that active energy efficiency can sustainably achieve substantial savings for households, companies and public authorities. Energy Efficiency - Lever for the energy transition presents the results and conclusions of that study, alongside with recommendations for public authority in terms of building retrofit policy for putting France on the best possible 'trajectory' from a budgetary and environmental point of view. (author)

Phosphorylated peptides occur in a non-helical portion of the tail of a catch muscle myosin

International Nuclear Information System (INIS)

Castellani, L.; Elliott, B.W. Jr.; Cohen, C.

1987-01-01

Myosin from a molluscan catch muscle (the Anterior Byssus Retractor (ABRM) of Mytilus edulis) is unusual in being phosphorylated in the rod by an endogenous heavy-chain kinase. This phosphorylation enhances myosin solubility at low ionic strength and induces molecular folding of the myosin tail. Papain and chymotryptic cleavage of this myosin, phosphorylated with [γ- 32 P]ATP, indicates that the phosphorylated residues are associated with the carboxy-terminal end of the light meromyosin. Ion-exchange and reverse-phase HPLC of radiolabeled chymotryptic peptides allow the isolation of two different peptides with high specific activity. One of these peptides is rich in lysine and arginine residues, a finding consistent with the observation that basic residues often determine the substrate specificity of protein kinases. The second peptide contains proline residues. Taken together, these results suggest that, as in the case of Acanthamoeba myosin, phosphorylation occurs in a nonhelical portion of the rod that may also control solubility. Identification of the residues that are phosphorylated and their location in the rod may reveal how the phosphorylation-dependent changes observed in the myosin in vitro are related to changes in intermolecular interactions in the thick filaments in vivo

The Effect of Experimental Hyperthyroidism on Characteristics of Actin-Myosin Interaction in Fast and Slow Skeletal Muscles.

Science.gov (United States)

Kopylova, G V; Shchepkin, D V; Bershitsky, S Y

2018-05-01

The molecular mechanism of the failure of contractile function of skeletal muscles caused by oxidative damage to myosin in hyperthyroidism is not fully understood. Using an in vitro motility assay, we studied the effect of myosin damage caused by oxidative stress in experimental hyperthyroidism on the actin-myosin interaction and its regulation by calcium. We found that hyperthyroidism-induced oxidation of myosin is accompanied by a decrease in the sliding velocity of the regulated thin filaments in the in vitro motility assay, and this effect is increased with the duration of the pathological process.

Commissioner for Inland Revenue v Lever Brothers and Unilever Ltd

African Journals Online (AJOL)

kirstam

21Key words: Lever Brothers and Unilever; South African income tax; source of income; interest; the “practical man”; the .... facilities, and he housed his employees in a model village of well-built homes on the factory site. ... be cancelled and any excess of the value of the shares over the debt would be adjusted by a money.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

NARCIS (Netherlands)

Homburger, J.R. (Julian R.); Green, E.M. (Eric M.); Caleshu, C. (Colleen); Sunitha, M.S. (Margaret S.); Taylor, R.E. (Rebecca E.); Ruppel, K.M. (Kathleen M.); Metpally, R.P.R. (Raghu Prasad Rao); S.D. Colan (Steven); M. Michels (Michelle); Day, S.M. (Sharlene M.); I. Olivotto (Iacopo); Bustamante, C.D. (Carlos D.); Dewey, F.E. (Frederick E.); Ho, C.Y. (Carolyn Y.); Spudich, J.A. (James A.); Ashley, E.A. (Euan A.)

2016-01-01

textabstractMyosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac

Myosin isoform determines the conformational dynamics and cooperativity of actin filaments in the strongly bound actomyosin complex

Science.gov (United States)

Prochniewicz, Ewa; Chin, Harvey F.; Henn, Arnon; Hannemann, Diane E.; Olivares, Adrian O.; Thomas, David D.; De La Cruz, Enrique M.

2010-01-01

SUMMARY We have used transient phosphorescence anisotropy (TPA) to detect the microsecond rotational dynamics of erythrosin iodoacetamide (ErIA)-labeled actin strongly bound to single-headed fragments of muscle myosin (muscle S1) and non-muscle myosin V (MV). The conformational dynamics of actin filaments in solution are markedly influenced by the isoform of bound myosin. Both myosins increase the final anisotropy of actin at sub-stoichiometric binding densities, indicating long-range, non-nearest neighbor cooperative restriction of filament rotational dynamics amplitude, but the cooperative unit is larger with MV than muscle S1. Both myosin isoforms also cooperatively affect the actin filament rotational correlation time, but with opposite effects; muscle S1 decreases rates of intrafilament torsional motion, while binding of MV increases the rates of motion. The cooperative effects on the rates of intrafilament motions correlate with the kinetics of myosin binding to actin filaments such that MV binds more rapidly, and muscle myosin more slowly, to partially decorated filaments than to bare filaments. The two isoforms also differ in their effects on the phosphorescence lifetime of the actin-bound ErIA; while muscle S1 increases the lifetime, suggesting decreased aqueous exposure of the probe, MV does not induce a significant change. We conclude that the dynamics and structure of actin in the strongly bound actomyosin complex is determined by the isoform of the bound myosin, in a manner likely to accommodate the diverse functional roles of actomyosin in muscle and non-muscle cells. PMID:19962990

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Science.gov (United States)

Venit, Tomáš; Dzijak, Rastislav; Kalendová, Alžběta; Kahle, Michal; Rohožková, Jana; Schmidt, Volker; Rülicke, Thomas; Rathkolb, Birgit; Hans, Wolfgang; Bohla, Alexander; Eickelberg, Oliver; Stoeger, Tobias; Wolf, Eckhard; Yildirim, Ali Önder; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Hozák, Pavel

2013-01-01

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes.

A novel role for myosin II in insulin-stimulated glucose uptake in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Steimle, Paul A.; Kent Fulcher, F.; Patel, Yashomati M.

2005-01-01

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles from an intracellular pool to the plasma membrane. The studies presented here show that inhibition of myosin II activity impairs GLUT4-mediated glucose uptake but not GLUT4 translocation to the plasma membrane. We also show that adipocytes express both myosin IIA and IIB isoforms, and that myosin IIA is recruited to the plasma membrane upon insulin stimulation. Taken together, the data presented here represent the first demonstration that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. Based on our findings, we hypothesize that myosin II is activated upon insulin stimulation and recruited to the cell cortex to facilitate GLUT4 fusion with the plasma membrane. The identification of myosin II as a key component of GLUT4-mediated glucose uptake represents an important advance in our understanding of the mechanisms regulating glucose homeostasis

Myosin-II sets the optimal response time scale of chemotactic amoeba

Science.gov (United States)

Hsu, Hsin-Fang; Westendorf, Christian; Tarantola, Marco; Bodenschatz, Eberhard; Beta, Carsten

2014-03-01

The response dynamics of the actin cytoskeleton to external chemical stimuli plays a fundamental role in numerous cellular functions. One of the key players that governs the dynamics of the actin network is the motor protein myosin-II. Here we investigate the role of myosin-II in the response of the actin system to external stimuli. We used a microfluidic device in combination with a photoactivatable chemoattractant to apply stimuli to individual cells with high temporal resolution. We directly compare the actin dynamics in Dictyostelium discodelium wild type (WT) cells to a knockout mutant that is deficient in myosin-II (MNL). Similar to the WT a small population of MNL cells showed self-sustained oscillations even in absence of external stimuli. The actin response of MNL cells to a short pulse of chemoattractant resembles WT during the first 15 sec but is significantly delayed afterward. The amplitude of the dominant peak in the power spectrum from the response time series of MNL cells to periodic stimuli with varying period showed a clear resonance peak at a forcing period of 36 sec, which is significantly delayed as compared to the resonance at 20 sec found for the WT. This shift indicates an important role of myosin-II in setting the response time scale of motile amoeba. Institute of Physics und Astronomy, University of Potsdam, Karl-Liebknecht-Str. 24/25, 14476 Potsdam, Germany.

Task oriented evaluation system for maintenance robots

International Nuclear Information System (INIS)

Asame, Hajime; Endo, Isao; Kotosaka, Shin-ya; Takata, Shozo; Hiraoka, Hiroyuki; Kohda, Takehisa; Matsumoto, Akihiro; Yamagishi, Kiichiro.

1994-01-01

The adaptability evaluation of maintenance robots to autonomous plants has been discussed. In this paper, a new concept of autonomous plant with maintenance robots are introduced, and a framework of autonomous maintenance system is proposed. Then, task-oriented evaluation of robot arms is discussed for evaluating their adaptability to maintenance tasks, and a new criterion called operability is proposed for adaptability evaluation. The task-oriented evaluation system is implemented and applied to structural design of robot arms. Using genetic algorithm, an optimal structure adaptable to a pump disassembly task is obtained. (author)

Engineering Circular Gliding of Actin Filaments Along Myosin-Patterned DNA Nanotube Rings To Study Long-Term Actin-Myosin Behaviors.

Science.gov (United States)

Hariadi, Rizal F; Appukutty, Abhinav J; Sivaramakrishnan, Sivaraj

2016-09-27

Nature has evolved molecular motors that are critical in cellular processes occurring over broad time scales, ranging from seconds to years. Despite the importance of the long-term behavior of molecular machines, topics such as enzymatic lifetime are underexplored due to the lack of a suitable approach for monitoring motor activity over long time periods. Here, we developed an "O"-shaped Myosin Empowered Gliding Assay (OMEGA) that utilizes engineered micron-scale DNA nanotube rings with precise arrangements of myosin VI to trap gliding actin filaments. This circular gliding assay platform allows the same individual actin filament to glide over the same myosin ensemble (50-1000 motors per ring) multiple times. First, we systematically characterized the formation of DNA nanotubes rings with 4, 6, 8, and 10 helix circumferences. Individual actin filaments glide along the nanotube rings with high processivity for up to 12.8 revolutions or 11 min in run time. We then show actin gliding speed is robust to variation in motor number and independent of ring curvature within our sample space (ring diameter of 0.5-4 μm). As a model application of OMEGA, we then analyze motor-based mechanical influence on "stop-and-go" gliding behavior of actin filaments, revealing that the stop-to-go transition probability is dependent on motor flexibility. Our circular gliding assay may provide a closed-loop platform for monitoring long-term behavior of broad classes of molecular motors and enable characterization of motor robustness and long time scale nanomechanical processes.

Method and system for dual resolution translation stage

Science.gov (United States)

Halpin, John Michael

2014-04-22

A dual resolution translation stage includes a stage assembly operable to receive an optical element and a low resolution adjustment device mechanically coupled to the stage assembly. The dual resolution stage also includes an adjustable pivot block mechanically coupled to the stage assembly. The adjustable pivot block includes a pivot shaft. The dual resolution stage further includes a lever arm mechanically coupled to the adjustable pivot block. The lever arm is operable to pivot about the pivot shaft. The dual resolution stage additionally includes a high resolution adjustment device mechanically coupled to the lever arm and the stage assembly.

Arm coordination in octopus crawling involves unique motor control strategies.

Science.gov (United States)

Levy, Guy; Flash, Tamar; Hochner, Binyamin

2015-05-04

To cope with the exceptional computational complexity that is involved in the control of its hyper-redundant arms [1], the octopus has adopted unique motor control strategies in which the central brain activates rather autonomous motor programs in the elaborated peripheral nervous system of the arms [2, 3]. How octopuses coordinate their eight long and flexible arms in locomotion is still unknown. Here, we present the first detailed kinematic analysis of octopus arm coordination in crawling. The results are surprising in several respects: (1) despite its bilaterally symmetrical body, the octopus can crawl in any direction relative to its body orientation; (2) body and crawling orientation are monotonically and independently controlled; and (3) contrasting known animal locomotion, octopus crawling lacks any apparent rhythmical patterns in limb coordination, suggesting a unique non-rhythmical output of the octopus central controller. We show that this uncommon maneuverability is derived from the radial symmetry of the arms around the body and the simple pushing-by-elongation mechanism by which the arms create the crawling thrust. These two together enable a mechanism whereby the central controller chooses in a moment-to-moment fashion which arms to recruit for pushing the body in an instantaneous direction. Our findings suggest that the soft molluscan body has affected in an embodied way [4, 5] the emergence of the adaptive motor behavior of the octopus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inverse kinematics of OWI-535 robotic arm

OpenAIRE

DEBENEC, PRIMOŽ

2015-01-01

The thesis aims to calculate the inverse kinematics for the OWI-535 robotic arm. The calculation of the inverse kinematics determines the joint parameters that provide the right pose of the end effector. The pose consists of the position and orientation, however, we will focus only on the second one. Due to arm limitations, we have created our own type of the calculation of the inverse kinematics. At first we have derived it only theoretically, and then we have transferred the derivation into...

New approaches to high-throughput structure characterization of SH3 complexes: the example of Myosin-3 and Myosin-5 SH3 domains from S. cerevisiae.

Science.gov (United States)

Musi, Valeria; Birdsall, Berry; Fernandez-Ballester, Gregorio; Guerrini, Remo; Salvatori, Severo; Serrano, Luis; Pastore, Annalisa

2006-04-01

SH3 domains are small protein modules that are involved in protein-protein interactions in several essential metabolic pathways. The availability of the complete genome and the limited number of clearly identifiable SH3 domains make the yeast Saccharomyces cerevisae an ideal proteomic-based model system to investigate the structural rules dictating the SH3-mediated protein interactions and to develop new tools to assist these studies. In the present work, we have determined the solution structure of the SH3 domain from Myo3 and modeled by homology that of the highly homologous Myo5, two myosins implicated in actin polymerization. We have then implemented an integrated approach that makes use of experimental and computational methods to characterize their binding properties. While accommodating their targets in the classical groove, the two domains have selectivity in both orientation and sequence specificity of the target peptides. From our study, we propose a consensus sequence that may provide a useful guideline to identify new natural partners and suggest a strategy of more general applicability that may be of use in other structural proteomic studies.

Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

Directory of Open Access Journals (Sweden)

Mohanan Valiya Veettil

2010-12-01

Full Text Available KSHV is etiologically associated with Kaposi's sarcoma (KS, an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA, in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex

Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

Directory of Open Access Journals (Sweden)

Ivanna Ihnatovych

Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

Creativity and Control : A Paradox-Evidence from the Levers of Control Framework

NARCIS (Netherlands)

Speklé, R.F.; van Elten, Hilco; Widener, Sally

2017-01-01

Both control and creativity are important drivers of organizational success (Gilson, Mathieu, Shally, and Ruddy 2005; Hirst, Van Knippenberg, Chen, and Sacramento 2011). However, they are often regarded as conflicting. We use the Levers of Control (LoC) framework to examine the relationships between

Creativity and Control : A Paradox: Evidence from the Levers of Control Framework

NARCIS (Netherlands)

Speklé, R.F.; Elten, van H.J.; Widener, S.

2017-01-01

Both control and creativity are important drivers of organizational success (Gilson, Mathieu, Shally, and Ruddy 2005; Hirst, Van Knippenberg, Chen, and Sacramento 2011). However, they are often regarded as conflicting. We use the Levers of Control (LoC) framework to examine the relationships between

Myosin isoform switching during assembly of the Drosophila flight muscle thick filament lattice.

Science.gov (United States)

Orfanos, Zacharias; Sparrow, John C

2013-01-01

During muscle development myosin molecules form symmetrical thick filaments, which integrate with the thin filaments to produce the regular sarcomeric lattice. In Drosophila indirect flight muscles (IFMs) the details of this process can be studied using genetic approaches. The weeP26 transgenic line has a GFP-encoding exon inserted into the single Drosophila muscle myosin heavy chain gene, Mhc. The weeP26 IFM sarcomeres have a unique MHC-GFP-labelling pattern restricted to the sarcomere core, explained by non-translation of the GFP exon following alternative splicing. Characterisation of wild-type IFM MHC mRNA confirmed the presence of an alternately spliced isoform, expressed earlier than the major IFM-specific isoform. The two wild-type IFM-specific MHC isoforms differ by the presence of a C-terminal 'tailpiece' in the minor isoform. The sequential expression and assembly of these two MHCs into developing thick filaments suggest a role for the tailpiece in initiating A-band formation. The restriction of the MHC-GFP sarcomeric pattern in weeP26 is lifted when the IFM lack the IFM-specific myosin binding protein flightin, suggesting that it limits myosin dissociation from thick filaments. Studies of flightin binding to developing thick filaments reveal a progressive binding at the growing thick filament tips and in a retrograde direction to earlier assembled, proximal filament regions. We propose that this flightin binding restricts myosin molecule incorporation/dissociation during thick filament assembly and explains the location of the early MHC isoform pattern in the IFM A-band.

Reliable quantification of bite-force performance requires use of appropriate biting substrate and standardization of bite out-lever.

Science.gov (United States)

Lappin, A Kristopher; Jones, Marc E H

2014-12-15

Bite-force performance is an ecologically important measure of whole-organism performance that shapes dietary breadth and feeding strategies and, in some taxa, determines reproductive success. It also is a metric that is crucial to testing and evaluating biomechanical models. We reviewed nearly 100 published studies of a range of taxa that incorporate direct in vivo measurements of bite force. Problematically, methods of data collection and processing vary considerably among studies. In particular, there is little consensus on the appropriate substrate to use on the biting surface of force transducers. In addition, the bite out-lever, defined as the distance from the fulcrum (i.e. jaw joint) to the position along the jawline at which the jaws engage the transducer, is rarely taken into account. We examined the effect of bite substrate and bite out-lever on bite-force estimates in a diverse sample of lizards. Results indicate that both variables have a significant impact on the accuracy of measurements. Maximum bite force is significantly greater using leather as the biting substrate compared with a metal substrate. Less-forceful bites on metal are likely due to inhibitory feedback from mechanoreceptors that prevent damage to the feeding apparatus. Standardization of bite out-lever affected which trial produced maximum performance for a given individual. Indeed, maximum bite force is usually underestimated without standardization because it is expected to be greatest at the minimum out-lever (i.e. back of the jaws), which in studies is rarely targeted with success. We assert that future studies should use a pliable substrate, such as leather, and use appropriate standardization for bite out-lever. © 2014. Published by The Company of Biologists Ltd.

Formation of contractile networks and fibers in the medial cell cortex through myosin-II turnover, contraction, and stress-stabilization.

Science.gov (United States)

Nie, Wei; Wei, Ming-Tzo; Ou-Yang, H Daniel; Jedlicka, Sabrina S; Vavylonis, Dimitrios

2015-01-01

The morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked fibers along the contacting surface. The motor activity and minifilament assembly of non-muscle myosin-II is an important component of cortical cytoskeletal remodeling during mechanosensing. We used experiments and computational modeling to study cortical myosin-II dynamics in adhered cells. Confocal microscopy was used to image the medial cell cortex of HeLa cells stably expressing myosin regulatory light chain tagged with GFP (MRLC-GFP). The distribution of MRLC-GFP fibers and focal adhesions was classified into three types of network morphologies. Time-lapse movies show: myosin foci appearance and disappearance; aligning and contraction; stabilization upon alignment. Addition of blebbistatin, which perturbs myosin motor activity, leads to a reorganization of the cortical networks and to a reduction of contractile motions. We quantified the kinetics of contraction, disassembly and reassembly of myosin networks using spatio-temporal image correlation spectroscopy (STICS). Coarse-grained numerical simulations include bipolar minifilaments that contract and align through specified interactions as basic elements. After assuming that minifilament turnover decreases with increasing contractile stress, the simulations reproduce stress-dependent fiber formation in between focal adhesions above a threshold myosin concentration. The STICS correlation function in simulations matches the function measured in experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. © 2015 Wiley Periodicals, Inc.

Characterizing piezoscanner hysteresis and creep using optical levers and a reference nanopositioning stage

International Nuclear Information System (INIS)

Xie, H.; Regnier, S.; Rakotondrabe, M.

2009-01-01

A method using atomic force microscope (AFM) optical levers and a reference nanopositioning stage has been developed to characterize piezoscanner hysteresis and creep. The piezoscanner is fixed on a closed-loop nanopositioning stage, both of which have the same arrangement on each axis of the three spatial directions inside the AFM-based nanomanipulation system. In order to achieve characterization, the optical lever is used as a displacement sensor to measure the relative movement between the nanopositioning stage and the piezoscanner by lateral tracking a well-defined slope with the tapping mode of the AFM cantilever. This setup can be used to estimate a piezoscanner's voltage input with a reference displacement from the nanopositioning stage. The hysteresis and creep were accurately calibrated by the method presented, which use the current setup of the AFM-based nanomanipulation system without any modification or additional devices.

Concise and diversity-oriented synthesis of ligand arm-functionalized azoamides.

Science.gov (United States)

Urankar, Damijana; Kosmrlj, Janez

2008-01-01

Azoamides, previously established as bioactive intracellular GSH-depleting agents, were decorated with a terminal alkyne moiety to 4 and then were transformed, by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), into different ligand-arm functionalized azoamides 6. Azides 5 having ligand-arms amenable for binding to platinum(II) were selected for this study. Because, for the fragile azoamides 4, the typically employed reaction conditions for CuAAC failed, several alternative solvents and copper catalysts were tested. Excellent results were obtained with copper(II) sulfate pentahydrate/metallic copper and especially with heterogeneous catalysts, such as copper-in-charcoal, cupric oxide, and cuprous oxide. The heterogeneous catalysts were employed to obtain the desired products in almost quantitative yields by a simple three-step "stir-filter-evaporate" protocol with no or negligible contamination with copper impurities. This is of particular importance because compounds 6 have been designed for coordination.

Evolutionary Trends in the Jaw Adductor Mechanics of Ornithischian Dinosaurs.

Science.gov (United States)

Nabavizadeh, Ali

2016-03-01

Jaw mechanics in ornithischian dinosaurs have been widely studied for well over a century. Most of these studies, however, use only one or few taxa within a given ornithischian clade as a model for feeding mechanics across the entire clade. In this study, mandibular mechanical advantages among 52 ornithischian genera spanning all subclades are calculated using 2D lever arm methods. These lever arm calculations estimate the effect of jaw shape and difference in adductor muscle line of action on relative bite forces along the jaw. Results show major instances of overlap between taxa in tooth positions at which there was highest mechanical advantage. A relatively low bite force is seen across the tooth row among thyreophorans (e.g., stegosaurs and ankylosaurs), with variation among taxa. A convergent transition occurs from a more evenly distributed bite force along the jaw in basal ornithopods and basal marginocephalians to a strong distal bite force in hadrosaurids and ceratopsids, respectively. Accordingly, adductor muscle vector angles show repeated trends from a mid-range caudodorsal orientation in basal ornithischians to a decrease in vector angles indicating more caudally oriented jaw movements in derived taxa (e.g., derived thyreophorans, basal ornithopods, lambeosaurines, pachycephalosaurs, and derived ceratopsids). Analyses of hypothetical jaw morphologies were also performed, indicating that both the coronoid process and lowered jaw joint increase moment arm length therefore increasing mechanical advantage of the jaw apparatus. Adaptive trends in craniomandibular anatomy show that ornithischians evolved more complex feeding apparatuses within different clades as well as morphological convergences between clades. © 2016 Wiley Periodicals, Inc.

Great expectations: patient choice as a lever for change in health care.

NARCIS (Netherlands)

Friele, R.D.

2011-01-01

The introduction of market forces in the Dutch health care system is partially based on assumptions regarding patients' behavior. They are expected to actively choose their care providers. Their choices may work as a lever for change. When asked, most patients say that they find it very important to

Posture of the arm when grasping spheres to place them elsewhere

NARCIS (Netherlands)

Schot, W.D.; Brenner, E.; Smeets, J.B.J.

2010-01-01

Despite the infinitely many ways to grasp a spherical object, regularities have been observed in the posture of the arm and the grasp orientation. In the present study, we set out to determine the factors that predict the grasp orientation and the final joint angles of reach-tograsp movements.

Phosphorylation of Tropomyosin Extends Cooperative Binding of Myosin Beyond a Single Regulatory Unit

OpenAIRE

Rao, Vijay S.; Marongelli, Ellisha N.; Guilford, William H.

2009-01-01

Tropomyosin (Tm) is one of the major phosphoproteins comprising the thin filament of muscle. However, the specific role of Tm phosphorylation in modulating the mechanics of actomyosin interaction has not been determined. Here we show that Tm phosphorylation is necessary for long-range cooperative activation of myosin binding. We used a novel optical trapping assay to measure the isometric stall force of an ensemble of myosin molecules moving actin filaments reconstituted with either natively ...

BMP-2 Overexpression Augments Vascular Smooth Muscle Cell Motility by Upregulating Myosin Va via Erk Signaling

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Ming Zhang

2014-01-01

Full Text Available Background. The disruption of physiologic vascular smooth muscle cell (VSMC migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. Methods. VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2. Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca2+ oscillations were recorded. Results. VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca2+ oscillations, generated largely by a “cytosolic oscillator”. Conclusion. BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca2+ oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.

Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

Science.gov (United States)

Warren, Sonisha A; Briggs, Laura E; Zeng, Huadong; Chuang, Joyce; Chang, Eileen I; Terada, Ryota; Li, Moyi; Swanson, Maurice S; Lecker, Stewart H; Willis, Monte S; Spinale, Francis G; Maupin-Furlowe, Julie; McMullen, Julie R; Moss, Richard L; Kasahara, Hideko

2012-11-27

Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems. Our results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.

In Silico Study of Spacer Arm Length Influence on Drug Vectorization by Fullerene C60

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Haifa Khemir

2015-01-01

Full Text Available This work studies theoretically the effect of spacer arm lengths on the characteristics of a fullerene C60-based nanovector. The spacer arm is constituted of a carbon chain including a variable number of methylene groups (n = 2–11. To improve the ability of the fullerene carriage, two arms are presented simultaneously through a malonyl bridge. Then the evolution of selected physicochemical parameters is monitored as a function of the spacer arm length and the angle between the two arms. We show here that while the studied characteristics are almost independent of the spacer arm length or vary monotonically with it, the dipole moment and its orientation vary periodically with the parity of the number of carbon atoms. This periodicity is related to both modules and orientations of dipole moments of the spacer arms. In the field of chemical synthesis, these results highlight the importance of theoretical calculations for the optimization of operating conditions. In the field of drug discovery, they show that theoretical calculations of the chemical properties of a drug candidate can help predict its in vivo behaviour, notably its bioavailability and biodistribution, which are known to be tightly dependent of its polarity.

Myosin XI-dependent formation of tubular structures from endoplasmic reticulum isolated from tobacco cultured BY-2 cells.

Science.gov (United States)

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-05-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER.

Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Chung, Le Thi Kim; Hosaka, Toshio; Harada, Nagakatsu; Jambaldorj, Bayasgalan; Fukunaga, Keiko; Nishiwaki, Yuka; Teshigawara, Kiyoshi; Sakai, Tohru; Nakaya, Yutaka; Funaki, Makoto

2010-01-01

In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4 to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.

RANGE OF MOTION EXERCISE OF ARMS INCREASES THE MUCLE STRENGTH FOR POST STROKE PATIENTS

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Judi Nurbaeni

2017-04-01

Full Text Available Introduction: Someone attached by stroke can’t do their activity fluently because stroke can cause the weakness of motor and sensor function. This condition cause physical defect and give effect in social and economic too, because someone who suffered stroke usually still in productive age. The objective of this study was to examine the effect of arm range of motion in the muscle strength of post stroke patient. Method: Pre experimental pre–post test design was used in this study. Population of this study was post stroke patient in Wijayakusuma ward dr. Soedono Hospital and total samples were 11 respondents. Independent variable was arm range of motion exercise, dependent variable was strength of arm muscle. Data were collected by observation with manual muscle testing of Lovelt, Naniel and Worthinghom and then analyzed using wilcoxon signed rank test with signi fi cant level of α ≤ 0.05. Result: The result showed that 11 respondents had increased their strength of muscle (p = 0.04. Discussion: It can be concluded that the strength of muscle increased after get arm range of motion exercise. When range of motion had been done Ca+ will be activated by cell so that happen integrity of muscle protein. If Ca+ and troponin had been activated, actin and myosin would have been defensed, so that can moved the skeletal and followed by muscle contraction, expand, outgrow and had a tonus. This condition can showed the strength of muscle.

Measurements of the LHCb software stack on the ARM architecture

International Nuclear Information System (INIS)

Kartik, S Vijay; Couturier, Ben; Clemencic, Marco; Neufeld, Niko

2014-01-01

The ARM architecture is a power-efficient design that is used in most processors in mobile devices all around the world today since they provide reasonable compute performance per watt. The current LHCb software stack is designed (and thus expected) to build and run on machines with the x86/x86 6 4 architecture. This paper outlines the process of measuring the performance of the LHCb software stack on the ARM architecture – specifically, the ARMv7 architecture on Cortex-A9 processors from NVIDIA and on full-fledged ARM servers with chipsets from Calxeda – and makes comparisons with the performance on x86 6 4 architectures on the Intel Xeon L5520/X5650 and AMD Opteron 6272. The paper emphasises the aspects of performance per core with respect to the power drawn by the compute nodes for the given performance – this ensures a fair real-world comparison with much more 'powerful' Intel/AMD processors. The comparisons of these real workloads in the context of LHCb are also complemented with the standard synthetic benchmarks HEPSPEC and Coremark. The pitfalls and solutions for the non-trivial task of porting the source code to build for the ARMv7 instruction set are presented. The specific changes in the build process needed for ARM-specific portions of the software stack are described, to serve as pointers for further attempts taken up by other groups in this direction. Cases where architecture-specific tweaks at the assembler lever (both in ROOT and the LHCb software stack) were needed for a successful compile are detailed – these cases are good indicators of where/how the software stack as well as the build system can be made more portable and multi-arch friendly. The experience gained from the tasks described in this paper are intended to i) assist in making an informed choice about ARM-based server solutions as a feasible low-power alternative to the current compute nodes, and ii) revisit the software design and build system for portability and

Implementing a university e-learning strategy: levers for change within academic schools

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Rhona Sharpe

2006-12-01

Full Text Available This paper describes the implementation of an e-learning strategy at a single higher education institution in terms of the levers used to promote effective uptake and ensure sustainable embedding. The focus of this work was at the level of the academic school using a range of change practices including the appointment of school-based learning technologists and e-learning champions, supporting schools to write their own strategies, a pedagogical framework of engaging with e-learning, and curriculum development and evaluation of school-supported projects. It is clear that the implementation of the e-learning strategy has led to a large and increasing proportion of our students experiencing blended learning. In addition, there are initial indications that this has enhanced some learning and teaching processes. Where there has been sustainable embedding of effective e-learning, the following levers were identified as particularly important: flexibility in practices that allow schools to contextualise their plans for change, the facilitation of communities of key staff and creating opportunities for staff to voice and challenge their beliefs about e-learning.

The local expression of adult chicken heart myosins during development. I. The three days embryonic chicken heart

NARCIS (Netherlands)

Sanders, E.; Moorman, A. F.; Los, J. A.

1984-01-01

Immunofluorescence studies were performed on serial sections of three days embryonic chicken hearts using antibodies specific for adult atrial and ventricular myosin heavy chains respectively. The anti-ventricular myosin serum reacted with the entire myocardium showing a decreasing intensity going

CALIX[4]ARENE C-99 INHIBITS MYOSIN ATPase ACTIVITY AND CHANGES THE ORGANIZATION OF CONTRACTILE FILAMENTS OF MYOMETRIUM.

Science.gov (United States)

Labyntseva, R D; Bevza, A A; Lul'ko, A O; Cherenok, S O; Kalchenko, V I; Kosterin, S O

2015-01-01

Calix[4]arenes are cup-like macrocyclic (polyphenolic) compounds, they are regarded as promising molecular "platforms" for the design of new physiologically active compounds. We have earlier found that calix[4]arene C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus in vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes. It was found that the ATPase activity of myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was almost 50% lower than in control. Additionally, we have revealed the effect of calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus myocytes by the method of confocal microscopy. This effect can be caused by reorganization of the structure of the contractile smooth muscle cell proteins due to their interaction with calix[4]arene. The obtained results demonstrate the ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and affect not only the myosin ATPase activity, but also the structure of the actin and myosin filaments in the myometrial cells. Demonstrated ability of calix[4]arene C-99 can be used for development of new pharmacological agents for efficient normalization of myometrial contractile hyperfunction.

Calix[4]arene C-99 inhibits myosin ATPase activity and changes the organization of contractile filaments of myometrium

Directory of Open Access Journals (Sweden)

R. D. Labyntseva,

2015-12-01

Full Text Available Calix[4]arenes are cup-like macrocyclic (polyphenolic compounds, they are regarded as promising molecular “platforms” for the design of new physiologically active compounds. We have earlier found that сalix[4]arenе C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus іn vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes. It was found that the ATPase activity of myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was almost 50% lower than in control. Additionally, we have revealed the effect of calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus myocytes by the method of confocal microscopy. This effect can be caused by reorganization of the structure of the contractile smooth muscle cell proteins due to their interaction with calix[4]arene. The obtained results demonstrate the ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and affect not only the myosin ATPase activity, but also the structure of the actin and myosin filaments in the myometrial cells. Demonstrated ability of calix[4]arene C-99 can be used for development of new pharmacological agents for efficient normalization of myometrial contractile hyperfunction.

Clinical study on the time courses of serum myosin light chain I levels in patients with acute myocardial infarction

International Nuclear Information System (INIS)

Nakanishi, Masako; Saiki, Yasuhiko; Ui, Kazuyo

1992-01-01

Changes of serum myosin light chain I (Myosin LCI) concentrations and creatine kinase (CK) activities were serially measured in 23 patients with acute myocardial infarction. Intracoronary thrombolysis was performed in 14 patients (ICT group) while the remaining 9 patients were treated in the conventional manner (non ICT group). The relationships between the maximum levels of serum Myosin LCI or CK and a myocardial infarct size index or left ventricular function were evaluated in 18 patients. The myocardial infarct size index was determined by 201 Tl myocardial scintigrams performed in the chronic phase. Multiple peaks of Myosin LCI were observed in 64% (9/14) of the ICT group and the first peak in 6 of these patients appeared much earlier in the same time as CK peak than in the non-ICT group, while multiple peaks were seen only in one case in the non-ICT group. The infarct size index by 201 Tl myocardial SPECT correlated with maximum Myosin LCI levels (r=0.88, p<0.001, n=10) and CK activities (r=0.67, p<0.05, n=10). These results indicate that the measurement of serum Myosin LCI is very useful for estimating the extent of myocardial damage and suggest that myocardial degeneration occurs at a very early phase of myocardial infarction. (author)

Improper positioning of the elevator lever of duodenoscopes may lead to sequestered bacteria that survive disinfection by automated endoscope reprocessors.

Science.gov (United States)

Alfa, Michelle J; Singh, Harminder; Duerksen, Donald R; Schultz, Gale; Reidy, Carol; DeGagne, Pat; Olson, Nancy

2018-01-01

Some outbreaks associated with contaminated duodenoscopes have been attributed to biofilm formation. The objective of this study was to determine whether bacteria within an organic matrix could survive if the elevator lever was improperly positioned in the automated endoscope reprocessor (AER) after 1 round of reprocessing. Duodenoscope lever cavities with an open or sealed elevator wire channel were inoculated with 6-7 Log 10 of both Escherichia coli and Enterococcus faecalis in ATS2015 (Healthmark Industries, Fraser, MI) and dried for 2 hours. The duodenoscopes with the lever in the horizontal position were processed through 2 makes of AERs. The cavity was sampled using a flush-brush-flush method to determine the quantity of surviving bacteria. E faecalis (range, 21-6 Log 10 CFU) and E coli (range, 0-3 Log 10 CFU) survived disinfection of sealed or unsealed elevator wire channel duodenoscopes in 2 different AERs with and without cleaning cycles. If bacteria in organic residue are under the improperly positioned lever, then just 1 round of use is sufficient for bacteria to survive both liquid chemical sterilization and liquid chemical HLD regardless of whether or not the AER had a cleaning cycle. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Effect of cantilever geometry on the optical lever sensitivities and thermal noise method of the atomic force microscope.

Science.gov (United States)

Sader, John E; Lu, Jianing; Mulvaney, Paul

2014-11-01

Calibration of the optical lever sensitivities of atomic force microscope (AFM) cantilevers is especially important for determining the force in AFM measurements. These sensitivities depend critically on the cantilever mode used and are known to differ for static and dynamic measurements. Here, we calculate the ratio of the dynamic and static sensitivities for several common AFM cantilevers, whose shapes vary considerably, and experimentally verify these results. The dynamic-to-static optical lever sensitivity ratio is found to range from 1.09 to 1.41 for the cantilevers studied - in stark contrast to the constant value of 1.09 used widely in current calibration studies. This analysis shows that accuracy of the thermal noise method for the static spring constant is strongly dependent on cantilever geometry - neglect of these dynamic-to-static factors can induce errors exceeding 100%. We also discuss a simple experimental approach to non-invasively and simultaneously determine the dynamic and static spring constants and optical lever sensitivities of cantilevers of arbitrary shape, which is applicable to all AFM platforms that have the thermal noise method for spring constant calibration.

Drosophila UNC-45 prevents heat-induced aggregation of skeletal muscle myosin and facilitates refolding of citrate synthase

Energy Technology Data Exchange (ETDEWEB)

Melkani, Girish C.; Lee, Chi F.; Cammarato, Anthony [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States); Bernstein, Sanford I., E-mail: sbernst@sciences.sdsu.edu [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States)

2010-05-28

UNC-45 belongs to the UCS (UNC-45, CRO1, She4p) domain protein family, whose members interact with various classes of myosin. Here we provide structural and biochemical evidence that Escherichia coli-expressed Drosophila UNC-45 (DUNC-45) maintains the integrity of several substrates during heat-induced stress in vitro. DUNC-45 displays chaperone function in suppressing aggregation of the muscle myosin heavy meromyosin fragment, the myosin S-1 motor domain, {alpha}-lactalbumin and citrate synthase. Biochemical evidence is supported by electron microscopy, which reveals the first structural evidence that DUNC-45 prevents inter- or intra-molecular aggregates of skeletal muscle heavy meromyosin caused by elevated temperatures. We also demonstrate for the first time that UNC-45 is able to refold a denatured substrate, urea-unfolded citrate synthase. Overall, this in vitro study provides insight into the fate of muscle myosin under stress conditions and suggests that UNC-45 protects and maintains the contractile machinery during in vivo stress.

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

Science.gov (United States)

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

The Rho kinases I and II regulate different aspects of myosin II activity

DEFF Research Database (Denmark)

Yoneda, Atsuko; Multhaupt, Hinke A B; Couchman, John R

2005-01-01

The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. Both kinases are implicated in microfilament...... bundle assembly and smooth muscle contractility. Here, analysis of fibroblast adhesion to fibronectin revealed that although ROCK II was more abundant, its activity was always lower than ROCK I. Specific reduction of ROCK I by siRNA resulted in loss of stress fibers and focal adhesions, despite...

Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

Science.gov (United States)

Andruchov, Oleg; Galler, Stefan

2008-03-01

This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

Effects of BTS (N-benzyl-p-toluene sulphonamide), an inhibitor for myosin-actin interaction, on myofibrillogenesis in skeletal muscle cells in culture.

Science.gov (United States)

Kagawa, Maiko; Sato, Naruki; Obinata, Takashi

2006-11-01

Actin filaments align around myosin filaments in the correct polarity and in a hexagonal arrangement to form cross-striated structures. It has been postulated that this myosin-actin interaction is important in the initial phase of myofibrillogenesis. It was previously demonstrated that an inhibitor of actin-myosin interaction, BDM (2,3-butanedione monoxime), suppresses myofibril formation in muscle cells in culture. However, further study showed that BDM also exerts several additional effects on living cells. In this study, we further examined the role of actin-myosin interaction in myofibril assembly in primary cultures of chick embryonic skeletal muscle by applying a more specific inhibitor, BTS (N-benzyl-p-toluene sulphonamide), of myosin ATPase and actin-myosin interaction. The assembly of sarcomeric structures from myofibrillar proteins was examined by immunocytochemical methods with the application of BTS to myotubes just after fusion. Addition of BTS (10-50 microM) significantly suppressed the organization of actin and myosin into cross-striated structures. BTS also interfered in the organization of alpha-actinin, C-protein (or MyBP-C), and connectin (or titin) into ordered striated structures, though the sensitivity was less. Moreover, when myotubes cultured in the presence of BTS were transferred to a control medium, sarcomeric structures were formed in 2-3 days, indicating that the inhibitory effect of BTS on myotubes is reversible. These results show that actin-myosin interaction plays a critical role in the process of myofibrillogenesis.

Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction

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Nuno M. Coelho

2017-02-01

Full Text Available Discoidin domain receptor 1 (DDR1 is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA. Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen. Tractional remodeling of collagen was dependent on DDR1 clustering, activation, and interaction of the DDR1 C-terminal kinase domain with NMIIA filaments. Collagen remodeling by traction forces, DDR1 tyrosine phosphorylation, and myosin light chain phosphorylation were increased on stiff versus soft substrates. Thus, DDR1 clustering, activation, and interaction with NMIIA filaments enhance the collagen tractional remodeling that is important for collagen compaction in fibrosis.

Manual input device for controlling a robot arm

International Nuclear Information System (INIS)

Fischer, P.J.; Siva, K.V.

1990-01-01

A six-axis input device, eg joystick, is supported by a mechanism which enables the joystick to be aligned with any desired orientation, eg parallel to the tool. The mechanism can then be locked to provide a rigid support of the joystick. The mechanism may include three pivotal joints whose axes are perpendicular, each incorporating a clutch. The clutches may be electromagnetic or mechanical and may be operable jointly or independently. The robot arm comprises a base rotatable about a vertical axis, an upper arm, a forearm and a tool or grip rotatable about three perpendicular axes relative to the forearm. (author)

Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

Science.gov (United States)

Carew, Josephine A.; Goyal, Raj K.; Sullivan, Maryrose P.

2014-01-01

The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction. PMID:24516539

Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens shell on food-reinforced lever pressing by undeprived rats.

Science.gov (United States)

Stratford, Thomas R; Wirtshafter, David

2012-05-01

Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement. Copyright © 2012 Elsevier Inc. All rights reserved.

Orientation of axes in the elbow and forearm for biomechanical modelling

NARCIS (Netherlands)

Veeger, H. E J; Yu, B.

1996-01-01

To determine the three-dimensional positions and orientations of axes of rotation for elbow flexion and forearm prosupination, the flexion-extension and prosupination movements were measured for five arms. Four right and one arm were taken from four fresh cadavers. Movement was measured with a

Carboxyl-terminal-dependent recruitment of nonmuscle myosin II to megakaryocyte contractile ring during polyploidization.

Science.gov (United States)

Badirou, Idinath; Pan, Jiajia; Legrand, Céline; Wang, Aibing; Lordier, Larissa; Boukour, Siham; Roy, Anita; Vainchenker, William; Chang, Yunhua

2014-10-16

Endomitosis is a unique megakaryocyte (MK) differentiation process that is the consequence of a late cytokinesis failure associated with a contractile ring defect. Evidence from in vitro studies has revealed the distinct roles of 2 nonmuscle myosin IIs (NMIIs) on MK endomitosis: only NMII-B (MYH10), but not NMII-A (MYH9), is localized in the MK contractile ring and implicated in mitosis/endomitosis transition. Here, we studied 2 transgenic mouse models in which nonmuscle myosin heavy chain (NMHC) II-A was genetically replaced either by II-B or by a chimeric NMHCII that combined the head domain of II-A with the rod and tail domains of II-B. This study provides in vivo evidence on the specific role of NMII-B on MK polyploidization. It demonstrates that the carboxyl-terminal domain of the heavy chains determines myosin II localization to the MK contractile ring and is responsible for the specific role of NMII-B in MK polyploidization.

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

KAUST Repository

Conti, Antonio

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS\\'s pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V.

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

International Nuclear Information System (INIS)

Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C.

1990-01-01

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 ± 1.8 to 28.1 ± 6.8 (NS) at 3-day postirradiation, 37.7 ± 1.9 (P less than .001) at 6-day postirradiation, and 43.8 ± 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity

Coupling between myosin head conformation and the thick filament backbone structure.

Science.gov (United States)

Hu, Zhongjun; Taylor, Dianne W; Edwards, Robert J; Taylor, Kenneth A

2017-12-01

The recent high-resolution structure of the thick filament from Lethocerus asynchronous flight muscle shows aspects of thick filament structure never before revealed that may shed some light on how striated muscles function. The phenomenon of stretch activation underlies the function of asynchronous flight muscle. It is most highly developed in flight muscle, but is also observed in other striated muscles such as cardiac muscle. Although stretch activation is likely to be complex, involving more than a single structural aspect of striated muscle, the thick filament itself, would be a prime site for regulatory function because it must bear all of the tension produced by both its associated myosin motors and any externally applied force. Here we show the first structural evidence that the arrangement of myosin heads within the interacting heads motif is coupled to the structure of the thick filament backbone. We find that a change in helical angle of 0.16° disorders the blocked head preferentially within the Lethocerus interacting heads motif. This observation suggests a mechanism for how tension affects the dynamics of the myosin heads leading to a detailed hypothesis for stretch activation and shortening deactivation, in which the blocked head preferentially binds the thin filament followed by the free head when force production occurs. Copyright © 2017 Elsevier Inc. All rights reserved.

Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle

Science.gov (United States)

Boëda, Batiste; El-Amraoui, Aziz; Bahloul, Amel; Goodyear, Richard; Daviet, Laurent; Blanchard, Stéphane; Perfettini, Isabelle; Fath, Karl R.; Shorte, Spencer; Reiners, Jan; Houdusse, Anne; Legrain, Pierre; Wolfrum, Uwe; Richardson, Guy; Petit, Christine

2002-01-01

Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia. PMID:12485990

A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

Science.gov (United States)

Harper, David N; Langen, Anna-Lena; Schenk, Susan

2014-01-01

Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

Actin Filaments and Myosin I Alpha Cooperate with Microtubules for the Movement of LysosomesV⃞

OpenAIRE

Cordonnier, Marie-Neige; Dauzonne, Daniel; Louvard, Daniel; Coudrier, Evelyne

2001-01-01

An earlier report suggested that actin and myosin I alpha (MMIα), a myosin associated with endosomes and lysosomes, were involved in the delivery of internalized molecules to lysosomes. To determine whether actin and MMIα were involved in the movement of lysosomes, we analyzed by time-lapse video microscopy the dynamic of lysosomes in living mouse hepatoma cells (BWTG3 cells), producing green fluorescent protein actin or a nonfunctional domain of MMIα. In GFP-actin cells, lysosomes displayed ...

A comparative study of myosin and its subunits in adult and neonatal-rat hearts and in rat heart cells from young and old cultures.

OpenAIRE

Ghanbari, H A; McCarl, R L

1980-01-01

A possible explanation for the decrease in myosin Ca2+-dependent ATPase activity as rat heart cells age in culture is presented. The subunit structure and enzyme kinetics of myosin from adult and neonatal rat hearts and from rat heart cells of young and old cultures are compared. These studies indicate that the loss in Ca-ATPase activity of myosin from older cultures was an intrinsic property of the myosin itself. Myofibrillar fractions from the indicated four sources showed no qualitative or...

CONTRAST : gamification of arm-hand training for stroke survivors

NARCIS (Netherlands)

Jacobs, A.; Timmermans, A.A.A.; Michielsen, M.; Vander Plaetse, M.; Markopoulos, P.

2011-01-01

This paper describes the design of a serious game that supports arm-hand training for stroke survivors aiming to render rehabilitation training enjoyable and sustainable. The design of this game was based on combining well-known game-design principles and principles of task-oriented training. Most

Structural Studies of Three-Arm Star Block Copolymers Exposed to Extreme Stretch Suggests a Persistent Polymer Tube

Science.gov (United States)

Mortensen, Kell; Borger, Anine L.; Kirkensgaard, Jacob J. K.; Garvey, Christopher J.; Almdal, Kristoffer; Dorokhin, Andriy; Huang, Qian; Hassager, Ole

2018-05-01

We present structural small-angle neutron scattering studies of a three-armed polystyrene star polymer with short deuterated segments at the end of each arm. We show that the form factor of the three-armed star molecules in the relaxed state agrees with that of the random phase approximation of Gaussian chains. Upon exposure to large extensional flow conditions, the star polymers change conformation resulting in a highly stretched structure that mimics a fully extended three-armed tube model. All three arms are parallel to the flow, one arm being either in positive or negative stretching direction, while the two other arms are oriented parallel, right next to each other in the direction opposite to the first arm.

Individual differences in pavlovian autoshaping of lever pressing in rats predict stress-induced corticosterone release and mesolimbic levels of monoamines.

Science.gov (United States)

Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

2000-03-01

Pavlovian autoshaping CRs are directed and reflexive consummatory responses targeted at objects repeatedly paired with rewarding substances. To evaluate the hypothesis that autoshaping may provide an animal learning model of vulnerability to drug abuse, this study relates individual differences in lever-press autoshaping CR performance in rats to stress-induced corticosterone release and tissue monoamine levels in the mesolimbic dopamine tract. Long-Evans rats (n = 14) were given 20 sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of food US. Large between-subjects differences in lever-press autoshaping CR performance were observed, with group high CR frequency (n = 5) performing many more lever press CRs than group low CR frequency (n = 9). Tail-blood samples were obtained before and after the 20th autoshaping session, then 24 h later the rats were sacrificed and dissection yielded tissue samples of nucleus accumbens (NAC), prefrontal cortex (PFC), caudate putamen (CP), and ventral tegmental area (VTA). Serum levels of postsession corticosterone were elevated in group high CR frequency. HPLC revealed that group high CR frequency had higher tissue levels of dopamine and DOPAC in NAC, lower levels of DOPAC/DA turnover in CP, and lower levels of 5-HIAA and lower 5-HIAA/5-HT turnover in VTA. The neurochemical profile of rats that perform more autoshaping CRs share some features of vulnerability to drug abuse.

The fungal myosin I is essential for Fusarium toxisome formation

Science.gov (United States)

The mycotoxin deoxynivalenol (DON) is the most frequently detected secondary metabolite produced by Fusarium graminearum and other Fusarium spp. To date, relatively few studies have addressed how mycotoxin biosynthesis occurs in fungal cells. Here we found that myosin I governs translation of DON bi...

Influence of magnetic field on zebrafish activity and orientation in a plus maze.

Science.gov (United States)

Osipova, Elena A; Pavlova, Vera V; Nepomnyashchikh, Valentin A; Krylov, Viacheslav V

2016-01-01

We describe an impact of the geomagnetic field (GMF) and its modification on zebrafish's orientation and locomotor activity in a plus maze with four arms oriented to the north, east, south and west. Zebrafish's directional preferences were bimodal in GMF: they visited two arms oriented in opposed directions (east-west) most frequently. This bimodal preference remained stable for same individuals across experiments divided by several days. When the horizontal GMF component was turned 90° clockwise, the preference accordingly shifted by 90° to arms oriented to the north and south. Other modifications of GMF (reversal of both vertical and horizontal GMF components; reversal of vertical component only; and reversal of horizontal component only) did not exert any discernible effect on the orientation of zebrafish. The 90° turn of horizontal component also resulted in a significant increase of fish's locomotor activity in comparison with the natural GMF. This increase became even more pronounced when the horizontal component was repeatedly turned by 90° and back with 1min interval between turns. Our results show that GMF and its variations should be taken into account when interpreting zebrafish's directional preferences and locomotor activity in mazes and other experimental devices. Copyright © 2015. Published by Elsevier B.V.

Synthesis of total protein (TP) and myosin heavy chain (HC) isozymes in pressure overloaded rabbit hearts

International Nuclear Information System (INIS)

Nagai, R.; Martin, B.J.; Pritzl, N.; Zak, R.; Low, R.B.; Stirewalt, W.S.; Alpert, N.R.; Litten, R.Z.

1986-01-01

Pulmonary artery banding (PO) leads to a rapid increase in right ventricular (RV) weight as well as a shift toward β myosin isozyme. They determined: (1) the contributions of changes in the capacity (RNA content) and efficiency of total protein synthesis to the increase in RV weight; and (2) the relative contributions of translational and pretranslational mechanisms to the shift in myosin HC isotypes. The rates of synthesis in vivo of TP, α- and β-HC were measured by a constant infusion technique using 3 H-leucine. TP synthesis was 7 +/- 2(SD) mg/day in control (RV:367 +/- 70 mg) and was increased by 2.6 fold at day 2 and 2.9 fold at day 4 following PO (p < 0.01). RV RNA content was increased by 83% at day 2 and 103% at day 4 PO (p < 0.05). The efficiency of synthesis (rate/RNA) was also significantly higher at these time points (1.4- and 1.3-fold). β-HC synthesis was 0.6 +/- 0.2 mg/day in control and increased by 2.6 fold at day 2 and 3.5 fold at day 4 following PO. In contrast, the rate of synthesis of α-HC was unchanged. The relative rates of β-HC to total HC synthesis was correlated linearly with the relative levels of β-myosin mRNA as measured by S1 nuclease mapping. They conclude that increases in the proportion of β-HC myosin following PO is due to increases in the relative amount of β-myosin mRNA and therefore involves modulation of a pretranslational mechanism

Myosin XI-Dependent Formation of Tubular Structures from Endoplasmic Reticulum Isolated from Tobacco Cultured BY-2 Cells1[W][OA

Science.gov (United States)

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-01-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER. PMID:21427277

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients.

Science.gov (United States)

Conti, Antonio; Riva, Nilo; Pesca, Mariasabina; Iannaccone, Sandro; Cannistraci, Carlo V; Corbo, Massimo; Previtali, Stefano C; Quattrini, Angelo; Alessio, Massimo

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V. All rights reserved.

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

Energy Technology Data Exchange (ETDEWEB)

Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

1990-01-01

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 {plus minus} 1.8 to 28.1 {plus minus} 6.8 (NS) at 3-day postirradiation, 37.7 {plus minus} 1.9 (P less than .001) at 6-day postirradiation, and 43.8 {plus minus} 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity.

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

Science.gov (United States)

Foe, Victoria E.; von Dassow, George

2008-01-01

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

Scapular Kinematics: A Comparison between Females with and Without General Hypermobility Syndrome in Arm Elevation

Directory of Open Access Journals (Sweden)

Salman Nazary-Moghadam

2010-07-01

Full Text Available Objective: Numerous studies showed increasing incidence of acute or recurrent dislocations of the shoulder joint in people with General Hypermobility Syndrome (GHS. Given the critical role of scapular orientation in function of shoulder, the aim of this study is to compare the parameters indicating position and orientation of scapula between females with and without General Hypermobility Syndrome in frontal and sagital plane in arm elevation. Materials & Methods: In this cross sectional and case-control study, 16 females with General Hypermobility Syndrome were selected simply and conveniently and 16 healthy females were selected and matched by age, body mass index and menstrual status. A three dimensional motion analysis system (vicon 460 was used to measure scapular position (upper-lower and medial-lateral translations and orientation (upward rotation, posterior tilt and internal rotation angle. Measurement were taken with the arm placed in different angles of arm elevation. Date analysis was performed with Independent T test. Results: Upward rotation angles in sagital plane in 90º (P=0.03, 120º (P=0.01 and full range of arm elevation (P=0.04 were lower in case group as compared to control group. Also patients with General Hypermobility Syndrome showed a lesser amount of lateral scapular translation in 90º (P=0.02 and full range of sagital plane arm elevation (P=0.02. In addition, lateral scapular translation in 120º (P=0.02 and full range of frontal plane arm elevation (P=0.01 was lower in case group compared with control group. Conclusion: Altered kinematics in General Hypermobility Syndrome has a greater role in shoulder injuries and neuromuscular defect  seems to be an underlying cause of scapular kinematics' changes in people with hypermobility syndrome.

Botulinum Toxin Type A Inhibits α-Smooth Muscle Actin and Myosin II Expression in Fibroblasts Derived From Scar Contracture.

Science.gov (United States)

Chen, Minliang; Yan, Tongtong; Ma, Kui; Lai, Linying; Liu, Chang; Liang, Liming; Fu, Xiaobing

2016-09-01

Scar contracture (SC) is one of the most common complications resulting from major burn injuries. Numerous treatments are currently available but they do not always yield excellent therapeutic results. Recent reports suggest that botulinum toxin type A (BTXA) is effective at reducing SC clinically, but the molecular mechanism for this action is unknown. α-Smooth muscle actin (α-SMA) and myosin II are the main components of stress fibers, which are the contractile structures of fibroblasts. The effects of BTXA on α-SMA and myosin II in SC are still unknown. This study aimed to explore the effect of BTXA on α-SMA and myosin II expression in fibroblasts derived from SC and to elucidate its actual mechanism further. Fibroblasts were isolated from tissue specimens of SC. Fibroblasts were cultured in Dulbecco modified Eagle medium with different concentrations of BTXA and their proliferation was analyzed through the tetrazolium-based colorimetric method at 1, 4, and 7 days. Proteins of α-SMA and myosin II were checked using Western blot in fibroblasts treated with different concentrations of BTXA at 1, 4, and 7 days. Fibroblasts without BTXA treatment had a higher proliferation than that in other groups, which indicated that the proliferation of fibroblasts was significantly inhibited by BTXA (P < 0.05). Proteins of α-SMA and myosin II between fibroblasts with BTXA and fibroblasts without BTXA are statistically significant (P < 0.05). These results suggest that BTXA effectively inhibited the growth of fibroblasts derived from SC and reduced the expression of α-SMA and myosin II, which provided theoretical support for the application of BTXA to control SC.

Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin

DEFF Research Database (Denmark)

Kriajevska, M; Bronstein, I B; Scott, D J

2000-01-01

a regulatory role in the myosin assembly. In the presence of calcium, Mts1 binds at the C-terminal end of the myosin heavy chain close to the site of phosphorylation by protein kinase CK2 (Ser1944). In the present study, we have shown that interaction of Mts1 with the human platelet myosin or C...

Kinematics/statics analysis of a novel serial-parallel robotic arm with hand

Energy Technology Data Exchange (ETDEWEB)

Lu, Yi; Dai, Zhuohong; Ye, Nijia; Wang, Peng [Yanshan University, Hebei (China)

2015-10-15

A robotic arm with fingered hand generally has multi-functions to complete various complicated operations. A novel serial-parallel robotic arm with a hand is proposed and its kinematics and statics are studied systematically. A 3D prototype of the serial-parallel robotic arm with a hand is constructed and analyzed by simulation. The serial-parallel robotic arm with a hand is composed of an upper 3RPS parallel manipulator, a lower 3SPR parallel manipulator and a hand with three finger mechanisms. Its kinematics formulae for solving the displacement, velocity, acceleration of are derived. Its statics formula for solving the active/constrained forces is derived. Its reachable workspace and orientation workspace are constructed and analyzed. Finally, an analytic example is given for solving the kinematics and statics of the serial-parallel robotic arm with a hand and the analytic solutions are verified by a simulation mechanism.

Kinematics/statics analysis of a novel serial-parallel robotic arm with hand

International Nuclear Information System (INIS)

Lu, Yi; Dai, Zhuohong; Ye, Nijia; Wang, Peng

2015-01-01

A robotic arm with fingered hand generally has multi-functions to complete various complicated operations. A novel serial-parallel robotic arm with a hand is proposed and its kinematics and statics are studied systematically. A 3D prototype of the serial-parallel robotic arm with a hand is constructed and analyzed by simulation. The serial-parallel robotic arm with a hand is composed of an upper 3RPS parallel manipulator, a lower 3SPR parallel manipulator and a hand with three finger mechanisms. Its kinematics formulae for solving the displacement, velocity, acceleration of are derived. Its statics formula for solving the active/constrained forces is derived. Its reachable workspace and orientation workspace are constructed and analyzed. Finally, an analytic example is given for solving the kinematics and statics of the serial-parallel robotic arm with a hand and the analytic solutions are verified by a simulation mechanism.

Special Gripper for a Robotic Arm

Directory of Open Access Journals (Sweden)

Miguel Angel SELLES

2012-12-01

Full Text Available New structures for gripping objects in robotic manipulation processes are oriented to the new arrangement of mechanical structures using new materials and processing technologies and innovative procedures for the implementation of contact gripping element links to an object with a high degree of adaptively of applications together with the ability to alter the structure of grip and limiting the intensity of the contact stiffness variation of snap elements custody and pliability. The application of elastomeric materials and surface finishes is important. This paper presents both a new gripper design for robot arms but also the search of the selected materials to make an experimental evaluation of technical parameters that are used to assess their application potential and suitability for the targeted applications. Also the results and conclusions for gripper testing in manipulation operations with two different robot arms are presented.

Characteristics of myosin profile in human vastus lateralis muscle in relation to training background.

Science.gov (United States)

Zawadowska, B; Majerczak, J; Semik, D; Karasinski, J; Kolodziejski, L; Kilarski, W M; Duda, K; Zoladz, J A

2004-01-01

Twenty-four male volunteers (mean +/- SD: age 25.4+/-5.8 years, height 178.6+/-5.5 cm, body mass 72.1+/-7.7 kg) of different training background were investigated and classified into three groups according to their physical activity and sport discipline: untrained students (group A), national and sub-national level endurance athletes (group B, 7.8+/-2.9 years of specialised training) and sprint-power athletes (group C, 12.8+/-8.7 years of specialised training). Muscle biopsies of vastus lateralis were analysed histochemically for mATPase and SDH activities, immunohistochemically for fast and slow myosin, and electrophoretically followed by Western immunoblotting for myosin heavy chain (MyHC) composition. Significant differences (Pski-jumping, volleyball, soccer and modern dance. Furthermore, the relative amount of the fastest MyHCIIX isoform in vastus lateralis muscle was significantly lower in the athletes from group C than in students (group A). We conclude that the myosin profile in the athletes belonging to group C was unfavourable for their sport disciplines. This could be the reason why those athletes did not reach international level despite of several years of training.

Myosin content of single muscle fibers following short-term disuse and active recovery in young and old healthy men

DEFF Research Database (Denmark)

Hvid, Lars G; Brocca, Lorenza; Ørtenblad, Niels

2017-01-01

healthy men. Following disuse, myosin content decreased (p... young and old in both fiber types, with MHC 2a fibers demonstrating an overshooting in young (+31%, pStrong correlations were observed between myosin content and single fiber SF in both young and old, with greater slope steepness in MHC 2a vs 1 fibers indicating an enhanced intrinsic...

Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

Directory of Open Access Journals (Sweden)

Tolliday Nicola J

2006-06-01

Full Text Available Abstract Background All eukaryotes with the exception of plants use an actomyosin ring to generate a constriction force at the site of cell division (cleavage furrow during mitosis and meiosis. The structure and filament forming abilities located in the C-terminal or tail region of one of the main components, myosin II, are important for localising the molecule to the contractile ring (CR during cytokinesis. However, it remains poorly understood how myosin II is recruited to the site of cell division and how this recruitment relates to myosin filament assembly. Significant conservation between species of the components involved in cytokinesis, including those of the CR, allows the use of easily genetically manipulated organisms, such as budding yeast (Saccharomyces cerevisiae, in the study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1. Unlike most other class II myosins, the tail of Myo1 has an irregular coiled coil. In this report we use molecular genetics, biochemistry and live cell imaging to characterize the minimum localisation domain (MLD of budding yeast Myo1. Results We show that the MLD is a small region in the centre of the tail of Myo1 and that it is both necessary and sufficient for localisation of Myo1 to the yeast bud neck, the pre-determined site of cell division. Hydrodynamic measurements of the MLD, purified from bacteria or yeast, show that it is likely to exist as a trimer. We also examine the importance of a small region of low coiled coil forming probability within the MLD, which we call the hinge region. Removal of the hinge region prevents contraction of the CR. Using fluorescence recovery after photobleaching (FRAP, we show that GFP-tagged MLD is slightly more dynamic than the GFP-tagged full length molecule but less dynamic than the GFP-tagged Myo1 construct lacking the hinge region. Conclusion Our results define the intrinsic determinant for the localization of budding yeast myosin II and show

Spectral and spatial properties of polarized light reflections from the arms of squid (Loligo pealeii) and cuttlefish (Sepia officinalis L.).

Science.gov (United States)

Chiou, Tsyr-Huei; Mäthger, Lydia M; Hanlon, Roger T; Cronin, Thomas W

2007-10-01

On every arm of cuttlefish and squid there is a stripe of high-reflectance iridophores that reflects highly polarized light. Since cephalopods possess polarization vision, it has been hypothesized that these polarized stripes could serve an intraspecific communication function. We determined how polarization changes when these boneless arms move. By measuring the spectral and polarizing properties of the reflected light from samples at various angles of tilt and rotation, we found that the actual posture of the arm has little or no effect on partial polarization or the e-vector angle of the reflected light. However, when the illumination angle changed, the partial polarization of the reflected light also changed. The spectral reflections of the signals were also affected by the angle of illumination but not by the orientation of the sample. Electron microscope samples showed that these stripes are composed of several groups of multilayer platelets within the iridophores. The surface normal to each group is oriented at a different angle, which produces essentially constant reflection of polarized light over a range of viewing angles. These results demonstrate that cuttlefish and squid could send out reliable polarization signals to a receiver regardless of arm orientation.

IE Information Notice No. 85-93: Westinghouse Type DS circuit breakers, potential failure of electric closing feature because of broken spring release latch lever

International Nuclear Information System (INIS)

Jordan, E.L.

1992-01-01

On April 14, 1985, the Westinghouse Nuclear Services Integration Division (NSID) issued Technical Bulletin No. NSID-TB-85-17 advising their customers of a potential malfunction in Westinghouse Type DS Class 1E circuit breakers because of broken spring release latch levers. These electrically operated type DS breakers will not close electrically when the spring release latch lever has been broken off. Twenty-five broken levers have been reported and evaluated. This evaluation shows concentrations of incidents traceable to manufacturing in the following periods of time: early 1975, April 1976, and early 1978. This circuit breaker failure, as discussed, adversely affects the safety function (closing on demand) when the circuit breaker is used in the Engineered Safety Features Systems. However, this failure mode will not affect the safety trip function when it is used in the reactor protection system

Identification and biochemical analysis of Slac2-c/MyRIP as a Rab27A-, myosin Va/VIIa-, and actin-binding protein.

Science.gov (United States)

Kuroda, Taruho S; Fukuda, Mitsunori

2005-01-01

Slac2-c/MyRIP is a specific Rab27A-binding protein that contains an N-terminal synaptotagmin-like protein (Slp) homology domain (SHD, a newly identified GTP-Rab27A-binding motif), but in contrast to the Slp family proteins, it lacks C-terminal tandem C2 domains. In vitro Slac2-c simultaneously directly interacts with both Rab27A and an actin-based motor protein, myosin Va, via its N-terminal SHD and middle region, respectively, consistent with the fact that the overall structure of Slac2-c is similar to that of Slac2-a/melanophilin, a linker protein between Rab27A and myosin Va in the melanosome transport in melanocytes. Unlike Slac2-a, however, the middle region of Slac2-c interacts with two types of myosins, myosin Va and myosin VIIa. In addition, the most C-terminal part of both Slac2-a and Slac2-c functions as an actin-binding domain: it directly interacts with globular and fibrous actin in vitro, and the actin-binding domain of Slac2-a and Slac2-c colocalizes with actin filaments when it is expressed in living cells (i.e., PC12 cells and mouse melanocytes). In this chapter we describe the methods that have been used to analyze the protein-protein interactions of Slac2-c, specifically with Rab27A, myosin Va/VIIa, and actin.

Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.

Science.gov (United States)

el-Amraoui, A; Sahly, I; Picaud, S; Sahel, J; Abitbol, M; Petit, C

1996-08-01

Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks.

Confinement Sensing and Signal Optimization via Piezo1/PKA and Myosin II Pathways

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Wei-Chien Hung

2016-05-01

Full Text Available Summary: Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca2+ level is increased, leading to phosphodiesterase 1 (PDE1-dependent suppression of PKA activity. This Ca2+ elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments. : Hung et al. demonstrate that a Piezo1-dependent intracellular calcium increase negatively regulates protein kinase A (PKA as cells transit from unconfined to confined spaces. The Piezo1/PKA and myosin II signaling modules constitute two confinement-sensing mechanisms. This study provides a paradigm by which signaling enables cells to sense and adapt to different microenvironments.

Parrotfish grazing ability: interspecific differences in relation to jaw-lever mechanics and relative weight of adductor mandibulae on an Okinawan coral reef

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Atsushi Nanami

2016-09-01

Full Text Available Parrotfishes (family Labridae: Scarini are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing. The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight defined as the grazing ability index (GAI. There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni. Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests

Parrotfish grazing ability: interspecific differences in relation to jaw-lever mechanics and relative weight of adductor mandibulae on an Okinawan coral reef.

Science.gov (United States)

Nanami, Atsushi

2016-01-01

Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the

Diseño de mecanismos de palancas asistido por computadora. // Computer Aided Design of lever mechanisms.

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J. L. Betancourt Herrera

2001-07-01

Full Text Available En la práctica del diseño industrial hay múltiples problemas que requieren de la creación de un mecanismo concaracterísticas de movimiento peculiares. La elección de un método que permita la síntesis estructural, el planteamiento ysolución de las ecuaciones correspondientes, requeridas para el análisis cinemático de los mecanismos de palancas, en unaforma clara y simple, es un problema muy complejo de resolver en sentido general.Tomando como referencia la teoría para la formación de los grupos de Assur, el autor desarrolló el método de los gruposestructurales y sobre esta base el software DSM (Diseño y Simulación de Mecanismos, que es la herramienta de cómputopropuesta para apoyar al diseñador en el proceso de Diseño Cualitativo de Mecanismos de Palancas Asistido porComputadora, que consiste en un proceso iterativo entre síntesis y análisis con el que se pueden obtener los resultados de lavariación de la estructura de un mecanismo y de sus parámetros fundamentales, prácticamente en tiempo real.En el presente trabajo se definen y ejemplifican los conceptos y elementos principales relacionados con el diseñocualitativo de mecanismos de palancas asistido por computadora.Palabras claves: CAD, mecanismos de palancas, diseño industrial, análisis cinemático, síntesis estructural.___________________________________________________________________________AbstractThere are series of problems in industrial design practice that require a mechanism with specific characteristic movement.Selecting a method for achieving a clear and simple structural synthesis and cinematic analysis of lever mechanisms isgenerally understood as a hard-solving problem. Based on Assur´s Group Forming Theory, the author developed theStructural Groups Method and the DSM software (Design and Simulation of Mechanisms. This software is a tool intendedto help designers in the process of Computer Assisted Qualitative Design of Lever Mechanisms. It consists

SMC Progressively Aligns Chromosomal Arms in Caulobacter crescentus but Is Antagonized by Convergent Transcription

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Ngat T. Tran

2017-08-01

Full Text Available The structural maintenance of chromosomes (SMC complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the mechanism of SMC-mediated alignment of chromosomal arms remains elusive. Here, using genome-wide methods and microscopy of single cells, we show that Caulobacter SMC is recruited to the centromeric parS site and that SMC-mediated arm alignment depends on the chromosome-partitioning protein ParB. We provide evidence that SMC likely tethers the parS-proximal regions of the chromosomal arms together, promoting arm alignment. Furthermore, we show that highly transcribed genes near parS that are oriented against SMC translocation disrupt arm alignment, suggesting that head-on transcription interferes with SMC translocation. Our results demonstrate a tight interdependence of bacterial chromosome organization and global patterns of transcription.

Braking System for Wind Turbines

Science.gov (United States)

Krysiak, J. E.; Webb, F. E.

1987-01-01

Operating turbine stopped smoothly by fail-safe mechanism. Windturbine braking systems improved by system consisting of two large steel-alloy disks mounted on high-speed shaft of gear box, and brakepad assembly mounted on bracket fastened to top of gear box. Lever arms (with brake pads) actuated by spring-powered, pneumatic cylinders connected to these arms. Springs give specific spring-loading constant and exert predetermined load onto brake pads through lever arms. Pneumatic cylinders actuated positively to compress springs and disengage brake pads from disks. During power failure, brakes automatically lock onto disks, producing highly reliable, fail-safe stops. System doubles as stopping brake and "parking" brake.

Wave Energy, Lever Operated Pivoting Float LOPF Study

DEFF Research Database (Denmark)

Margheritini, Lucia

The fully instrumented Resen Waves Lever Operated Pivoting Float LOPF wave energy buoy model has gone through the first stage of testing in regular waves in scale 1:25 of the North Sea wave conditions, in the 3D deep wave basin at the Hydraulic and Coastal Engineering Laboratory of Aalborg...... University in Denmark. The model size was 60cm W x 90cm L x 21cm H. The 60 cm width pointed towards the wave front. The LOPF buoy is characterized by a simple mechanical design with few moving parts and direct electrical output and it is taut moored to the sea bed, so all forces are referenced to the seabed...... for maximum energy output in regular as well as irregular waves. During storms the buoy pivots and streamlines itself to minimize loads on the mooring line. A conservative estimate shows that a full scale system for North Sea conditions has a float size width of 15 m that will, with 60% generator efficiency...

Lack of replication for the myosin-18B association with mathematical ability in independent cohorts

Science.gov (United States)

Pettigrew, K A; Fajutrao Valles, S F; Moll, K; Northstone, K; Ring, S; Pennell, C; Wang, C; Leavett, R; Hayiou-Thomas, M E; Thompson, P; Simpson, N H; Fisher, S E; Whitehouse, A J O; Snowling, M J; Newbury, D F; Paracchini, S

2015-01-01

Twin studies indicate that dyscalculia (or mathematical disability) is caused partly by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities and the only one reaching genome-wide statistical significance. We conducted a replication study in different cohorts to assess the effect of rs133885 maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC), (N = 3819). We tested additional cohorts including the York Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine Cohort, and stratified them for a definition of dyslexia whenever possible. We did not observe any associations between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results suggest that the myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities. PMID:25778778

The effect of the substitution of D{sub 2}O for H{sub 2}O on the degradation of myosin {beta} in solution by heat and by {sup 60}Co {gamma} radiation (1962); Effet de la substitution de D{sub 2}O a H{sub 2}O sur l'alteration de la Myosine B en solution par la chaleur et par les rayons {gamma} du {sup 60}CO (1962)

Energy Technology Data Exchange (ETDEWEB)

Pinset-Harstrom, I.; Fritsch, A. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1962-07-01

(1) Alterations of myosin B produced by heat or irradiation are shown to be qualitatively identical as demonstrated by analytical centrifugation. (2) A considerable isotope effect was demonstrated using 75 per cent D{sub 2}O in the solvent. The sensitivity of myosin B to heat and irradiation is discussed in the light of this isotope effect. (3) Polymers appearing upon heat treatment of myosin B seem to be of a very different nature than the polymers occurring alter a similar treatment upon myosin A. Polymers obtained from myosin B can be depolymerized by ATP and they appear in a much narrower temperature range than myosin A polymers. This fact indicates a considerable difference in the activation enthalpies in the two reactions. (authors) [French] (1) Cette etude montre que les alterations de la myosine B provoquees par la chaleur et par l'irradiation aux rayons {gamma} sont - telles qu'elles apparaissent a l'ultracentrifugation analytique - qualitativement semblables. (2) Nous avons observe un effet isotopique considerable de la presence de 75 pour cent de D{sub 2}O dans le solvant sur la sensibilite de la myosine B envers ces deux agents, et nous avons presente une tentative d'explication de ce fait. (3) Les polymeres qui apparaissent apres un traitement par la chaleur de la myosine semblent etre d'une nature tres differente des polymeres que l'on voit apparaitre apres un traitement identique de la myosine A. Ceux obtenus a partir de le myosine B sont depolymerisables par l'intermediaire de l'ATP et apparaissent dans une zone de temperature beaucoup plus etroite que celles de la myosine A. Ce dernier fait indique une difference considerable de l'enthalpie d'activation des deux reactions. (auteurs)

The effect of the substitution of D{sub 2}O for H{sub 2}O on the degradation of myosin {beta} in solution by heat and by {sup 60}Co {gamma} radiation (1962); Effet de la substitution de D{sub 2}O a H{sub 2}O sur l'alteration de la Myosine B en solution par la chaleur et par les rayons {gamma} du {sup 60}CO (1962)

Energy Technology Data Exchange (ETDEWEB)

Pinset-Harstrom, I; Fritsch, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1962-07-01

(1) Alterations of myosin B produced by heat or irradiation are shown to be qualitatively identical as demonstrated by analytical centrifugation. (2) A considerable isotope effect was demonstrated using 75 per cent D{sub 2}O in the solvent. The sensitivity of myosin B to heat and irradiation is discussed in the light of this isotope effect. (3) Polymers appearing upon heat treatment of myosin B seem to be of a very different nature than the polymers occurring alter a similar treatment upon myosin A. Polymers obtained from myosin B can be depolymerized by ATP and they appear in a much narrower temperature range than myosin A polymers. This fact indicates a considerable difference in the activation enthalpies in the two reactions. (authors) [French] (1) Cette etude montre que les alterations de la myosine B provoquees par la chaleur et par l'irradiation aux rayons {gamma} sont - telles qu'elles apparaissent a l'ultracentrifugation analytique - qualitativement semblables. (2) Nous avons observe un effet isotopique considerable de la presence de 75 pour cent de D{sub 2}O dans le solvant sur la sensibilite de la myosine B envers ces deux agents, et nous avons presente une tentative d'explication de ce fait. (3) Les polymeres qui apparaissent apres un traitement par la chaleur de la myosine semblent etre d'une nature tres differente des polymeres que l'on voit apparaitre apres un traitement identique de la myosine A. Ceux obtenus a partir de le myosine B sont depolymerisables par l'intermediaire de l'ATP et apparaissent dans une zone de temperature beaucoup plus etroite que celles de la myosine A. Ce dernier fait indique une difference considerable de l'enthalpie d'activation des deux reactions. (auteurs)

A New Artificial Neural Network Approach in Solving Inverse Kinematics of Robotic Arm (Denso VP6242

Directory of Open Access Journals (Sweden)

Ahmed R. J. Almusawi

2016-01-01

Full Text Available This paper presents a novel inverse kinematics solution for robotic arm based on artificial neural network (ANN architecture. The motion of robotic arm is controlled by the kinematics of ANN. A new artificial neural network approach for inverse kinematics is proposed. The novelty of the proposed ANN is the inclusion of the feedback of current joint angles configuration of robotic arm as well as the desired position and orientation in the input pattern of neural network, while the traditional ANN has only the desired position and orientation of the end effector in the input pattern of neural network. In this paper, a six DOF Denso robotic arm with a gripper is controlled by ANN. The comprehensive experimental results proved the applicability and the efficiency of the proposed approach in robotic motion control. The inclusion of current configuration of joint angles in ANN significantly increased the accuracy of ANN estimation of the joint angles output. The new controller design has advantages over the existing techniques for minimizing the position error in unconventional tasks and increasing the accuracy of ANN in estimation of robot’s joint angles.

A New Artificial Neural Network Approach in Solving Inverse Kinematics of Robotic Arm (Denso VP6242)

Science.gov (United States)

Dülger, L. Canan; Kapucu, Sadettin

2016-01-01

This paper presents a novel inverse kinematics solution for robotic arm based on artificial neural network (ANN) architecture. The motion of robotic arm is controlled by the kinematics of ANN. A new artificial neural network approach for inverse kinematics is proposed. The novelty of the proposed ANN is the inclusion of the feedback of current joint angles configuration of robotic arm as well as the desired position and orientation in the input pattern of neural network, while the traditional ANN has only the desired position and orientation of the end effector in the input pattern of neural network. In this paper, a six DOF Denso robotic arm with a gripper is controlled by ANN. The comprehensive experimental results proved the applicability and the efficiency of the proposed approach in robotic motion control. The inclusion of current configuration of joint angles in ANN significantly increased the accuracy of ANN estimation of the joint angles output. The new controller design has advantages over the existing techniques for minimizing the position error in unconventional tasks and increasing the accuracy of ANN in estimation of robot's joint angles. PMID:27610129

A New Artificial Neural Network Approach in Solving Inverse Kinematics of Robotic Arm (Denso VP6242).

Science.gov (United States)

Almusawi, Ahmed R J; Dülger, L Canan; Kapucu, Sadettin

2016-01-01

This paper presents a novel inverse kinematics solution for robotic arm based on artificial neural network (ANN) architecture. The motion of robotic arm is controlled by the kinematics of ANN. A new artificial neural network approach for inverse kinematics is proposed. The novelty of the proposed ANN is the inclusion of the feedback of current joint angles configuration of robotic arm as well as the desired position and orientation in the input pattern of neural network, while the traditional ANN has only the desired position and orientation of the end effector in the input pattern of neural network. In this paper, a six DOF Denso robotic arm with a gripper is controlled by ANN. The comprehensive experimental results proved the applicability and the efficiency of the proposed approach in robotic motion control. The inclusion of current configuration of joint angles in ANN significantly increased the accuracy of ANN estimation of the joint angles output. The new controller design has advantages over the existing techniques for minimizing the position error in unconventional tasks and increasing the accuracy of ANN in estimation of robot's joint angles.

The force dependence of isometric and concentric potentiation in mouse muscle with and without skeletal myosin light chain kinase.

Science.gov (United States)

Gittings, William; Aggarwal, Harish; Stull, James T; Vandenboom, Rene

2015-01-01

The isometric potentiation associated with myosin phosphorylation is force dependent. The purpose of this study was to assess the influence of a pre-existing period of isometric force on the concentric force potentiation displayed by mouse muscles with and without the ability to phosphorylate myosin. We tested isometric (ISO) and concentric (CON) potentiation, as well as concentric potentiation after isometric force (ISO-CON), in muscles from wild-type (WT) and skeletal myosin light chain kinase-deficient (skMLCK(-/-)) mice. A conditioning stimulus increased (i.e., potentiated) mean concentric force in the ISO-CON and CON conditions to 1.31 ± 0.02 and 1.35 ± 0.02 (WT) and to 1.19 ± 0.02 and 1.21 ± 0.01 (skMLCK(-/-)) of prestimulus levels, respectively (data n = 6-8, p muscles.

Sterile Reverse Osmosis Water Combined with Friction Are Optimal for Channel and Lever Cavity Sample Collection of Flexible Duodenoscopes

Directory of Open Access Journals (Sweden)

Michelle J. Alfa

2017-11-01

Full Text Available IntroductionSimulated-use buildup biofilm (BBF model was used to assess various extraction fluids and friction methods to determine the optimal sample collection method for polytetrafluorethylene channels. In addition, simulated-use testing was performed for the channel and lever cavity of duodenoscopes.Materials and methodsBBF was formed in polytetrafluorethylene channels using Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Sterile reverse osmosis (RO water, and phosphate-buffered saline with and without Tween80 as well as two neutralizing broths (Letheen and Dey–Engley were each assessed with and without friction. Neutralizer was added immediately after sample collection and samples concentrated using centrifugation. Simulated-use testing was done using TJF-Q180V and JF-140F Olympus duodenoscopes.ResultsDespite variability in the bacterial CFU in the BBF model, none of the extraction fluids tested were significantly better than RO. Borescope examination showed far less residual material when friction was part of the extraction protocol. The RO for flush-brush-flush (FBF extraction provided significantly better recovery of E. coli (p = 0.02 from duodenoscope lever cavities compared to the CDC flush method.Discussion and conclusionWe recommend RO with friction for FBF extraction of the channel and lever cavity of duodenoscopes. Neutralizer and sample concentration optimize recovery of viable bacteria on culture.

Expression of porcine myosin heavy chain 1 gene in Berkshire loins ...

African Journals Online (AJOL)

Expression of porcine myosin heavy chain 1 gene in Berkshire loins with a high pH24 value. Jin Hun Kang, Woo Young Bang, Eun Jung Kwon, Yong Hwa Lee, Da Hye Park, Eun Seok Cho, Min Ji Kim, Jong-Soon Choi, Hwa Chun Park, Beom Young Park, Chul Wook Kim ...

Regulation of nonmuscle myosin II during 3-methylcholanthrene induced dedifferentiation of C2C12 myotubes

Energy Technology Data Exchange (ETDEWEB)

Dey, Sumit K.; Saha, Shekhar; Das, Provas; Das, Mahua R.; Jana, Siddhartha S., E-mail: bcssj@iacs.res.in

2014-08-01

3-Methylcholanthrene (3MC) induces tumor formation at the site of injection in the hind leg of mice within 110 days. Recent reports reveal that the transformation of normal muscle cells to atypical cells is one of the causes for tumor formation, however the molecular mechanism behind this process is not well understood. Here, we show in an in vitro study that 3MC induces fragmentation of multinucleate myotubes into viable mononucleates. These mononucleates form colonies when they are seeded into soft agar, indicative of cellular transformation. Immunoblot analysis reveals that phosphorylation of myosin regulatory light chain (RLC{sub 20}) is 5.6±0.5 fold reduced in 3MC treated myotubes in comparison to vehicle treated myotubes during the fragmentation of myotubes. In contrast, levels of myogenic factors such as MyoD, Myogenin and cell cycle regulators such as Cyclin D, Cyclin E1 remain unchanged as assessed by real-time PCR array and reverse transcriptase PCR analysis, respectively. Interestingly, addition of the myosin light chain kinase inhibitor, ML-7, enhances the fragmentation, whereas phosphatase inhibitor perturbs the 3MC induced fragmentation of myotubes. These results suggest that decrease in RLC{sub 20} phosphorylation may be associated with the fragmentation step of dedifferentiation. - Highlights: • 3-Methylcholanthrene induces fragmentation of C2C12-myotubes. • Dedifferentiation can be divided into two steps – fragmentation and proliferation. • Fragmentation is associated with rearrangement of nonmuscle myosin II. • Genes associated with differentiation and proliferation are not altered during fragmentation. • Phosphorylation of myosin regulatory light chain is reduced during fragmentation.

Human arm stiffness and equilibrium-point trajectory during multi-joint movement.

Science.gov (United States)

Gomi, H; Kawato, M

1997-03-01

By using a newly designed high-performance manipulandum and a new estimation algorithm, we measured human multi-joint arm stiffness parameters during multi-joint point-to-point movements on a horizontal plane. This manipulandum allows us to apply a sufficient perturbation to subject's arm within a brief period during movement. Arm stiffness parameters were reliably estimated using a new algorithm, in which all unknown structural parameters could be estimated independent of arm posture (i.e., constant values under any arm posture). Arm stiffness during transverse movement was considerably greater than that during corresponding posture, but not during a longitudinal movement. Although the ratios of elbow, shoulder, and double-joint stiffness were varied in time, the orientation of stiffness ellipses during the movement did not change much. Equilibrium-point trajectories that were predicted from measured stiffness parameters and actual trajectories were slightly sinusoidally curved in Cartesian space and their velocity profiles were quite different from the velocity profiles of actual hand trajectories. This result contradicts the hypothesis that the brain does not take the dynamics into account in movement control depending on the neuromuscular servo mechanism; rather, it implies that the brain needs to acquire some internal models of controlled objects.

Acceleration of the sliding movement of actin filaments with the use of a non-motile mutant myosin in in vitro motility assays driven by skeletal muscle heavy meromyosin.

Directory of Open Access Journals (Sweden)

Kohei Iwase

Full Text Available We examined the movement of an actin filament sliding on a mixture of normal and genetically modified myosin molecules that were attached to a glass surface. For this purpose, we used a Dictyostelium G680V mutant myosin II whose release rates of Pi and ADP were highly suppressed relative to normal myosin, leading to a significantly extended life-time of the strongly bound state with actin and virtually no motility. When the mixing ratio of G680V mutant myosin II to skeletal muscle HMM (heavy myosin was 0.01%, the actin filaments moved intermittently. When they moved, their sliding velocities were about two-fold faster than the velocity of skeletal HMM alone. Furthermore, sliding movements were also faster when the actin filaments were allowed to slide on skeletal muscle HMM-coated glass surfaces in the motility buffer solution containing G680V HMM. In this case no intermittent movement was observed. When the actin filaments used were copolymerized with a fusion protein consisting of Dictyostelium actin and Dictyostelium G680V myosin II motor domain, similar faster sliding movements were observed on skeletal muscle HMM-coated surfaces. The filament sliding velocities were about two-fold greater than the velocities of normal actin filaments. We found that the velocity of actin filaments sliding on skeletal muscle myosin molecules increased in the presence of a non-motile G680V mutant myosin motor.

Energy integration: Regional economic integration lever and possible insertion factor in the global economy

International Nuclear Information System (INIS)

Lokolo, M.C.

2001-01-01

In the 1920s, just after the War, an idea began taking root in the Old Continent, to build what could be described as the United States of Europe. Thirty years later, in 1951, a new source of energy, coal, paved the way for the economic integration of Europe. It culminated into monetary integration in January 2002. Economic integration makes sense in the context of the relatively small size of some national economies and markets, and the judicious utilization of rare resources and their unequal distribution. In this document, the author elaborated on the principles at play in economic integration and argued that the integration of the national energy markets could be the lever for economic integration through the gradual elimination of the various obstacles to trade. The author first presented a brief historical overview of economic integration from the perspective of global economic relationships, covering the period between the two world wars to the General Agreement on Tariffs and Trade (GATT) to the World Trade Organization (WTO). The concept and the forms of economic integration were reviewed. Energy integration as a lever of regional economic integration and as a factor in global economic insertion were discussed. Energy integration is a tool for the improvement of the human condition. 15 refs

Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: Mediation by cyclic AMP

International Nuclear Information System (INIS)

Egan, J.J.; Gronowicz, G.; Rodan, G.A.

1991-01-01

Parathyroid hormone (PTH) alters the shape of osteoblastic cells both in vivo and in vitro. In this study, we examined the effect of PTH on cytoskeletal actin and myosin, estimated by polyacrylamide gel electrophoresis of Triton X-100 (1%) nonextractable proteins. After 2-5 minutes, PTH caused a rapid and transient decrease of 50-60% in polymerized actin and myosin associated with the Triton X-100 nonextractable cytoskeleton. Polymerized actin returned to control levels by 30 min. The PTH effect was dose-dependent with an IC50 of about 1 nM, and was partially inhibited by the (3-34) PTH antagonist. PTH caused a rapid transient rise in cyclic AMP (cAMP) in these cells that peaked at 4 min, while the nadir in cytoskeletal actin and myosin was recorded around 5 min. The intracellular calcium chelator Quin-2/AM (10 microM) also decreased cytoskeletal actin and myosin, to the same extent as did PTH (100 nM). To distinguish between cAMP elevation and Ca++ reduction as mediators of PTH action, we measured the phosphorylation of the 20 kD (PI 4.9) myosin light chain in cells preincubated with [32P]-orthophosphate. The phosphorylation of this protein decreased within 2-3 min after PTH addition and returned to control levels after 5 min. The calcium ionophore A-23187 did not antagonize this PTH effect. Visualization of microfilaments with rhodamine-conjugated phalloidin showed that PTH altered the cytoskeleton by decreasing the number of stress fibers. These changes in the cytoskeleton paralleled changes in the shape of the cells from a spread configuration to a stellate form with retracting processes. The above findings indicate that the alteration in osteoblast shape produced by PTH involve relatively rapid and transient changes in cytoskeletal organization that appear to be mediated by cAMP

Dual Arm Work Module Development and Appplications

Energy Technology Data Exchange (ETDEWEB)

Noakes, M.W.

1999-04-25

The dual arm work module (DAWM) was developed at Oak Ridge National Laboratory (ORNL) by the Robotics Technology Development Program (RTDP) as a development test bed to study issues related to dual arm manipulation, including platform cotilguration, controls, automation, operations, and tooling. The original platform was based on two Schilling Titan II manipulators mounted to a 5-degree-of- freedom (DOF) base fabricated by RedZone Robotics, Inc. The 5-DOF articulation provided a center torso rotation, linear actuation to change the separation between the arms, and arm base rotation joints to provide "elbows up," elbows down," or "elbows out" orientation. A series of tests were conducted on operations, tooling, and task space scene analysis (TSSA)-driven robotics for overhead transporter- mounted and crane hook-deployed scenarios. A concept was developed for DAWM deployment from a large remote work vehicle, but the project was redirected to support dismantlement of the Chicago Pile #5 (CP-5) reactor at Argonne National Laboratory in fiscal year (FY) 1997. Support of CP-5 required a change in focus of the dual arm technology from that of a development test bed to a system focussed for a specific end user. ORNL teamed with the Idaho National Environmental ,Engineering Laboratory, Sandia National Laboratory, and the Savannah River Technology Center to deliver a crane-deployed derivative of the DAWM, designated the dual arm work platform (DAWP). RTDP staff supported DAWP at CP-5 for one FY; Argonne staff continued operation through to dismantlement of the reactor internals. Lessons learned from this interaction were extensive. Beginning in FY 1999, dual arm development activities are again being pursued in the context of those lessons learned. This paper describes the progression of philosophy of the DAWM from initial test bed to lessons learned through interaction at CP-5 and to the present investigation of telerobotic assist of teleoperation and TSSA- driven robotics.

Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

Directory of Open Access Journals (Sweden)

Xinhua Zhang

Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

The Role of Control System in Increasing Corporate social Performance: The Use of Levers of Control

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Hasan Fauzi

2008-06-01

Full Text Available One important instrument to be used in the control system design is strategic behaviors that can lead to the expected organization performance.  Referring to the extended definition of strategic behavior using stakeholder-based strategic behavior, corporate social performance is kind of strategic behavior to be influenced by using control system. This paper discusses how control system, using Simons‟ levers of control can play important role in increasing the corporate social performance. The interaction between control system, including belief system, boundary system, diagnostic control system, and interactive control system, as well as the corporate financial performance (CFP can affect the corporate social performance (CSP due to fact that increase in CFP resulting from the appropriate use of control system components enables the company has more chance to do the CSP. The levers of control are deemed to form an integral part of employee socialization and support the development of an organization‟s culture, the system of shared beliefs, values, norms, and mores of organizational members which are deemed to be a primary determinant of the direction of employee behavior.

Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

Energy Technology Data Exchange (ETDEWEB)

Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany); Renkawitz-Pohl, Renate, E-mail: renkawit@biologie.uni-marburg.de [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany)

2013-02-15

Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity.

Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

International Nuclear Information System (INIS)

Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev; Renkawitz-Pohl, Renate

2013-01-01

Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity

Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

Directory of Open Access Journals (Sweden)

D.V. Vassallo

2008-09-01

Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

A coal combine

Energy Technology Data Exchange (ETDEWEB)

Wlachovsky, I; Bartos, J

1980-02-15

A design is presented for a coal combine, equipped with two drum operational units, on whose both ends of the upper surface of the body, two coal saws are mounted with the help of a lever system. These saws, found in an operational position, form a gap in the block of the coal block, which is not embraced by the drum operational unit. The coal block, found between the gap and the support, falls down onto the longwall scraper conveyor. The lever system of each coal saw is controlled by two hydraulic jacks. One of the jacks is mounted vertically on the facial wall of the body of the combine and is used for the hoisting for the required height of the horizontal arm of the lever, reinforced by one end in the hinge on the body of the combine. On the ''free'' end of that lever, a coal saw is mounted in a hinge-like fashion and which is connected by the hydraulic jack to the horizontal arm of the lever system. This hydraulic jack is used for the clamping of the coal saw to the face.

Myosin II activity is required for functional leading-edge cells and closure of epidermal sheets in fish skin ex vivo.

Science.gov (United States)

Morita, Toshiyuki; Tsuchiya, Akiko; Sugimoto, Masazumi

2011-09-01

Re-epithelialization in skin wound healing is a process in which epidermal sheets grow and close the wound. Although the actin-myosin system is thought to have a pivotal role in re-epithelialization, its role is not clear. In fish skin, re-epithelialization occurs around 500 μm/h and is 50 times faster than in mammalian skin. We had previously reported that leading-edge cells of the epidermal outgrowth have both polarized large lamellipodia and "purse string"-like actin filament cables in the scale-skin culture system of medaka fish, Oryzias latipes (Cell Tissue Res, 2007). The actin purse-string (APS) is a supracellular contractile machinery in which adherens junctions (AJs) link intracellular myosin II-including actin cables between neighboring cells. In this study, we developed a modified "face-to-face" scale-skin culture system as an ex vivo model to study epidermal wound healing, and examined the role of the actin-myosin system in the rapid re-epithelialization using a myosin II ATPase inhibitor, blebbistatin. A low level of blebbistatin suppressed the formation of APS and induced the dissociation of keratocytes from the leading edge without attenuating the growth of the epidermal sheet or the migration rate of solitary keratocytes. AJs in the superficial layer showed no obvious changes elicited by blebbistatin. However, two epidermal sheets without APSs did not make a closure with each other, which was confirmed by inhibiting the connecting AJs between the superficial layers. These results suggest that myosin II activity is required for functional leading-edge cells and for epidermal closure.

Lack of replication for the myosin-18B association with mathematical ability in independent cohorts.

Science.gov (United States)

Pettigrew, K A; Fajutrao Valles, S F; Moll, K; Northstone, K; Ring, S; Pennell, C; Wang, C; Leavett, R; Hayiou-Thomas, M E; Thompson, P; Simpson, N H; Fisher, S E; Whitehouse, A J O; Snowling, M J; Newbury, D F; Paracchini, S

2015-04-01

Twin studies indicate that dyscalculia (or mathematical disability) is caused partly by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities and the only one reaching genome-wide statistical significance. We conducted a replication study in different cohorts to assess the effect of rs133885 maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC), (N = 3819). We tested additional cohorts including the York Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine Cohort, and stratified them for a definition of dyslexia whenever possible. We did not observe any associations between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results suggest that the myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities. © 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Double phosphorylation of the myosin regulatory light chain during rigor mortis of bovine Longissimus muscle.

Science.gov (United States)

Muroya, Susumu; Ohnishi-Kameyama, Mayumi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Chikuni, Koichi

2007-05-16

To investigate changes in myosin light chains (MyLCs) during postmortem aging of the bovine longissimus muscle, we performed two-dimensional gel electrophoresis followed by identification with matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results of fluorescent differential gel electrophoresis showed that two spots of the myosin regulatory light chain (MyLC2) at pI values of 4.6 and 4.7 shifted toward those at pI values of 4.5 and 4.6, respectively, by 24 h postmortem when rigor mortis was completed. Meanwhile, the MyLC1 and MyLC3 spots did not change during the 14 days postmortem. Phosphoprotein-specific staining of the gels demonstrated that the MyLC2 proteins at pI values of 4.5 and 4.6 were phosphorylated. Furthermore, possible N-terminal region peptides containing one and two phosphoserine residues were detected in each mass spectrum of the MyLC2 spots at pI values of 4.5 and 4.6, respectively. These results demonstrated that MyLC2 became doubly phosphorylated during rigor formation of the bovine longissimus, suggesting involvement of the MyLC2 phosphorylation in the progress of beef rigor mortis. Bovine; myosin regulatory light chain (RLC, MyLC2); phosphorylation; rigor mortis; skeletal muscle.

Characteristics of myosin profile in human vastus lateralis muscle in relation to training background.

Directory of Open Access Journals (Sweden)

J A Zoladz

2004-10-01

Full Text Available Twenty-four male volunteers (mean +/- SD: age 25.4+/-5.8 years, height 178.6+/-5.5 cm, body mass 72.1+/-7.7 kg of different training background were investigated and classified into three groups according to their physical activity and sport discipline: untrained students (group A, national and sub-national level endurance athletes (group B, 7.8+/-2.9 years of specialised training and sprint-power athletes (group C, 12.8+/-8.7 years of specialised training. Muscle biopsies of vastus lateralis were analysed histochemically for mATPase and SDH activities, immunohistochemically for fast and slow myosin, and electrophoretically followed by Western immunoblotting for myosin heavy chain (MyHC composition. Significant differences (P<0.05 regarding composition of muscle fibre types and myosin heavy chains were found only between groups A (41.7+/-1.6% of MyHCI, 40.8+/-4.0% of MyHCIIA and 17.5+/-4.0% of MyHCIIX and B (64.3+/-0.8% of MyHCI, 34.0+/-1.4% of MyHCIIA and 1.7+/-1.4% of MyHCIIX and groups A and C (59.6+/-1.6% of MyHCI, 37.2+/-1.3% of MyHCIIA and 3.2+/-1.3% of MyHCIIX. Unexpectedly, endurance athletes (group B such as long-distance runners, cyclists and cross country skiers, did not differ from the athletes representing short term, high power output sports (group C such as ice hockey, karate, ski-jumping, volleyball, soccer and modern dance. Furthermore, the relative amount of the fastest MyHCIIX isoform in vastus lateralis muscle was significantly lower in the athletes from group C than in students (group A. We conclude that the myosin profile in the athletes belonging to group C was unfavourable for their sport disciplines. This could be the reason why those athletes did not reach international level despite of several years of training.

Ontogenetic changes in larval swimming and orientation of pre-competent sea urchin Arbacia punctulata in turbulence

Science.gov (United States)

Wheeler, Jeanette D.; Chan, Kit Yu Karen; Anderson, Erik J.; Mullineaux, Lauren S.

2016-01-01

ABSTRACT Many marine organisms have complex life histories, having sessile adults and relying on the planktonic larvae for dispersal. Larvae swim and disperse in a complex fluid environment and the effect of ambient flow on larval behavior could in turn impact their survival and transport. However, to date, most studies on larvae–flow interactions have focused on competent larvae near settlement. We examined the importance of flow on early larval stages by studying how local flow and ontogeny influence swimming behavior in pre-competent larval sea urchins, Arbacia punctulata. We exposed larval urchins to grid-stirred turbulence and recorded their behavior at two stages (4- and 6-armed plutei) in three turbulence regimes. Using particle image velocimetry to quantify and subtract local flow, we tested the hypothesis that larvae respond to turbulence by increasing swimming speed, and that the increase varies with ontogeny. Swimming speed increased with turbulence for both 4- and 6-armed larvae, but their responses differed in terms of vertical swimming velocity. 4-Armed larvae swam most strongly upward in the unforced flow regime, while 6-armed larvae swam most strongly upward in weakly forced flow. Increased turbulence intensity also decreased the relative time that larvae spent in their typical upright orientation. 6-Armed larvae were tilted more frequently in turbulence compared with 4-armed larvae. This observation suggests that as larvae increase in size and add pairs of arms, they are more likely to be passively re-oriented by moving water, rather than being stabilized (by mechanisms associated with increased mass), potentially leading to differential transport. The positive relationship between swimming speed and larval orientation angle suggests that there was also an active response to tilting in turbulence. Our results highlight the importance of turbulence to planktonic larvae, not just during settlement but also in earlier stages through morphology�

Economic Levers for Mitigating Interest Flooding Attack in Named Data Networking

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Licheng Wang

2017-01-01

Full Text Available As a kind of unwelcome, unavoidable, and malicious behavior, distributed denial of service (DDoS is an ongoing issue in today’s Internet as well as in some newly conceived future Internet architectures. Recently, a first step was made towards assessing DDoS attacks in Named Data Networking (NDN—one of the promising Internet architectures in the upcoming big data era. Among them, interest flooding attack (IFA becomes one of the main serious problems. Enlightened by the extensive study on the possibility of mitigating DDoS in today’s Internet by employing micropayments, in this paper we address the possibility of introducing economic levers, say, dynamic pricing mechanism, and so forth, for regulating IFA in NDN.

C-arm CT for chemo-embolization of liver tumors

International Nuclear Information System (INIS)

Huppert, P.E.; Firlbeck, G.; Meissner, O.A.; Wietholtz, H.

2009-01-01

Local efficacy of transarterial chemo-embolization (TACE) is enhanced if selective treatment is performed. Selectivity of TACE mainly depends on vascular anatomy but also on the identification and catheterization of tumor feeding arteries. Correlation of vascular territories and target tumor volume in angiographic projection images is more difficult if tumors are not hypervascularized and contrast of liver parenchyma is inhomogeneous. C-arm CT offers the option of selective perfusion imaging via tumor-feeding arteries. This allows the comparison of perfusion images and baseline cross-sectional imaging to evaluate if tumors are covered completely by local treatment and to change the catheter position if necessary. Furthermore the uptake of embolization material, such as lipiodol can be checked by C-arm CT. In a prospective study of 75 TACE of liver tumors and liver metastases we evaluated the appropriateness of 85 catheter positions ready for delivery by perfusion C-arm CT and compared the diagnostic confidence of angiography and perfusion C-arm CT in terms of judgment of correct catheter position for the planned treatment. Diagnostic confidence was improved by perfusion C-arm CT in 55% of cases and in 11 cases (13%) catheter positions were inappropriate and had to be corrected. The reasons for catheter repositioning were incomplete coverage of the target tumor by perfusion volume (mismatch) in 6 cases, inappropriate perfusion of adjacent liver parenchyma in 2 cases and non-selective tumor perfusion via collateral arteries in 3 cases. C-arm CT allowed sufficient visualization of uptake of lipiodol in all cases evaluated. The diagnostic benefit of C-arm CT increases if tumors are treated more selectively, are not strongly hypervascular, are located centrally and if the enhancement of liver parenchyma is inhomogeneous. C-arm CT causes additional working time and contrast load, which is relatively low compared to angiography. Radiation exposure of 151 μGy per C-arm

Microstructure and orientation evolution in unidirectional solidified Al–Zn alloys

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhongwei, E-mail: chzw@nwpu.edu.cn; Wang, Enyuan; Hao, Xiaolei

2016-06-14

Morphological instability and growth orientation evolution during unidirectional solidification of Al–Zn alloys with different pulling speeds were investigated by X-ray diffraction (XRD) and electron back-scatter diffraction (EBSD) in scanning electron microscope (SEM). The experimental results show that, as the pulling speed increases, the primary dendrite spacing becomes smaller gradually and dendrite trunks incline to the heat flow direction perfectly in unidirectional solidified Al–9.8 wt%Zn and Al–89 wt%Zn alloys. However, regardless of the pulling speed in unidirectional solidified Al–Zn alloys under fixed thermal gradient, the regular dendrites with <100> directions of primary trunks and secondary arms in 9.8 wt% Zn composition are replaced by <110> dendrites of primary trunks and secondary arms in 89 wt% Zn composition. In unidirectional solidified Al–32 wt% Zn alloy, cellular, fractal seaweed, and stabilized seaweed structures were observed at high pulling speeds. At a high pulling speed of 1000 µm/s, seaweed structures transform to the columnar dendrites with <110> trunks and <100> arms. The above orientation evolution can be attributed to low anisotropy of solid-liquid interface energy and the seaweed structure is responsible for isotropy of {111} planes.

Computer Language Choices in Arms Control and Nonproliferation Regimes

International Nuclear Information System (INIS)

White, G K

2005-01-01

The U.S. and Russian Federation continue to make substantive progress in the arms control and nonproliferation transparency regimes. We are moving toward an implementation choice for creating radiation measurement systems that are transparent in both their design and in their implementation. In particular, the choice of a programming language to write software for such regimes can decrease or significantly increase the costs of authentication. In this paper, we compare procedural languages with object-oriented languages. In particular, we examine the C and C++ languages; we compare language features, code generation, implementation details, and executable size and demonstrate how these attributes aid or hinder authentication and backdoor threats. We show that programs in lower level, procedural languages are more easily authenticated than are object-oriented ones. Potential tools and methods for authentication are covered. Possible mitigations are suggested for using object-oriented programming languages

Allosteric communication in myosin V: from small conformational changes to large directed movements.

Directory of Open Access Journals (Sweden)

M Cecchini

Full Text Available The rigor to post-rigor transition in myosin, a consequence of ATP binding, plays an essential role in the Lymn-Taylor functional cycle because it results in the dissociation of the actomyosin complex after the powerstroke. On the basis of the X-ray structures of myosin V, we have developed a new normal mode superposition model for the transition path between the two states. Rigid-body motions of the various subdomains and specific residues at the subdomain interfaces are key elements in the transition. The allosteric communication between the nucleotide binding site and the U50/L50 cleft is shown to result from local changes due to ATP binding, which induce large amplitude motions that are encoded in the structure of the protein. The triggering event is the change in the interaction of switch I and the P-loop, which is stabilized by ATP binding. The motion of switch I, which is a relatively rigid element of the U50 subdomain, leads directly to a partial opening of the U50/L50 cleft; the latter is expected to weaken the binding of myosin to actin. The calculated transition path demonstrates the nature of the subdomain coupling and offers an explanation for the mutual exclusion of ATP and actin binding. The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central beta-sheet in the rigor to post-rigor transition is described.

Myosin phosphorylation improves contractile economy of mouse fast skeletal muscle during staircase potentiation.

Science.gov (United States)

Bunda, Jordan; Gittings, William; Vandenboom, Rene

2018-01-30

Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP-requiring process. Our objective was to investigate the effect of skMLCK-catalyzed RLC phosphorylation on the energetic cost of contraction and the contractile economy (ratio of mechanical output to metabolic input) of mouse fast twitch muscle in vitro (25°C). To this end, extensor digitorum longus (EDL) muscles from wild-type (WT) and from skMLCK-devoid (skMLCK -/- ) mice were subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce staircase potentiation of isometric twitch force, after which muscles were quick frozen for determination of high-energy phosphate consumption (HEPC). During stimulation, WT muscles displayed significant potentiation of isometric twitch force while skMLCK -/- muscles did not (i.e. 23% versus 5% change, respectively). Consistent with this, RLC phosphorylation was increased ∼3.5-fold from the unstimulated control value in WT but not in skMLCK -/- muscles. Despite these differences, the HEPC of WT muscles was not greater than that of skMLCK -/- muscles. As a result of the increased contractile output relative to HEPC, the calculated contractile economy of WT muscles was greater than that of skMLCK -/- muscles. Thus, our results suggest that skMLCK-catalyzed phosphorylation of the myosin RLC increases the contractile economy of WT mouse EDL muscle compared with skMLCK -/- muscles without RLC phosphorylation. © 2018. Published by The Company of Biologists Ltd.

Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Tsuda, Takashi; Izumi, Tohru; Shibata, Akira (Niigata Univ. (Japan). School of Medicine)

1992-08-01

Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51[+-]11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of [sup 201]Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author).

Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

International Nuclear Information System (INIS)

Tsuda, Takashi; Izumi, Tohru; Shibata, Akira

1992-01-01

Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51±11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of 201 Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author)

The importance of subfragment 2 and C-terminus of myosin heavy chain for thick filament assembly in skeletal muscle cells.

Science.gov (United States)

Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Muroya, Susumu; Chikuni, Koichi; Hattori, Akihito; Nishimura, Takanori

2015-04-01

In skeletal muscle cells, myofibrillar proteins are highly organized into sarcomeres in which thick filaments interdigitate with thin filaments to generate contractile force. The size of thick filaments, which consist mainly of myosin molecules, is strictly controlled. However, little is known about the mechanisms by which myosin molecules assemble into thick filaments. Here, we assessed the ability of each domain of myosin heavy chain (Myh) to form thick filaments. We showed that exogenously expressed subfragment 2 (S2) + light meromyosin (LMM) of Myh was efficiently incorporated into thick filaments in muscle cells, although neither solely expressed S2 nor LMM targeted to thick filaments properly. In nonmuscle COS7 cells, S2+LMM formed more enlarged filaments/speckles than LMM. These results suggest that Myh filament formation is induced by S2 accompanying LMM. We further examined the effects of Myh C-terminus on thick filament assembly. C-terminal deletion mutants were incorporated not into entire thick filaments but rather into restricted regions of thick filaments. Our findings suggest that the elongation of myosin filaments to form thick filaments is regulated by S2 as well as C-terminus of LMM. © 2014 Japanese Society of Animal Science.

Mapping molecular orientational distributions for biological sample in 3D (Conference Presentation)

Science.gov (United States)

HE, Wei; Ferrand, Patrick; Richter, Benjamin; Bastmeyer, Martin; Brasselet, Sophie

2016-04-01

Measuring molecular orientation properties is very appealing for scientists in molecular and cell biology, as well as biomedical research. Orientational organization at the molecular scale is indeed an important brick to cells and tissues morphology, mechanics, functions and pathologies. Recent work has shown that polarized fluorescence imaging, based on excitation polarization tuning in the sample plane, is able to probe molecular orientational order in biological samples; however this applies only to information in 2D, projected in the sample plane. To surpass this limitation, we extended this approach to excitation polarization tuning in 3D. The principle is based on the decomposition of any arbitrary 3D linear excitation in a polarization along the longitudinal z-axis, and a polarization in the transverse xy-sample plane. We designed an interferometer with one arm generating radial polarization light (thus producing longitudinal polarization under high numerical aperture focusing), the other arm controlling a linear polarization in the transverse plane. The amplitude ratio between the two arms can vary so as to get any linear polarized excitation in 3D at the focus of a high NA objective. This technique has been characterized by polarimetry imaging at the back focal plane of the focusing objective, and modeled theoretically. 3D polarized fluorescence microscopy is demonstrated on actin stress fibers in non-flat cells suspended on synthetic polymer structures forming supporting pillars, for which heterogeneous actin orientational order could be identified. This technique shows a great potential in structural investigations in 3D biological systems, such as cell spheroids and tissues.

Construction and characterization of the alpha form of a cardiac myosin heavy chain cDNA clone and its developmental expression in the Syrian hamster.

OpenAIRE

Liew, C C; Jandreski, M A

1986-01-01

A cDNA clone, pVHC1, was isolated from a Syrian hamster heart cDNA library and was compared to the rat alpha (pCMHC21) and beta (pCMHC5) ventricular myosin heavy chain cDNA clones. The DNA sequence and amino acid sequence deducted from the DNA show more homology with pCMHC21 than pCMHC5. This indicates that pVHC1 is an alpha ventricular myosin heavy chain cDNA clone. However, even though pVHC1 shows a high degree of nucleotide and amino acid conservation with the rat myosin heavy chain sequen...

Gene transfer, expression, and sarcomeric incorporation of a headless myosin molecule in cardiac myocytes: evidence for a reserve in myofilament motor function

Science.gov (United States)

Vandenboom, Rene; Herron, Todd; Favre, Elizabeth; Albayya, Faris P.

2011-01-01

The purpose of this study was to implement a living myocyte in vitro model system to test whether a motor domain-deleted headless myosin construct could be incorporated into the sarcomere and affect contractility. To this end we used gene transfer to express a “headless” myosin heavy chain (headless-MHC) in complement with the native full-length myosin motors in the cardiac sarcomere. An NH2-terminal Flag epitope was used for unique detection of the motor domain-deleted headless-MHC. Total MHC content (i.e., headless-MHC + endogenous MHC) remained constant, while expression of the headless-MHC in transduced myocytes increased from 24 to 72 h after gene transfer until values leveled off at 96 h after gene transfer, at which time the headless-MHC comprised ∼20% of total MHC. Moreover, immunofluorescence labeling and confocal imaging confirmed expression and demonstrated incorporation of the headless-MHC in the A band of the cardiac sarcomere. Functional measurements in intact myocytes showed that headless-MHC modestly reduced amplitude of dynamic twitch contractions compared with controls (P < 0.05). In chemically permeabilized myocytes, maximum steady-state isometric force and the tension-pCa relationship were unaltered by the headless-MHC. These data suggest that headless-MHC can express to 20% of total myosin and incorporate into the sarcomere yet have modest to no effects on dynamic and steady-state contractile function. This would indicate a degree of functional tolerance in the sarcomere for nonfunctional myosin molecules. PMID:21112946

Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

Energy Technology Data Exchange (ETDEWEB)

Lima, V.V. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil); Lobato, N.S.; Filgueira, F.P. [Curso de Medicina, Setor de Fisiologia Humana, Universidade Federal de Goiás, Jataí, GO (Brazil); Webb, R.C. [Department of Physiology, Georgia Regents University, Augusta, GA (United States); Tostes, R.C. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Giachini, F.R. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil)

2014-08-15

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca{sup 2+}/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

Nuclear myosin is ubiquitously expressed and evolutionary conserved in vertebrates

Czech Academy of Sciences Publication Activity Database

Kahle, Michal; Přidalová, Jarmila; Špaček, M.; Dzijak, Rastislav; Hozák, Pavel

2007-01-01

Roč. 127, č. 2 (2007), s. 139-184 ISSN 0948-6143 R&D Projects: GA ČR GA204/04/0108; GA AV ČR IAA5039202; GA MŠk LC545; GA ČR GD204/05/H023 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50520514 Keywords : Nuclear myosin I * Transcription * Chromatin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.893, year: 2007

Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task.

Directory of Open Access Journals (Sweden)

Kazuyoshi Kigawa

Full Text Available Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant's view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70-80 Hz vibration to the elbow flexors of the reference arm (= right arm to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another.

A novel de novo mutation of β-cardiac myosin heavy chain gene ...

Indian Academy of Sciences (India)

2014-08-18

Aug 18, 2014 ... It is one of the most important diseases causing a sud- den death in ... familial HCM encode contractile proteins such as β-cardiac myosin ... A previously healthy 12-year-old boy was admitted to our hospital for .... Maron B. J. 2002 Hypertrophic cardiomyopathy: A systematic review. JAMA 287, 1308–1320.

Sarcomere lattice geometry influences cooperative myosin binding in muscle.

Directory of Open Access Journals (Sweden)

Bertrand C W Tanner

2007-07-01

Full Text Available In muscle, force emerges from myosin binding with actin (forming a cross-bridge. This actomyosin binding depends upon myofilament geometry, kinetics of thin-filament Ca(2+ activation, and kinetics of cross-bridge cycling. Binding occurs within a compliant network of protein filaments where there is mechanical coupling between myosins along the thick-filament backbone and between actin monomers along the thin filament. Such mechanical coupling precludes using ordinary differential equation models when examining the effects of lattice geometry, kinetics, or compliance on force production. This study uses two stochastically driven, spatially explicit models to predict levels of cross-bridge binding, force, thin-filament Ca(2+ activation, and ATP utilization. One model incorporates the 2-to-1 ratio of thin to thick filaments of vertebrate striated muscle (multi-filament model, while the other comprises only one thick and one thin filament (two-filament model. Simulations comparing these models show that the multi-filament predictions of force, fractional cross-bridge binding, and cross-bridge turnover are more consistent with published experimental values. Furthermore, the values predicted by the multi-filament model are greater than those values predicted by the two-filament model. These increases are larger than the relative increase of potential inter-filament interactions in the multi-filament model versus the two-filament model. This amplification of coordinated cross-bridge binding and cycling indicates a mechanism of cooperativity that depends on sarcomere lattice geometry, specifically the ratio and arrangement of myofilaments.

Long range position and orientation tracking system

International Nuclear Information System (INIS)

Armstrong, G.A.; Jansen, J.F.; Burks, B.L.; Bernacki, B.E.; Nypaver, D.J.

1995-01-01

The long range position and orientation tracking system (LRPOTS) will consist of two measurement pods, a VME-based computer system, and a detector array. The system is used to measure the position and orientation of a target that may be attached to a robotic arm, teleoperated manipulator, or autonomous vehicle. The pods have been designed to be mounted in the man-ways of the domes of the Fernald K-65 waste silos. Each pod has two laser scanner subsystems as well as lights and camera systems. One of the laser scanners will be oriented to scan in the pan direction, the other in the tilt direction. As the lasers scan across the detector array, the angles of incidence with each detector are recorded. Combining measurements from each of the four lasers yields sufficient data for a closed-form solution of the transform describing the location and orientation of the Content Mobilization System (CMS). Redundant detectors will be placed on the CMS to accommodate occlusions, to provide improved measurement accuracy, and to determine the CMS orientation

Long-range position and orientation tracking system

International Nuclear Information System (INIS)

Armstrong, G.A.; Jansen, J.F.; Burks, B.L.

1995-01-01

The long-range position and orientation tracking system will consist of two measurement pods, a VME-based computer system, and a detector array. The system is used to measure the position and orientation of a target that may be attached to a robotic arm, teleoperated manipulator, or autonomous vehicle. The pods have been designed to be mounted in the manways of the domes of the Fernald K-65 waste silos. Each pod has two laser scanner subsystems as well as lights and camera systems. One of the laser scanners will be oriented to scan in the pan direction, the other in the tilt direction. As the lasers scan across the detector array, the angles of incidence with each detector are recorded. Combining measurements from each of the four lasers yields sufficient data for a closed-form solution of the transform describing the location and orientation of the content mobilization system (CMS). Redundant detectors will be placed on the CMS to accommodate occlusions, to provide improved measurement accuracy, and to determine the CMS orientation

Intuitive adaptive orientation control of assistive robots for people living with upper limb disabilities.

Science.gov (United States)

Vu, Dinh-Son; Allard, Ulysse Cote; Gosselin, Clement; Routhier, Francois; Gosselin, Benoit; Campeau-Lecours, Alexandre

2017-07-01

Robotic assistive devices enhance the autonomy of individuals living with physical disabilities in their day-to-day life. Although the first priority for such devices is safety, they must also be intuitive and efficient from an engineering point of view in order to be adopted by a broad range of users. This is especially true for assistive robotic arms, as they are used for the complex control tasks of daily living. One challenge in the control of such assistive robots is the management of the end-effector orientation which is not always intuitive for the human operator, especially for neophytes. This paper presents a novel orientation control algorithm designed for robotic arms in the context of human-robot interaction. This work aims at making the control of the robot's orientation easier and more intuitive for the user, in particular, individuals living with upper limb disabilities. The performance and intuitiveness of the proposed orientation control algorithm is assessed through two experiments with 25 able-bodied subjects and shown to significantly improve on both aspects.

Single-molecule imaging reveals topological isomer-dependent diffusion by 4-armed star and dicyclic 8-shaped polymers

KAUST Repository

Habuchi, Satoshi

2015-04-21

Diffusion dynamics of topological isomers of polymer molecules was investigated at the single-molecule level in a melt state by employing the fluorophore-incorporated 4-armed star and the corresponding doubly-cyclized, 8-shaped poly(THF) chains. While the single-molecule fluorescence imaging experiment revealed that the diffusion of the 4-armed star polymer was described by a single Gaussian distribution, the diffusion of the 8-shaped polymer exhibited a double Gaussian distribution behaviour. We reasoned that the two 8-shaped polymeric isomers have distinct diffusion modes in the melt state, although ensemble-averaged experimental methods cannot detect differences in overall conformational state of the isomers. The single-molecule experiments suggested that one of the 8-shaped polymeric isomer, having the horizontally oriented form, causes an efficient threading with the linear matrix chains which leads to the slower diffusion compared with the corresponding 4-armed star polymer, while the other 8-shaped polymeric isomer, having the vertically oriented form, displayed faster diffusion by the suppression of effective threading with the linear matrix chains due to its contracted chain conformation.

Individualized tracking of self-directed motor learning in group-housed mice performing a skilled lever positioning task in the home cage.

Science.gov (United States)

Silasi, Gergely; Boyd, Jamie D; Bolanos, Federico; LeDue, Jeff M; Scott, Stephen H; Murphy, Timothy H

2018-01-01

Skilled forelimb function in mice is traditionally studied through behavioral paradigms that require extensive training by investigators and are limited by the number of trials individual animals are able to perform within a supervised session. We developed a skilled lever positioning task that mice can perform within their home cage. The task requires mice to use their forelimb to precisely hold a lever mounted on a rotary encoder within a rewarded position to dispense a water reward. A Raspberry Pi microcomputer is used to record lever position during trials and to control task parameters, thus making this low-footprint apparatus ideal for use within animal housing facilities. Custom Python software automatically increments task difficulty by requiring a longer hold duration, or a more accurate hold position, to dispense a reward. The performance of individual animals within group-housed mice is tracked through radio-frequency identification implants, and data stored on the microcomputer may be accessed remotely through an active internet connection. Mice continuously engage in the task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials to learn to hold the lever within a 10° range for 1.5 s and were able to further refine movement accuracy by limiting their error to a 5° range within each trial. These results demonstrate the feasibility of autonomously training group-housed mice on a forelimb motor task. This paradigm may be used in the future to assess functional recovery after injury or cortical reorganization induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost system for fully autonomous training of group-housed mice on a forelimb motor task. We demonstrate the feasibility of tracking both end-point, as well as kinematic performance of individual mice, with each performing thousands of trials over 2.5 mo. The task is run and controlled by a Raspberry Pi microcomputer, which allows for cages to be

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11)

NARCIS (Netherlands)

Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

2004-01-01

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).

NARCIS (Netherlands)

Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

2004-01-01

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

Robotic arm

Science.gov (United States)

Kwech, Horst

1989-04-18

A robotic arm positionable within a nuclear vessel by access through a small diameter opening and having a mounting tube supported within the vessel and mounting a plurality of arm sections for movement lengthwise of the mounting tube as well as for movement out of a window provided in the wall of the mounting tube. An end effector, such as a grinding head or welding element, at an operating end of the robotic arm, can be located and operated within the nuclear vessel through movement derived from six different axes of motion provided by mounting and drive connections between arm sections of the robotic arm. The movements are achieved by operation of remotely-controllable servo motors, all of which are mounted at a control end of the robotic arm to be outside the nuclear vessel.

Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation

Directory of Open Access Journals (Sweden)

Kate Fisher

2013-10-01

Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin.

Design considerations in coiled-coil fusion constructs for the structural determination of a problematic region of the human cardiac myosin rod

Energy Technology Data Exchange (ETDEWEB)

Andreas, Michael P.; Ajay, Gautam; Gellings, Jaclyn A.; Rayment, Ivan (UW)

2017-12-01

X-ray structural determination of segments of the myosin rod has proved difficult because of the strong salt-dependent aggregation properties and repeating pattern of charges on the surface of the coiled-coil that lead to the formation of paracrystals. This problem has been resolved in part through the use of globular assembly domains that improve protein folding and prevent aggregation. The primary consideration now in designing coiled-coil fusion constructs for myosin is deciding where to truncate the coiled-coil and which amino acid residues to include from the folding domain. This is especially important for myosin that contains numerous regions of low predicted coiled-coil propensity. Here we describe the strategy adopted to determine the structure of the region that extends from Arg1677 – Leu1797 that included two areas that do not show a strong sequence signature of a conventional left-handed coiled coil or canonical heptad repeat. This demonstrates again that, with careful choice of fusion constructs, overlapping structures exhibit very similar conformations for the myosin rod fragments in the canonical regions. However, conformational variability is seen around Leu1706 which is a hot spot for cardiomyopathy mutations suggesting that this might be important for function.

Combined Influence of Visual Scene and Body Tilt on Arm Pointing Movements: Gravity Matters!

Science.gov (United States)

Scotto Di Cesare, Cécile; Sarlegna, Fabrice R.; Bourdin, Christophe; Mestre, Daniel R.; Bringoux, Lionel

2014-01-01

Performing accurate actions such as goal-directed arm movements requires taking into account visual and body orientation cues to localize the target in space and produce appropriate reaching motor commands. We experimentally tilted the body and/or the visual scene to investigate how visual and body orientation cues are combined for the control of unseen arm movements. Subjects were asked to point toward a visual target using an upward movement during slow body and/or visual scene tilts. When the scene was tilted, final pointing errors varied as a function of the direction of the scene tilt (forward or backward). Actual forward body tilt resulted in systematic target undershoots, suggesting that the brain may have overcompensated for the biomechanical movement facilitation arising from body tilt. Combined body and visual scene tilts also affected final pointing errors according to the orientation of the visual scene. The data were further analysed using either a body-centered or a gravity-centered reference frame to encode visual scene orientation with simple additive models (i.e., ‘combined’ tilts equal to the sum of ‘single’ tilts). We found that the body-centered model could account only for some of the data regarding kinematic parameters and final errors. In contrast, the gravity-centered modeling in which the body and visual scene orientations were referred to vertical could explain all of these data. Therefore, our findings suggest that the brain uses gravity, thanks to its invariant properties, as a reference for the combination of visual and non-visual cues. PMID:24925371

Robotic arm

International Nuclear Information System (INIS)

Kwech, H.

1989-01-01

A robotic arm positionable within a nuclear vessel by access through a small diameter opening and having a mounting tube supported within the vessel and mounting a plurality of arm sections for movement lengthwise of the mounting tube as well as for movement out of a window provided in the wall of the mounting tube is disclosed. An end effector, such as a grinding head or welding element, at an operating end of the robotic arm, can be located and operated within the nuclear vessel through movement derived from six different axes of motion provided by mounting and drive connections between arm sections of the robotic arm. The movements are achieved by operation of remotely-controllable servo motors, all of which are mounted at a control end of the robotic arm to be outside the nuclear vessel. 23 figs

Estimation of Human Arm Joints Using Two Wireless Sensors in Robotic Rehabilitation Tasks

Directory of Open Access Journals (Sweden)

Arturo Bertomeu-Motos

2015-12-01

Full Text Available This paper presents a novel kinematic reconstruction of the human arm chain with five degrees of freedom and the estimation of the shoulder location during rehabilitation therapy assisted by end-effector robotic devices. This algorithm is based on the pseudoinverse of the Jacobian through the acceleration of the upper arm, measured using an accelerometer, and the orientation of the shoulder, estimated with a magnetic angular rate and gravity (MARG device. The results show a high accuracy in terms of arm joints and shoulder movement with respect to the real arm measured through an optoelectronic system. Furthermore, the range of motion (ROM of 50 healthy subjects is studied from two different trials, one trying to avoid shoulder movements and the second one forcing them. Moreover, the shoulder movement in the second trial is also estimated accurately. Besides the fact that the posture of the patient can be corrected during the exercise, the therapist could use the presented algorithm as an objective assessment tool. In conclusion, the joints’ estimation enables a better adjustment of the therapy, taking into account the needs of the patient, and consequently, the arm motion improves faster.

Interactive Design and Development of Real Arm Movements for Application in Rehabilitation

Science.gov (United States)

Rosman, Rafidah; Hadi, Muhammad Zaidan Abdul; Abu Bakar, Nurulliyana

2018-03-01

An interactive real arm movements for application in rehabilitation is designed and developed. The aim is to encourage hand paralysis patients performing their physical therapy by introducing games application in replacing conventional hand therapy module and methods. In this project, the accelerometer is used for tracking the orientation of the arm. As the arm moves, the values from x, y and z axis from the accelerometer changes and are being read by the Analog Inputs of the Arduino Board. After being read by the Analog Inputs of the Arduino Board, the 3D model moves as well. Solidworks software was used to modeled the hand in which the data is then transferred to Matlab/Simulink using SimMechanicalLink from Mathworks. Lastly, the sensor glove was programmed to work as a controller of games application in hand rehabilitation thus makes it an enjoyable therapy process.

The local expression of adult chicken heart myosins during development. II. Ventricular conducting tissue

NARCIS (Netherlands)

Sanders, E.; de Groot, I. J.; Geerts, W. J.; de Jong, F.; van Horssen, A. A.; Los, J. A.; Moorman, A. F.

1986-01-01

The development of the ventricular conducting tissue of the embryonic chicken heart has been studied using a previous finding that morphologically recognizable atrial conducting tissue coexpresses the atrial and the ventricular myosin isoforms. It is found that, by these criteria, at 9 days part of

Physiological and subjective measures of workload when shovelling with a conventional and two-handled ('levered') shovel.

Science.gov (United States)

Bridger, R S; Cabion, N; Goedecke, J; Rickard, S; Schabort, E; Westgarth-Taylor, C; Lambert, M I

1997-11-01

Previous studies have suggested that the two-handled (levered) shovel is advantageous over the conventional spade from a biomechanical point of view. The aim of this experiment was to determine whether less energy was consumed while shovelling a load of sand with this shovel compared to a conventional tool. Accordingly, an experiment was designed in which subjects (n = 10) shovelled 1815 kg sand under laboratory conditions using either a conventional or a levered shovel. Heart rate and oxygen consumption were measured continuously during the trial and subjective data on perceived exertion, general fatigue and body discomfort were recorded after the trial. Although total energy expenditure was similar under both conditions (120 +/- 20 and 125 +/- 25 kcal; conventional versus two-handled spade), average heart rate was 4% higher when the two-handled shovel was used (p shovel (p shovel 1815 kg sand with the conventional shovel and the two-handled tool despite lower mass of sand per scoop with the latter. This can be explained by the fact that the increased mass of the additional handle compensated for the lower mass of sand per scoop. The higher average heart rate while shovelling with the two-handled shovel can be explained by the more erect posture.

The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

Science.gov (United States)

Fang, Qing; Indzhykulian, Artur A; Mustapha, Mirna; Riordan, Gavin P; Dolan, David F; Friedman, Thomas B; Belyantseva, Inna A; Frolenkov, Gregory I; Camper, Sally A; Bird, Jonathan E

2015-01-01

The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, a critical subset of stereocilia with active mechanotransducer channels subsequently retracts. The larger isoform with the 133-kDa N-terminal domain traffics to these specialized stereocilia and prevents disassembly of their actin core. Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture. DOI: http://dx.doi.org/10.7554/eLife.08627.001 PMID:26302205

Tactics at the category level of purchasing and supply management: sourcing levers, contingencies and performance

OpenAIRE

Hesping, Frank

2015-01-01

For the ‘front-line’ purchasing agent, it is obvious that not all categories of products and supplier relationships should be managed in the same way. Rather, in a modern category management approach, firms group similar products into ‘sourcing categories’ forming coherent supply markets (e.g., ‘metal sheets’, ‘leather’, ‘displays’, ‘cables’, etc.). Thus, to achieve cost reduction targets, a tailored mix of tactical sourcing levers for each sourcing category may be required. The fundamental q...

A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads.

Science.gov (United States)

Iwaki, M; Wickham, S F; Ikezaki, K; Yanagida, T; Shih, W M

2016-12-12

Mechanosensitive biological nanomachines such as motor proteins and ion channels regulate diverse cellular behaviour. Combined optical trapping with single-molecule fluorescence imaging provides a powerful methodology to clearly characterize the mechanoresponse, structural dynamics and stability of such nanomachines. However, this system requires complicated experimental geometry, preparation and optics, and is limited by low data-acquisition efficiency. Here we develop a programmable DNA origami nanospring that overcomes these issues. We apply our nanospring to human myosin VI, a mechanosensory motor protein, and demonstrate nanometre-precision single-molecule fluorescence imaging of the individual motor domains (heads) under force. We observe force-induced transitions of myosin VI heads from non-adjacent to adjacent binding, which correspond to adapted roles for low-load and high-load transport, respectively. Our technique extends single-molecule studies under force and clarifies the effect of force on biological processes.

Expression of smooth muscle and non-muscle myosin heavy chain isoforms in cultured vascular smooth muscle cells

International Nuclear Information System (INIS)

Rovner, A.S.; Murphy, R.A.; Owens, G.K.

1986-01-01

Immunocytochemical studies of cultured smooth muscle cells (SMCs) have disagreed on the nature of myosin expression. This investigation was undertaken to test for the presence of heterogeneous myosin heavy chain (MHC) isoforms in cell culture as a possible explanation for these results. Previously, Rovner et al. detected two MHCs in intact smooth muscles which differed in molecular weight by ca. 4000 daltons (SM1 and SM2) using a 3-4% acrylamide gradient SDS gel system. When sub-confluent primary cultures of rat aorta SMCs were assayed by this system, SM1 and SM2 were seen, along with large amounts of a third, unique MHC, NM, which closely resembled the MHC from human platelet in size and antigenicity. Data from 35 S-methionine autoradiograms showed that the log growth phase SMC cultures were producing almost exclusively NM, but the growth arrest, post-confluent cultures synthesized increased relative amounts of the SM MHC forms and contained comparable amounts of SM1, SM2, and NM. The same patterns of MHC synthesis were seen in sub-passaged SMCs. The expression of the SM-specific forms of myosin in quiescent, post-confluent cultures parallels that of smooth muscle actin suggesting that density induced growth arrest promotes cytodifferentiation in cultured vascular SMCs

Exact positioning of the robotic arm end effector

Science.gov (United States)

Korepanov, Valery; Dudkin, Fedir

2016-07-01

Orbital service becomes a new challenge of space exploration. The necessity to introduce it is connected first of all with an attractive opportunity to prolong the exploitation terms of expensive commercial satellites by, e.g., refilling of fuel or changing batteries. Other application area is a fight with permanently increasing amount of space litter - defunct satellites, burnt-out rocket stages, discarded trash and other debris. Now more than few tens of thousands orbiting objects larger than 5-10 cm (or about 1 million junks larger than 1 cm) are a huge problem for crucial and costly satellites and manned vehicles. For example, in 2014 the International Space Station had to change three times its orbit to avoid collision with space debris. So the development of the concepts and actions related to removal of space debris or non-operational satellites with use of robotic arm of a servicing satellite is very actual. Such a technology is also applicable for unmanned exploratory missions in solar system, for example for collecting a variety of samples from a celestial body surface. Naturally, the robotic arm movements should be controlled with great accuracy at influence of its non-rigidity, thermal and other factors. In these circumstances often the position of the arm end effector has to be controlled with high accuracy. The possibility of coordinate determination for the robotic arm end effector with use of a low frequency active electromagnetic system has been considered in the presented report. The proposed design of such a system consists of a small magnetic dipole source, which is mounted inside of the arm end effector and two or three 3-component magnetic field sensors mounted on a servicing satellite body. The data from this set of 3-component magnetic field sensors, which are fixed relatively to the satellite body, allows use of the mathematical approach for determination of position and orientation of the magnetic dipole source. The theoretical

The IQ motif drives the nuclear translocation of nuclear myosin I

Czech Academy of Sciences Publication Activity Database

Dzijak, Rastislav; Yildirim, Sukriye; Kahle, Michal; Hozák, Pavel

2008-01-01

Roč. 275, č. 1 (2008), s. 67-67 E-ISSN 1742-4658. [FEBS Congress /33rd/, IUBMB conference /11th/. 28.06.2008-03.07.2008, Athens] R&D Projects: GA MŠk LC545; GA ČR(CZ) GA204/07/1592 Grant - others:GAČR(CZ) GD204/05/H023 Program:GD Institutional research plan: CEZ:AV0Z50520514 Keywords : nuclear myosin * nuclear transport Subject RIV: EB - Genetics ; Molecular Biology

The spiral arms of the Milky Way: The relative location of each different arm tracer within a typical spiral arm width

Energy Technology Data Exchange (ETDEWEB)

Vallée, Jacques P., E-mail: jacques.vallee@nrc-cnrc.gc.ca [National Research Council Canada, National Science Infrastructure portfolio, Herzberg Astronomy and Astrophysics, 5071 West Saanich Road, Victoria, B.C., V9E 2E7 (Canada)

2014-07-01

From the Sun's location in the Galactic disk, different arm tracers (CO, H I, hot dust, etc.) have been employed to locate a tangent to each spiral arm. Using all various and different observed spiral arm tracers (as published elsewhere), we embark on a new goal, namely the statistical analysis of these published data (data mining) to statistically compute the mean location of each spiral arm tracer. We show for a typical arm cross-cut, a separation of 400 pc between the mid-arm and the dust lane (at the inner edge of the arm, toward the Galactic center). Are some arms major and others minor? Separating arms into two sets, as suggested by some, we find the same arm widths between the two sets. Our interpretation is that we live in a multiple (four-arm) spiral (logarithmic) pattern (around a pitch angle of 12°) for the stars and gas in the Milky Way, with a sizable interarm separation (around 3 kpc) at the Sun's location and the same arm width for each arm (near 400 pc from mid-arm to dust lane).

The spiral arms of the Milky Way: The relative location of each different arm tracer within a typical spiral arm width

International Nuclear Information System (INIS)

Vallée, Jacques P.

2014-01-01

From the Sun's location in the Galactic disk, different arm tracers (CO, H I, hot dust, etc.) have been employed to locate a tangent to each spiral arm. Using all various and different observed spiral arm tracers (as published elsewhere), we embark on a new goal, namely the statistical analysis of these published data (data mining) to statistically compute the mean location of each spiral arm tracer. We show for a typical arm cross-cut, a separation of 400 pc between the mid-arm and the dust lane (at the inner edge of the arm, toward the Galactic center). Are some arms major and others minor? Separating arms into two sets, as suggested by some, we find the same arm widths between the two sets. Our interpretation is that we live in a multiple (four-arm) spiral (logarithmic) pattern (around a pitch angle of 12°) for the stars and gas in the Milky Way, with a sizable interarm separation (around 3 kpc) at the Sun's location and the same arm width for each arm (near 400 pc from mid-arm to dust lane).

Technetium-99m labeling of antibodies to cardiac myosin Fab and to human fibrinogen

International Nuclear Information System (INIS)

Khaw, B.A.; Strauss, H.W.; Carvalho, A.; Locke, E.; Gold, H.K.; Haber, E.

1982-01-01

A method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with Tc-99m at neutral pH was developed. This method uses dithionite reduction of pertechnetate and subsequent labeling to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the Tc-99m D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80-88% coagulable. The Tc-99m AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the Tc-99m labeling of other biologically active and acid-labile macromolecules

Clot retraction is mediated by factor XIII-dependent fibrin-αIIbβ3-myosin axis in platelet sphingomyelin-rich membrane rafts.

Science.gov (United States)

Kasahara, Kohji; Kaneda, Mizuho; Miki, Toshiaki; Iida, Kazuko; Sekino-Suzuki, Naoko; Kawashima, Ikuo; Suzuki, Hidenori; Shimonaka, Motoyuki; Arai, Morio; Ohno-Iwashita, Yoshiko; Kojima, Soichi; Abe, Mitsuhiro; Kobayashi, Toshihide; Okazaki, Toshiro; Souri, Masayoshi; Ichinose, Akitada; Yamamoto, Naomasa

2013-11-07

Membrane rafts are spatially and functionally heterogenous in the cell membrane. We observed that lysenin-positive sphingomyelin (SM)-rich rafts are identified histochemically in the central region of adhered platelets where fibrin and myosin are colocalized on activation by thrombin. The clot retraction of SM-depleted platelets from SM synthase knockout mouse was delayed significantly, suggesting that platelet SM-rich rafts are involved in clot retraction. We found that fibrin converted by thrombin translocated immediately in platelet detergent-resistant membrane (DRM) rafts but that from Glanzmann's thrombasthenic platelets failed. The fibrinogen γ-chain C-terminal (residues 144-411) fusion protein translocated to platelet DRM rafts on thrombin activation, but its mutant that was replaced by A398A399 at factor XIII crosslinking sites (Q398Q399) was inhibited. Furthermore, fibrin translocation to DRM rafts was impaired in factor XIII A subunit-deficient mouse platelets, which show impaired clot retraction. In the cytoplasm, myosin translocated concomitantly with fibrin translocation into the DRM raft of thrombin-stimulated platelets. Furthermore, the disruption of SM-rich rafts by methyl-β-cyclodextrin impaired myosin activation and clot retraction. Thus, we propose that clot retraction takes place in SM-rich rafts where a fibrin-αIIbβ3-myosin complex is formed as a primary axis to promote platelet contraction.

Dynamic model of the octopus arm. I. Biomechanics of the octopus reaching movement.

Science.gov (United States)

Yekutieli, Yoram; Sagiv-Zohar, Roni; Aharonov, Ranit; Engel, Yaakov; Hochner, Binyamin; Flash, Tamar

2005-08-01

The octopus arm requires special motor control schemes because it consists almost entirely of muscles and lacks a rigid skeletal support. Here we present a 2D dynamic model of the octopus arm to explore possible strategies of movement control in this muscular hydrostat. The arm is modeled as a multisegment structure, each segment containing longitudinal and transverse muscles and maintaining a constant volume, a prominent feature of muscular hydrostats. The input to the model is the degree of activation of each of its muscles. The model includes the external forces of gravity, buoyancy, and water drag forces (experimentally estimated here). It also includes the internal forces generated by the arm muscles and the forces responsible for maintaining a constant volume. Using this dynamic model to investigate the octopus reaching movement and to explore the mechanisms of bend propagation that characterize this movement, we found the following. 1) A simple command producing a wave of muscle activation moving at a constant velocity is sufficient to replicate the natural reaching movements with similar kinematic features. 2) The biomechanical mechanism that produces the reaching movement is a stiffening wave of muscle contraction that pushes a bend forward along the arm. 3) The perpendicular drag coefficient for an octopus arm is nearly 50 times larger than the tangential drag coefficient. During a reaching movement, only a small portion of the arm is oriented perpendicular to the direction of movement, thus minimizing the drag force.

Specific nuclear localizing sequence directs two myosin isoforms to the cell nucleus in calmodulin-sensitive manner.

Science.gov (United States)

Dzijak, Rastislav; Yildirim, Sukriye; Kahle, Michal; Novák, Petr; Hnilicová, Jarmila; Venit, Tomáš; Hozák, Pavel

2012-01-01

Nuclear myosin I (NM1) was the first molecular motor identified in the cell nucleus. Together with nuclear actin, they participate in crucial nuclear events such as transcription, chromatin movements, and chromatin remodeling. NM1 is an isoform of myosin 1c (Myo1c) that was identified earlier and is known to act in the cytoplasm. NM1 differs from the "cytoplasmic" myosin 1c only by additional 16 amino acids at the N-terminus of the molecule. This amino acid stretch was therefore suggested to direct NM1 into the nucleus. We investigated the mechanism of nuclear import of NM1 in detail. Using over-expressed GFP chimeras encoding for truncated NM1 mutants, we identified a specific sequence that is necessary for its import to the nucleus. This novel nuclear localization sequence is placed within calmodulin-binding motif of NM1, thus it is present also in the Myo1c. We confirmed the presence of both isoforms in the nucleus by transfection of tagged NM1 and Myo1c constructs into cultured cells, and also by showing the presence of the endogenous Myo1c in purified nuclei of cells derived from knock-out mice lacking NM1. Using pull-down and co-immunoprecipitation assays we identified importin beta, importin 5 and importin 7 as nuclear transport receptors that bind NM1. Since the NLS sequence of NM1 lies within the region that also binds calmodulin we tested the influence of calmodulin on the localization of NM1. The presence of elevated levels of calmodulin interfered with nuclear localization of tagged NM1. We have shown that the novel specific NLS brings to the cell nucleus not only the "nuclear" isoform of myosin I (NM1 protein) but also its "cytoplasmic" isoform (Myo1c protein). This opens a new field for exploring functions of this molecular motor in nuclear processes, and for exploring the signals between cytoplasm and the nucleus.

Biomechanics of the natural, arthritic, and replaced human ankle joint

Science.gov (United States)

2014-01-01

The human ankle joint complex plays a fundamental role in gait and other activities of daily living. At the same time, it is a very complicated anatomical system but the large literature of experimental and modelling studies has not fully described the coupled joint motion, position and orientation of the joint axis of rotation, stress and strain in the ligaments and their role in guiding and stabilizing joint motion, conformity and congruence of the articular surfaces, patterns of contact at the articular surfaces, patterns of rolling and sliding at the joint surfaces, and muscle lever arm lengths. The present review article addresses these issues as described in the literature, reporting the most recent relevant findings. PMID:24499639

The Microsoft Visual Studio Software Development For 5 DOF Nuclear Malaysia Robot Arm V2 Control System

International Nuclear Information System (INIS)

Mohd Zaid Hassan; Anwar Abdul Rahman; Azraf Azman; Mohd Rizal Mamat; Mohd Arif Hamzah

2014-01-01

This paper presents the Microsoft visual studio development for 5DOF Nuclear Malaysia Robot Arm V2 control system. The kinematics analysis is the study of the relationship between the individual joints of robot manipulator, the position and orientation of the end-effector. The Denavit-Hartenberg (DH) model is used to model the robot links and joints. Both forward and inverse kinematic are presented. The simulation software has been developed by using Microsoft visual studio to solve the robot arms kinematic behavior. (author)

Isotropy of an Upper Limb Exoskeleton and the Kinematics and Dynamics of the Human Arm

Directory of Open Access Journals (Sweden)

Joel C. Perry

2009-01-01

shoulder and elbow, and nearly half of the total torque at the wrist. These results suggest that the majority of human arm joint torques are devoted to supporting the human arm position in space while compensating gravitational loads whereas a minor portion of the joint torques is dedicated to arm motion itself. A unique axial orientation at the base of the exoskeleton allowed the singular configuration of the shoulder joint to be moved towards the boundary of the human arm workspace while supporting 95% of the arm's workspace. At the same time, this orientation allowed the best exoskeleton manipulability at the most commonly used human arm configuration during ADLs. One of the potential implications of these results might be the need to compensate gravitational load during robotic-assistive rehabilitation treatment. Moreover, results of a manipulability analysis of the exoskeleton system indicate that the singular configuration of the exoskeleton system may be moved out of the human arm physiological workspace while maximising the overlap between the human arm and the exoskeleton workspaces. The collected database along with kinematic and dynamic analyses may provide a fundamental basis towards the development of assistive technologies for the human arm.

Myosin II Motor Activity in the Lateral Amygdala Is Required for Fear Memory Consolidation

Science.gov (United States)

Gavin, Cristin F.; Rubio, Maria D.; Young, Erica; Miller, Courtney; Rumbaugh, Gavin

2012-01-01

Learning induces dynamic changes to the actin cytoskeleton that are required to support memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during learning and memory are poorly understood. Myosin II motors are highly expressed in actin-rich growth structures including dendritic spines, and we have…

Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.

Science.gov (United States)

Green, Judith L; Wall, Richard J; Vahokoski, Juha; Yusuf, Noor A; Ridzuan, Mohd A Mohd; Stanway, Rebecca R; Stock, Jessica; Knuepfer, Ellen; Brady, Declan; Martin, Stephen R; Howell, Steven A; Pires, Isa P; Moon, Robert W; Molloy, Justin E; Kursula, Inari; Tewari, Rita; Holder, Anthony A

2017-10-27

Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain-interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Evolution of robotic arms.

Science.gov (United States)

Moran, Michael E

2007-01-01

The foundation of surgical robotics is in the development of the robotic arm. This is a thorough review of the literature on the nature and development of this device with emphasis on surgical applications. We have reviewed the published literature and classified robotic arms by their application: show, industrial application, medical application, etc. There is a definite trend in the manufacture of robotic arms toward more dextrous devices, more degrees-of-freedom, and capabilities beyond the human arm. da Vinci designed the first sophisticated robotic arm in 1495 with four degrees-of-freedom and an analog on-board controller supplying power and programmability. von Kemplen's chess-playing automaton left arm was quite sophisticated. Unimate introduced the first industrial robotic arm in 1961, it has subsequently evolved into the PUMA arm. In 1963 the Rancho arm was designed; Minsky's Tentacle arm appeared in 1968, Scheinman's Stanford arm in 1969, and MIT's Silver arm in 1974. Aird became the first cyborg human with a robotic arm in 1993. In 2000 Miguel Nicolalis redefined possible man-machine capacity in his work on cerebral implantation in owl-monkeys directly interfacing with robotic arms both locally and at a distance. The robotic arm is the end-effector of robotic systems and currently is the hallmark feature of the da Vinci Surgical System making its entrance into surgical application. But, despite the potential advantages of this computer-controlled master-slave system, robotic arms have definite limitations. Ongoing work in robotics has many potential solutions to the drawbacks of current robotic surgical systems.

Comparative genomic analysis of the arthropod muscle myosin heavy chain genes allows ancestral gene reconstruction and reveals a new type of 'partially' processed pseudogene

Directory of Open Access Journals (Sweden)

Kollmar Martin

2008-02-01

Full Text Available Abstract Background Alternative splicing of mutually exclusive exons is an important mechanism for increasing protein diversity in eukaryotes. The insect Mhc (myosin heavy chain gene produces all different muscle myosins as a result of alternative splicing in contrast to most other organisms of the Metazoa lineage, that have a family of muscle genes with each gene coding for a protein specialized for a functional niche. Results The muscle myosin heavy chain genes of 22 species of the Arthropoda ranging from the waterflea to wasp and Drosophila have been annotated. The analysis of the gene structures allowed the reconstruction of an ancient muscle myosin heavy chain gene and showed that during evolution of the arthropods introns have mainly been lost in these genes although intron gain might have happened in a few cases. Surprisingly, the genome of Aedes aegypti contains another and that of Culex pipiens quinquefasciatus two further muscle myosin heavy chain genes, called Mhc3 and Mhc4, that contain only one variant of the corresponding alternative exons of the Mhc1 gene. Mhc3 transcription in Aedes aegypti is documented by EST data. Mhc3 and Mhc4 inserted in the Aedes and Culex genomes either by gene duplication followed by the loss of all but one variant of the alternative exons, or by incorporation of a transcript of which all other variants have been spliced out retaining the exon-intron structure. The second and more likely possibility represents a new type of a 'partially' processed pseudogene. Conclusion Based on the comparative genomic analysis of the alternatively spliced arthropod muscle myosin heavy chain genes we propose that the splicing process operates sequentially on the transcript. The process consists of the splicing of the mutually exclusive exons until one exon out of the cluster remains while retaining surrounding intronic sequence. In a second step splicing of introns takes place. A related mechanism could be responsible for

Feedforward compensation for novel dynamics depends on force field orientation but is similar for the left and right arms.

Science.gov (United States)

Reuter, Eva-Maria; Cunnington, Ross; Mattingley, Jason B; Riek, Stephan; Carroll, Timothy J

2016-11-01

There are well-documented differences in the way that people typically perform identical motor tasks with their dominant and the nondominant arms. According to Yadav and Sainburg's (Neuroscience 196: 153-167, 2011) hybrid-control model, this is because the two arms rely to different degrees on impedance control versus predictive control processes. Here, we assessed whether differences in limb control mechanisms influence the rate of feedforward compensation to a novel dynamic environment. Seventy-five healthy, right-handed participants, divided into four subsamples depending on the arm (left, right) and direction of the force field (ipsilateral, contralateral), reached to central targets in velocity-dependent curl force fields. We assessed the rate at which participants developed predictive compensation for the force field using intermittent error-clamp trials and assessed both kinematic errors and initial aiming angles in the field trials. Participants who were exposed to fields that pushed the limb toward ipsilateral space reduced kinematic errors more slowly, built up less predictive field compensation, and relied more on strategic reaiming than those exposed to contralateral fields. However, there were no significant differences in predictive field compensation or kinematic errors between limbs, suggesting that participants using either the left or the right arm could adapt equally well to novel dynamics. It therefore appears that the distinct preferences in control mechanisms typically observed for the dominant and nondominant arms reflect a default mode that is based on habitual functional requirements rather than an absolute limit in capacity to access the controller specialized for the opposite limb. Copyright © 2016 the American Physiological Society.

Robotic vision system for random bin picking with dual-arm robots

Directory of Open Access Journals (Sweden)

Kang Sangseung

2016-01-01

Full Text Available Random bin picking is one of the most challenging industrial robotics applications available. It constitutes a complicated interaction between the vision system, robot, and control system. For a packaging operation requiring a pick-and-place task, the robot system utilized should be able to perform certain functions for recognizing the applicable target object from randomized objects in a bin. In this paper, we introduce a robotic vision system for bin picking using industrial dual-arm robots. The proposed system recognizes the best object from randomized target candidates based on stereo vision, and estimates the position and orientation of the object. It then sends the result to the robot control system. The system was developed for use in the packaging process of cell phone accessories using dual-arm robots.

Thrust Stand for Vertically Oriented Electric Propulsion Performance Evaluation

Science.gov (United States)

Moeller, Trevor; Polzin, Kurt A.

2010-01-01

A variation of a hanging pendulum thrust stand capable of measuring the performance of an electric thruster operating in the vertical orientation is presented. The vertical orientation of the thruster dictates that the thruster must be horizontally offset from the pendulum pivot arm, necessitating the use of a counterweight system to provide a neutrally-stable system. Motion of the pendulum arm is transferred through a balance mechanism to a secondary arm on which deflection is measured. A non-contact light-based transducer is used to measure displacement of the secondary beam. The members experience very little friction, rotating on twisting torsional pivots with oscillatory motion attenuated by a passive, eddy current damper. Displacement is calibrated using an in situ thrust calibration system. Thermal management and self-leveling systems are incorporated to mitigate thermal and mechanical drifts. Gravitational restoring force and torsional spring constants associated with flexure pivots provide restoring moments. An analysis of the design indicates that the thrust measurement range spans roughly four decades, with the stand capable of measuring thrust up to 12 N for a 200 kg thruster and up to approximately 800 mN for a 10 kg thruster. Data obtained from calibration tests performed using a 26.8 lbm simulated thruster indicated a resolution of 1 mN on 100 mN-level thrusts, while those tests conducted on 200 lbm thruster yielded a resolution of roughly 2.5 micro at thrust levels of 0.5 N and greater.

Thrust stand for vertically oriented electric propulsion performance evaluation

Energy Technology Data Exchange (ETDEWEB)

Moeller, Trevor [University of Tennessee Space Institute, Tullahoma, Tennessee 37388 (United States); Polzin, Kurt A. [NASA, Marshall Space Flight Center, Huntsville, Alabama 35812 (United States)

2010-11-15

A variation of a hanging pendulum thrust stand capable of measuring the performance of an electric thruster operating in the vertical orientation is presented. The vertical orientation of the thruster dictates that the thruster must be horizontally offset from the pendulum pivot arm, necessitating the use of a counterweight system to provide a neutrally stable system. Motion of the pendulum arm is transferred through a balance mechanism to a secondary arm on which deflection is measured. A noncontact light-based transducer is used to measure displacement of the secondary beam. The members experience very little friction, rotating on twisting torsional pivots with oscillatory motion attenuated by a passive, eddy-current damper. Displacement is calibrated using an in situ thrust calibration system. Thermal management and self-leveling systems are incorporated to mitigate thermal and mechanical drifts. Gravitational force and torsional spring constants associated with flexure pivots provide restoring moments. An analysis of the design indicates that the thrust measurement range spans roughly four decades, with the stand capable of measuring thrust up to 12 N for a 200 kg thruster and up to approximately 800 mN for a 10 kg thruster. Data obtained from calibration tests performed using a 26.8 lbm simulated thruster indicated a resolution of 1 mN on 100 mN level thrusts, while those tests conducted on a 200 lbm thruster yielded a resolution of roughly 2.5 mN at thrust levels of 0.5 N and greater.

Thrust stand for vertically oriented electric propulsion performance evaluation

International Nuclear Information System (INIS)

Moeller, Trevor; Polzin, Kurt A.

2010-01-01

A variation of a hanging pendulum thrust stand capable of measuring the performance of an electric thruster operating in the vertical orientation is presented. The vertical orientation of the thruster dictates that the thruster must be horizontally offset from the pendulum pivot arm, necessitating the use of a counterweight system to provide a neutrally stable system. Motion of the pendulum arm is transferred through a balance mechanism to a secondary arm on which deflection is measured. A noncontact light-based transducer is used to measure displacement of the secondary beam. The members experience very little friction, rotating on twisting torsional pivots with oscillatory motion attenuated by a passive, eddy-current damper. Displacement is calibrated using an in situ thrust calibration system. Thermal management and self-leveling systems are incorporated to mitigate thermal and mechanical drifts. Gravitational force and torsional spring constants associated with flexure pivots provide restoring moments. An analysis of the design indicates that the thrust measurement range spans roughly four decades, with the stand capable of measuring thrust up to 12 N for a 200 kg thruster and up to approximately 800 mN for a 10 kg thruster. Data obtained from calibration tests performed using a 26.8 lbm simulated thruster indicated a resolution of 1 mN on 100 mN level thrusts, while those tests conducted on a 200 lbm thruster yielded a resolution of roughly 2.5 mN at thrust levels of 0.5 N and greater.

[Changes in titin and myosin heavy chain isoform composition in skeletal muscles of Mongolian gerbil (Meriones unguiculatus) after 12-day spaceflight].

Science.gov (United States)

Okuneva, A D; Vikhliantsev, I M; Shpagina, M D; Rogachevskiĭ, V V; Khutsian, S S; Poddubnaia, Z A; Grigor'ev, A I

2012-01-01

Changes of titin and myosin heavy chain isoform composition in skeletal muscles (m. soleus, m. gastrocnemius, m. tibialis anterior, m. psoas major) in Mongolian Gerbil (Meriones unguiculatus ) were investigated after 12-day spaceflight on board of Russian space vehicle "Foton-M3". In m. psoas and m. soleus in the gerbils from "Flight" group the expected increase in the content of fast myosin heavy chain isoforms (IIxd and IIa, respectively) were observed. No significant differences were found in the content of IIxd and IIa isoforms of myosin heavy chain in m. tibialis anterior in the gerbils from control group as compared to that in "Flight" group. An unexpected increase in the content of slow myosin heavy chain I isoform and a decrease in the content of fast IIx/d isoform in m. gastrocnemius of the gerbils from "Flight" group were observed. In skeletal muscles of the gerbils from "Flight" group the relative content of titin N2A-isoform was reduced (by 1,2-1,7 times), although the content of its NT-isoform, which was revealed in striated muscles of mammals in our experiments earlier, remained the same. When the content of titin N2A-isoform was decreased, no predictable abnormalities in sarcomeric structure and contractile ability of skeletal muscles in the gerbils from "Flight" group were found. An assumption on the leading role of titin NT-isoform in maintenance of structural and functional properties of striated muscles of mammals was made.

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

Science.gov (United States)

Zhu, Jie; Burakov, Anton; Rodionov, Vladimir

2010-01-01

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

Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

Science.gov (United States)

Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-06-07

Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

Determining the impact of oxidation on the motility of single muscle-fibres expressing different myosin isoforms

DEFF Research Database (Denmark)

Spanos, Dimitrios; Li, M.; Baron, Caroline P.

2013-01-01

heavy chain (MyHC) isoforms has not been previously investigated. Oxidation of myosin isolated from muscle fibres originating from various porcine muscles with a different metabolic profile was studied using a single muscle fibre in-vitro motility assay, allowing measurements of catalytic properties...... (motility speed) and force-generation capacity of specific MyHC isoforms. In the experimental procedure, single muscle fibres were split in different segments and each segment was exposed to a different concentration of hydrogen peroxide. Speed and force measurements were recorded and compared, to assess...... the effect of myosin oxidation on motility and force. The MyHC isoform expression in the single muscle fibre was subsequently determined on silver-stained gel SDS-PAGE. Preliminary results indicate a decrease of directionality and speed of the in-vitro motility as a result of an oxidative environment...

Characterizing and predicting submovements during human three-dimensional arm reaches.

Directory of Open Access Journals (Sweden)

James Y Liao

Full Text Available We have demonstrated that 3D target-oriented human arm reaches can be represented as linear combinations of discrete submovements, where the submovements are a set of minimum-jerk basis functions for the reaches. We have also demonstrated the ability of deterministic feed-forward Artificial Neural Networks (ANNs to predict the parameters of the submovements. ANNs were trained using kinematic data obtained experimentally from five human participants making target-directed movements that were decomposed offline into minimum-jerk submovements using an optimization algorithm. Under cross-validation, the ANNs were able to accurately predict the parameters (initiation-time, amplitude, and duration of the individual submovements. We also demonstrated that the ANNs can together form a closed-loop model of human reaching capable of predicting 3D trajectories with VAF >95.9% and RMSE ≤4.32 cm relative to the actual recorded trajectories. This closed-loop model is a step towards a practical arm trajectory generator based on submovements, and should be useful for the development of future arm prosthetic devices that are controlled by brain computer interfaces or other user interfaces.

Gripper driving device for moving a fuel up and down in a reactor

International Nuclear Information System (INIS)

Hatakenaka, Hideo.

1975-01-01

Object: To use a rope in one system to effect upward and downward movement of the gripper and opening and closing operation of a gripper opening and closing pawl to make the device smaller and the mechanism simpler. Structure: The device comprises two rope winding drums synchronously driven by a driving source for upward and downward movement of a gripper, a guide pulley arranged upwardly of each rope winding drum and displaced in relatively up and down opposite direction by a pawl operating portion for opening and closing the gripper, a gripper provided with a double-arm oscillating lever for suspending and supporting a rope and operating the opening and closing pawl supported within the gripper body and an actuator for operating the opening and closing pawl interlocked and connected to said lever, and two ropes mounted on the double arm lever of the gripper passing over the guide pulleys from the winding drums. (Kamimura, M.)

Association of Myosin Va and Schwann cells-derived RNA in mammal myelinated axons, analyzed by immunocytochemistry and confocal FRET microscopy.

Science.gov (United States)

Canclini, Lucía; Wallrabe, Horst; Di Paolo, Andrés; Kun, Alejandra; Calliari, Aldo; Sotelo-Silveira, José Roberto; Sotelo, José Roberto

2014-03-15

Evidence from multiple sources supports the hypothesis that Schwann cells in the peripheral nervous system transfer messenger RNA and ribosomes to the axons they ensheath. Several technical and methodological difficulties exist for investigators to unravel this process in myelinated axons - a complex two-cell unit. We present an experimental design to demonstrate that newly synthesized RNA is transferred from Schwann cells to axons in association with Myosin Va. The use of quantitative confocal FRET microscopy to track newly-synthesized RNA and determine the molecular association with Myosin Va, is described in detail. Copyright © 2013 Elsevier Inc. All rights reserved.

AN EMPIRICAL SURVEY ON BASIC MILITARY TRAINING IN SLOVENIAN ARMED FORCES

Directory of Open Access Journals (Sweden)

Maja GARB

2014-04-01

Full Text Available Before employment in the Slovenian Armed Forces, all candidates have to finish basic military training. The empirical survey, done in 2011 on a group of military candidates in a Slovenian Training Center, checked the motivation, level of skills and education, attitudes of leaders, military identity, prestige and social support of these candidates. The results confirmed the skills’ and fighters’ orientation of Slovenian soldiers, but surprised with the paleomodern motivators for military job.

/sup 99m/Tc labeling of antibodies to cardiac myosin Fab and to human fibrinogen

International Nuclear Information System (INIS)

Khaw, B.A.; Strauss, H.W.; Carvalho, A.; Locke, E.; Gold, H.K.; Haber, E.

1982-01-01

We have developed a method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with /sup 99m/Tc at neutral pH. This method uses dithionite reduction of pertechnetate and subsequent labeling, to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the /sup 99m/Tc D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80--88% coagulable. The /sup 99m/Tc AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the /sup 99m/Tc labeling of other biologically active and acid-labile macromolecules

A Novel Alpha Cardiac Actin (ACTC1 Mutation Mapping to a Domain in Close Contact with Myosin Heavy Chain Leads to a Variety of Congenital Heart Defects, Arrhythmia and Possibly Midline Defects.

Directory of Open Access Journals (Sweden)

Céline Augière

Full Text Available A Lebanese Maronite family presented with 13 relatives affected by various congenital heart defects (mainly atrial septal defects, conduction tissue anomalies and midline defects. No mutations were found in GATA4 and NKX2-5.A set of 399 poly(AC markers was used to perform a linkage analysis which peaked at a 2.98 lod score on the long arm of chromosome 15. The haplotype analysis delineated a 7.7 meganucleotides genomic interval which included the alpha-cardiac actin gene (ACTC1 among 36 other protein coding genes. A heterozygous missense mutation was found (c.251T>C, p.(Met84Thr in the ACTC1 gene which changed a methionine residue conserved up to yeast. This mutation was absent from 1000 genomes and exome variant server database but segregated perfectly in this family with the affection status. This mutation and 2 other ACTC1 mutations (p.(Glu101Lys and p.(Met125Val which result also in congenital heart defects are located in a region in close apposition to a myosin heavy chain head region by contrast to 3 other alpha-cardiac actin mutations (p.(Ala297Ser,p.(Asp313His and p.(Arg314His which result in diverse cardiomyopathies and are located in a totally different interaction surface.Alpha-cardiac actin mutations lead to congenital heart defects, cardiomyopathies and eventually midline defects. The consequence of an ACTC1 mutation may in part be dependent on the interaction surface between actin and myosin.

ARM Cloud Radar Simulator Package for Global Climate Models Value-Added Product

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yuying [North Carolina State Univ., Raleigh, NC (United States); Xie, Shaocheng [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-05-01

wherever possible. The ARM simulator is written in Fortran 90, just as is the COSP. It is incorporated into COSP to facilitate use by the climate modeling community. In order to evaluate simulator output, the observational counterpart of the simulator output, radar reflectivity-height histograms (CFAD) is also generated from the ARM observations. This report includes an overview of the ARM cloud radar simulator VAP and the required simulator-oriented ARM radar data product (radarCFAD) for validating simulator output, as well as a user guide for operating the ARM radar simulator VAP.

Stirling engine power control and motion conversion mechanism

Science.gov (United States)

Marks, David T.

1983-01-01

A motion conversion device for converting between the reciprocating motion of the pistons in a Stirling engine and the rotating motion of its output shaft, and for changing the stroke and phase of the pistons, includes a lever pivoted at one end and having a cam follower at the other end. The piston rod engages the lever intermediate its ends and the cam follower engages a cam keyed to the output shaft. The lever pivot can be moved to change the length of the moment arm defined between the cam follower and the piston rod the change the piston stroke and force exerted on the cam, and the levers can be moved in opposite directions to change the phase between pistons.

Isolated effects of peripheral arm and central body cooling on arm performance.

Science.gov (United States)

Giesbrecht, G G; Wu, M P; White, M D; Johnston, C E; Bristow, G K

1995-10-01

Whole body cooling impairs manual arm performance. The independent contributions of local (peripheral) and/or whole body (central) cooling are not known. Therefore, a protocol was developed in which the arm and the rest of the body could be independently cooled. Biceps temperature (Tmus), at a depth of 20 mm, and esophageal temperature (Tes) were measured. Six subjects were immersed to the clavicles in a tank (body tank) of water under 3 conditions: 1) cold body-cold arm (CB-CA); 2) warm body-cold arm (WB-CA); and 3) cold body-warm arm (CB-WA). In the latter two conditions, subjects placed their dominant arm in a separate (arm) tank. Water temperature (Tw) in each tank was independently controlled. In conditions requiring cold body and/or cold arm, Tw in the appropriate tanks was 8 degrees C. In conditions requiring warm body and/or warm arm, Tw in the appropriate tanks was adjusted between 29 and 38 degrees C to maintain body/arm temperature at baseline values. A battery of 6 tests, requiring fine or gross motor movements, were performed immediately before immersion and after 15, 45, and 70 minutes of immersion. In CB-CA, Tes decreased from an average of 37.2 to 35.6 degrees C and Tmus decreased from 34.6 to 22.0 degrees C. In WB-CA, Tmus decreased to 18.1 degrees C (Tes = 37.1 degrees C), and in CB-WA, Tes decreased to 35.8 degrees C (Tmus = 34.5 degrees C). By the end of immersion, there were significant decrements (43-85%) in the performance of all tests in CB-CA and WB-CA (p body and/or the arm elicits large decrements in finger, hand and arm performance. The decrements are due almost entirely to the local effects of arm tissue cooling.

Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

Science.gov (United States)

Weil, D; Levy, G; Sahly, I; Levi-Acobas, F; Blanchard, S; El-Amraoui, A; Crozet, F; Philippe, H; Abitbol, M; Petit, C

1996-04-16

The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.

Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use

Science.gov (United States)

Young, Erica J.; Blouin, Ashley M.; Briggs, Sherri B.; Sillivan, Stephanie E.; Lin, Li; Cameron, Michael D.; Rumbaugh, Gavin; Miller, Courtney A.

2015-01-01

Memories associated with drug use increase vulnerability to relapse in substance use disorder (SUD) and there are no pharmacotherapies for the prevention of relapse. Previously, we reported a promising finding that storage of memories associated with methamphetamine (METH), but not memories for fear or food reward, is vulnerable to disruption by actin depolymerization in the basolateral amygdala complex (BLC). However, actin is not a viable therapeutic target because of its numerous functions throughout the body. Here we report the discovery of a viable therapeutic target, nonmuscle myosin II (NMIIB), a molecular motor that supports memory by directly driving synaptic actin polymerization. A single intra-BLC treatment with Blebbistatin, a small molecule inhibitor of class II myosin isoforms, including NMIIB, produced a long-lasting disruption of context-induced drug seeking (at least 30 days). Further, post-consolidation genetic knockdown of Myh10, the heavy chain of the most highly expressed NMII in the BLC, was sufficient to produce METH-associated memory loss. Blebbistatin was found to be highly brain penetrant. A single systemic injection of the compound selectively disrupted the storage of METH-associated memory and reversed the accompanying increase in BLC spine density. This effect was specific to METH-associated memory, as it had no effect on an auditory fear memory. The effect was also independent of retrieval, as METH-associated memory was disrupted twenty-four hours after a single systemic injection of Blebbistatin delivered in the home cage. Together, these results argue for the further development of small molecule inhibitors of nonmuscle myosin II as potential therapeutics for the prevention of SUD relapse triggered by drug associations. PMID:26239291

Have Third-World Arms Industries Reduced Arms Imports?

OpenAIRE

Looney, R.E.

1989-01-01

Current Research on Peace and Violence, no. 1, 1989. Refereed Journal Article In 1945 only Argentina, Brazil, India and South Africa in the Third World possessed domestic arms industries which produced weapons systems other than small arms and ammunition (SIPRI, 1987, 76).

Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

Directory of Open Access Journals (Sweden)

James N. Cobley

2016-04-01

Full Text Available Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM. We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.

Arm Pain

Science.gov (United States)

... be a sign of a heart attack. Seek emergency treatment if you have: Arm, shoulder or back ... http://www.mayoclinic.org/symptoms/arm-pain/basics/definition/SYM-20050870 . Mayo Clinic Footer Legal Conditions and ...

Cell differentiation through tissue elasticity-coupled, myosin-driven remodeling.

Science.gov (United States)

Zajac, Allison L; Discher, Dennis E

2008-12-01

Cells may lack eyes to see and ears to hear, but cells do seem to have a sense of 'touch' that allows them to feel their microenvironment. This is achieved in part through contractility coupled adhesion to physically flexible 'soft' tissue. Here we summarize some of the known variations in elasticity of solid tissue and review some of the long-term effects of cells 'feeling' this elasticity, focusing on differentiation processes of both committed cell types and stem cells. We then highlight what is known of molecular remodeling in cells under stress on short time scales. Key roles for forces generated by ubiquitous and essential myosin-II motors in feedback remodeling are emphasized throughout.

Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells.

Science.gov (United States)

Kampourakis, Thomas; Yan, Ziqian; Gautel, Mathias; Sun, Yin-Biao; Irving, Malcolm

2014-12-30

Myosin binding protein-C (MyBP-C) is a key regulatory protein in heart muscle, and mutations in the MYBPC3 gene are frequently associated with cardiomyopathy. However, the mechanism of action of MyBP-C remains poorly understood, and both activating and inhibitory effects of MyBP-C on contractility have been reported. To clarify the function of the regulatory N-terminal domains of MyBP-C, we determined their effects on the structure of thick (myosin-containing) and thin (actin-containing) filaments in intact sarcomeres of heart muscle. We used fluorescent probes on troponin C in the thin filaments and on myosin regulatory light chain in the thick filaments to monitor structural changes associated with activation of demembranated trabeculae from rat ventricle by the C1mC2 region of rat MyBP-C. C1mC2 induced larger structural changes in thin filaments than calcium activation, and these were still present when active force was blocked with blebbistatin, showing that C1mC2 directly activates the thin filaments. In contrast, structural changes in thick filaments induced by C1mC2 were smaller than those associated with calcium activation and were abolished or reversed by blebbistatin. Low concentrations of C1mC2 did not affect resting force but increased calcium sensitivity and reduced cooperativity of force and structural changes in both thin and thick filaments. These results show that the N-terminal region of MyBP-C stabilizes the ON state of thin filaments and the OFF state of thick filaments and lead to a novel hypothesis for the physiological role of MyBP-C in the regulation of cardiac contractility.

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

Energy Technology Data Exchange (ETDEWEB)

Wasik, Anita A.; Dumont, Vincent [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Tienari, Jukka [Department of Pathology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, 05850 Hyvinkää (Finland); Nyman, Tuula A. [Institute of Biotechnology, University of Helsinki, 00014 Helsinki (Finland); Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Lehtonen, Eero [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Laboratory Animal Centre, University of Helsinki, 00014 Helsinki (Finland); Groop, Per-Henrik [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Baker IDI Heart & Diabetes Institute, 3004 Melbourne (Australia); Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland)

2017-01-15

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

International Nuclear Information System (INIS)

Wasik, Anita A.; Dumont, Vincent; Tienari, Jukka; Nyman, Tuula A.; Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku; Lehtonen, Eero; Groop, Per-Henrik; Lehtonen, Sanna

2017-01-01

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

Harmonic Force Spectroscopy Reveals a Force-Velocity Curve from a Single Human Beta Cardiac Myosin Motor

DEFF Research Database (Denmark)

Sung, Jongmin; Nag, Suman; Vestergaard, Christian L.

2014-01-01

human beta cardiac myosin S1. We also compare load-velocity curves for wild-type motors with load-velocity curves of mutant forms that cause hypertrophic or dilated-cardiomyopathy (HCM or DCM), in order to understand the effects of mutations on the contractile cycle at the single molecule level....

Electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength after stroke.

Science.gov (United States)

Mehrholz, Jan; Pohl, Marcus; Platz, Thomas; Kugler, Joachim; Elsner, Bernhard

2015-11-07

Electromechanical and robot-assisted arm training devices are used in rehabilitation, and may help to improve arm function after stroke. To assess the effectiveness of electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength in people after stroke. We also assessed the acceptability and safety of the therapy. We searched the Cochrane Stroke Group's Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 3), MEDLINE (1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), SPORTDiscus (1949 to March 2015), PEDro (searched April 2015), Compendex (1972 to March 2015), and Inspec (1969 to March 2015). We also handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trialists, experts, and researchers in our field, as well as manufacturers of commercial devices. Randomised controlled trials comparing electromechanical and robot-assisted arm training for recovery of arm function with other rehabilitation or placebo interventions, or no treatment, for people after stroke. Two review authors independently selected trials for inclusion, assessed trial quality and risk of bias, and extracted data. We contacted trialists for additional information. We analysed the results as standardised mean differences (SMDs) for continuous variables and risk differences (RDs) for dichotomous variables. We included 34 trials (involving 1160 participants) in this update of our review. Electromechanical and robot-assisted arm training improved activities of daily living scores (SMD 0.37, 95% confidence interval (CI) 0.11 to 0.64, P = 0.005, I² = 62%), arm function (SMD 0.35, 95% CI 0.18 to 0.51, P arm muscle strength (SMD 0.36, 95% CI 0.01 to 0.70, P = 0.04, I² = 72%), but the quality of the evidence was low to very low

Fostering development of nursing practices to support integrated care when implementing integrated care pathways: what levers to use?

Science.gov (United States)

Longpré, Caroline; Dubois, Carl-Ardy

2017-11-29

Care integration has been the focus of recent health system reforms. Given their functions at all levels of the care continuum, nurses have a substantial and primordial role to play in such integration processes. The aim of this study was to identify levers and strategies that organizations can use to support the development of a nursing practice aligned with the requirements of care integration in a health and social services centre (HSSC) in Quebec. The research design was a cross-sectional descriptive qualitative study based on a single case study with nested levels of analysis. The case was a public, multi-disciplinary HSSC in a semi-urban region of Quebec. Semi-structured interviews with 37 persons (nurses, professionals, managers, administrators) allowed for data saturation and ensured theoretical representation by covering four care pathways constituting different care integration contexts. Analysis involved four steps: preparing a predetermined list of codes based on the reference framework developed by Minkman (2011); coding transcript content; developing general and summary matrices to group observations for each care pathway; and creating a general model showing the overall results for the four pathways. The organization's capacity for response with regard to developing an integrated system of services resulted in two types of complementary interventions. The first involved investing in key resources and renewing organizational structures; the second involved deploying a series of organizational and clinical-administrative processes. In resource terms, integration efforts resulted in setting up new strategic services, re-arranging physical infrastructures, and deploying new technological resources. Organizational and clinical-administrative processes to promote integration involved renewing governance, improving the flow of care pathways, fostering continuous quality improvement, developing new roles, promoting clinician collaboration, and strengthening

Upper ankle joint space detection on low contrast intraoperative fluoroscopic C-arm projections

Science.gov (United States)

Thomas, Sarina; Schnetzke, Marc; Brehler, Michael; Swartman, Benedict; Vetter, Sven; Franke, Jochen; Grützner, Paul A.; Meinzer, Hans-Peter; Nolden, Marco

2017-03-01

Intraoperative mobile C-arm fluoroscopy is widely used for interventional verification in trauma surgery, high flexibility combined with low cost being the main advantages of the method. However, the lack of global device-to- patient orientation is challenging, when comparing the acquired data to other intrapatient datasets. In upper ankle joint fracture reduction accompanied with an unstable syndesmosis, a comparison to the unfractured contralateral site is helpful for verification of the reduction result. To reduce dose and operation time, our approach aims at the comparison of single projections of the unfractured ankle with volumetric images of the reduced fracture. For precise assessment, a pre-alignment of both datasets is a crucial step. We propose a contour extraction pipeline to estimate the joint space location for a prealignment of fluoroscopic C-arm projections containing the upper ankle joint. A quadtree-based hierarchical variance comparison extracts potential feature points and a Hough transform is applied to identify bone shaft lines together with the tibiotalar joint space. By using this information we can define the coarse orientation of the projections independent from the ankle pose during acquisition in order to align those images to the volume of the fractured ankle. The proposed method was evaluated on thirteen cadaveric datasets consisting of 100 projections each with manually adjusted image planes by three trauma surgeons. The results show that the method can be used to detect the joint space orientation. The correlation between angle deviation and anatomical projection direction gives valuable input on the acquisition direction for future clinical experiments.

A Collapsin Response Mediator Protein 2 Isoform Controls Myosin II-Mediated Cell Migration and Matrix Assembly by Trapping ROCK II

Science.gov (United States)

Morgan-Fisher, Marie; Wait, Robin; Couchman, John R.; Wewer, Ulla M.

2012-01-01

Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions through the inhibition of ROCK II in nonneuronal cells. PMID:22431514

Mathematical modeling of Myosin induced bistability of Lamellipodial fragments.

Science.gov (United States)

Hirsch, S; Manhart, A; Schmeiser, C

2017-01-01

For various cell types and for lamellipodial fragments on flat surfaces, externally induced and spontaneous transitions between symmetric nonmoving states and polarized migration have been observed. This behavior is indicative of bistability of the cytoskeleton dynamics. In this work, the Filament Based Lamellipodium Model (FBLM), a two-dimensional, anisotropic, two-phase continuum model for the dynamics of the actin filament network in lamellipodia, is extended by a new description of actin-myosin interaction. For appropriately chosen parameter values, the resulting model has bistable dynamics with stable states showing the qualitative features observed in experiments. This is demonstrated by numerical simulations and by an analysis of a strongly simplified version of the FBLM with rigid filaments and planar lamellipodia at the cell front and rear.

The radiographic acromiohumeral interval is affected by arm and radiographic beam position

Energy Technology Data Exchange (ETDEWEB)

Fehringer, Edward V.; Rosipal, Charles E.; Rhodes, David A.; Lauder, Anthony J.; Feschuk, Connie A.; Mormino, Matthew A.; Hartigan, David E. [University of Nebraska Medical Center, Department of Orthopaedic Surgery and Rehabilitation, Omaha, NE (United States); Puumala, Susan E. [Nebraska Medical Center, Department of Preventive and Societal Medicine, Omaha, NE (United States)

2008-06-15

The objective was to determine whether arm and radiographic beam positional changes affect the acromiohumeral interval (AHI) in radiographs of healthy shoulders. Controlling for participant's height and position as well as radiographic beam height and angle, from 30 right shoulders of right-handed males without shoulder problems four antero-posterior (AP) radiographic views each were obtained in defined positions. Three independent, blinded physicians measured the AHI to the nearest millimeter in 120 randomized radiographs. Mean differences between measurements were calculated, along with a 95% confidence interval. Controlling for observer effect, there was a significant difference between AHI measurements on different views (p<0.01). All pair-wise differences were statistically significant after adjusting for multiple comparisons (all p values <0.01). Even in healthy shoulders, small changes in arm position and radiographic beam orientation affect the AHI in radiographs. (orig.)

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function.

Science.gov (United States)

Alamo, Lorenzo; Koubassova, Natalia; Pinto, Antonio; Gillilan, Richard; Tsaturyan, Andrey; Padrón, Raúl

2017-10-01

The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0 nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5 nm, achieved by cryo-EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, "free" and "blocked", formed an asymmetric structure named the "interacting-heads motif" (IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca 2+ -activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and post-tetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.

ARM Airborne Carbon Measurements (ARM-ACME) and ARM-ACME 2.5 Final Campaign Reports

Energy Technology Data Exchange (ETDEWEB)

Biraud, S. C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Tom, M. S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sweeney, C. [NOAA Earth Systems Research Lab., Boulder, CO (United States)

2016-01-01

We report on a 5-year multi-institution and multi-agency airborne study of atmospheric composition and carbon cycling at the Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Southern Great Plains (SGP) site, with scientific objectives that are central to the carbon-cycle and radiative-forcing goals of the U.S. Global Change Research Program and the North American Carbon Program (NACP). The goal of these measurements is to improve understanding of 1) the carbon exchange of the Atmospheric Radiation Measurement (ARM) SGP region; 2) how CO₂ and associated water and energy fluxes influence radiative-forcing, convective processes, and CO₂ concentrations over the ARM SGP region, and 3) how greenhouse gases are transported on continental scales.

Powered manipulator control arm

International Nuclear Information System (INIS)

Le Mouee, Theodore; Vertut, Jean; Marchal, Paul; Germon, J.C.; Petit, Michel

1975-01-01

A remote operated control arm for powered manipulators is described. It includes an assembly allowing several movements with position sensors for each movement. The number of possible arm movements equals the number of possible manipulator movements. The control systems may be interrupted as required. One part of the arm is fitted with a system to lock it with respect to another part of the arm without affecting the other movements, so long as the positions of the manipulator and the arm have not been brought into complete coincidence. With this system the locking can be ended when complete concordance is achieved [fr

ARM Airborne Carbon Measurements VI (ARM-ACME VI) Field Campaign Report

Energy Technology Data Exchange (ETDEWEB)

Biraud, Sebastien [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2017-05-01

From October 1, 2015 through September 30, 2016, AAF deployed a Cessna 206 aircraft over the Southern Great Plains, collecting observations of trace gas mixing ratios over the ARM/SGP Central Facility. The aircraft payload included two Atmospheric Observing Systems (AOS Inc.) analyzers for continuous measurements of CO2, and a 12-flask sampler for analysis of carbon cycle gases (CO2, CO, CH4, N2O, 13CO2). The aircraft payload also includes solar/infrared radiation measurements. This research (supported by DOE ARM and TES programs) builds upon previous ARM-ACME missions. The goal of these measurements is to improve understanding of: (a) the carbon exchange of the ARM region; (b) how CO2 and associated water and energy fluxes influence radiative forcing, convective processes, and CO2 concentrations over the ARM region, and (c) how greenhouse gases are transported on continental scales.

Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging: implications for functional defects in aged eggs

Science.gov (United States)

Mackenzie, Amelia C.L.; Kyle, Diane D.; McGinnis, Lauren A.; Lee, Hyo J.; Aldana, Nathalia; Robinson, Douglas N.; Evans, Janice P.

2016-01-01

STUDY HYPOTHESIS Cellular aging of the egg following ovulation, also known as post-ovulatory aging, is associated with aberrant cortical mechanics and actomyosin cytoskeleton functions. STUDY FINDING Post-ovulatory aging is associated with dysfunction of non-muscle myosin-II, and pharmacologically induced myosin-II dysfunction produces some of the same deficiencies observed in aged eggs. WHAT IS KNOWN ALREADY Reproductive success is reduced with delayed fertilization and when copulation or insemination occurs at increased times after ovulation. Post-ovulatory aged eggs have several abnormalities in the plasma membrane and cortex, including reduced egg membrane receptivity to sperm, aberrant sperm-induced cortical remodeling and formation of fertilization cones at the site of sperm entry, and reduced ability to establish a membrane block to prevent polyspermic fertilization. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Ovulated mouse eggs were collected at 21–22 h post-human chorionic gonadotrophin (hCG) (aged eggs) or at 13–14 h post-hCG (young eggs), or young eggs were treated with the myosin light chain kinase (MLCK) inhibitor ML-7, to test the hypothesis that disruption of myosin-II function could mimic some of the effects of post-ovulatory aging. Eggs were subjected to various analyses. Cytoskeletal proteins in eggs and parthenogenesis were assessed using fluorescence microscopy, with further analysis of cytoskeletal proteins in immunoblotting experiments. Cortical tension was measured through micropipette aspiration assays. Egg membrane receptivity to sperm was assessed in in vitro fertilization (IVF) assays. Membrane topography was examined by low-vacuum scanning electron microscopy (SEM). MAIN RESULTS AND THE ROLE OF CHANCE Aged eggs have decreased levels and abnormal localizations of phosphorylated myosin-II regulatory light chain (pMRLC; P = 0.0062). Cortical tension, which is mediated in part by myosin-II, is reduced in aged mouse eggs when compared with

Radioimmunoassay of myosin heavy beta chains in human serum for the evaluation of the size of myocardial infarction: correlation with myocardial Tl-201 SPECT and cardiac angioscintigraphy

International Nuclear Information System (INIS)

Facello, A.; Gries, P.; Demangeat, C.; Brunot, B.; Roul, G.; Demangeat, J.L.; Moulichon, M.; Bareiss, P.; Sacrez, A.; Constantinesco, A.

1990-01-01

To determine the relationship between serum levels of myosin heavy beta chains assessed by an IRMA technique and other radionuclide and enzymatic parameters in the evaluation of the size of myocardial infarction, we studied 22 patients with acute myocardial infarction. Blood samples taken daily between 1st to 13th day of evolution allow the determination of peak and integral of myosine release that showed a good correlation (p [fr

C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation.

Science.gov (United States)

Harris, Samantha P; Belknap, Betty; Van Sciver, Robert E; White, Howard D; Galkin, Vitold E

2016-02-09

Mutations in genes encoding myosin, the molecular motor that powers cardiac muscle contraction, and its accessory protein, cardiac myosin binding protein C (cMyBP-C), are the two most common causes of hypertrophic cardiomyopathy (HCM). Recent studies established that the N-terminal domains (NTDs) of cMyBP-C (e.g., C0, C1, M, and C2) can bind to and activate or inhibit the thin filament (TF). However, the molecular mechanism(s) by which NTDs modulate interaction of myosin with the TF remains unknown and the contribution of each individual NTD to TF activation/inhibition is unclear. Here we used an integrated structure-function approach using cryoelectron microscopy, biochemical kinetics, and force measurements to reveal how the first two Ig-like domains of cMyPB-C (C0 and C1) interact with the TF. Results demonstrate that despite being structural homologs, C0 and C1 exhibit different patterns of binding on the surface of F-actin. Importantly, C1 but not C0 binds in a position to activate the TF by shifting tropomyosin (Tm) to the "open" structural state. We further show that C1 directly interacts with Tm and traps Tm in the open position on the surface of F-actin. Both C0 and C1 compete with myosin subfragment 1 for binding to F-actin and effectively inhibit actomyosin interactions when present at high ratios of NTDs to F-actin. Finally, we show that in contracting sarcomeres, the activating effect of C1 is apparent only once low levels of Ca(2+) have been achieved. We suggest that Ca(2+) modulates the interaction of cMyBP-C with the TF in the sarcomere.

ARM Mentor Selection Process

Energy Technology Data Exchange (ETDEWEB)

Sisterson, D. L. [Argonne National Lab. (ANL), Argonne, IL (United States)

2015-10-01

The Atmospheric Radiation Measurement (ARM) Program was created in 1989 with funding from the U.S. Department of Energy (DOE) to develop several highly instrumented ground stations to study cloud formation processes and their influence on radiative transfer. In 2003, the ARM Program became a national scientific user facility, known as the ARM Climate Research Facility. This scientific infrastructure provides for fixed sites, mobile facilities, an aerial facility, and a data archive available for use by scientists worldwide through the ARM Climate Research Facility—a scientific user facility. The ARM Climate Research Facility currently operates more than 300 instrument systems that provide ground-based observations of the atmospheric column. To keep ARM at the forefront of climate observations, the ARM infrastructure depends heavily on instrument scientists and engineers, also known as lead mentors. Lead mentors must have an excellent understanding of in situ and remote-sensing instrumentation theory and operation and have comprehensive knowledge of critical scale-dependent atmospheric processes. They must also possess the technical and analytical skills to develop new data retrievals that provide innovative approaches for creating research-quality data sets. The ARM Climate Research Facility is seeking the best overall qualified candidate who can fulfill lead mentor requirements in a timely manner.

The arms race control

International Nuclear Information System (INIS)

Nemo, J.

2010-01-01

Written in 1961, this paper presents the content of a book entitled 'The arms race control' where the author outlined the difference between disarmament and arms control, described the economic and moral role of arms race, the importance of force balance for international security. He wandered whether arms control could ensure this balance and whether nuclear balance meant force balance. Force balance then appears to be a precarious and unsteady component of international security. He commented the challenges of disarmament, recalled some arguments for a nuclear disarmament. Then he discussed what would be an arms control with or without disarmament (either nuclear or conventional)

How do octopuses use their arms?

Science.gov (United States)

Mather, J A

1998-09-01

A taxonomy of the movement patterns of the 8 flexible arms of octopuses is constructed. Components consist of movements of the arm itself, the ventral suckers and their stalks, as well as the relative position of arms and the skin web between them. Within 1 arm, combinations of components result in a variety of behaviors. At the level of all arms, 1 group of behaviors is described as postures, on the basis of the spread of all arms and the web to make a 2-dimensional surface whose position differs in the 3rd dimension. Another group of arm behaviors is actions, more or less coordinated and involving several to all arms. Arm control appears to be based on radial symmetry, relative equipotentiality of all arms, relative independence of each arm, and separability of components within the arm. The types and coordination of arm behaviors are discussed with relationship to biomechanical limits, muscle structures, and neuronal programming.

Health as a lever for another development.

Science.gov (United States)

Banerji, D

1978-01-01

In India the health services are unable to meet the real needs of the poor. The colonial policy of exploitation, expropriation and plunder created widespread disruption in the way of life of the Indian people. The colonialism destroyed the health culture of India and created a Western bias in the health services which continues to this day. The bias has extend to research - for example, by postulating a correlation between malnutrition and mental retardation. The commitment of the current political leadership to bypass the medical establishment and go directly to the people has created a favorable setting to challenge the basic scientific, sociological and economic premises of the earlier approach to development of the health services in India, and to formulate a new approach to development of the health services in India, and to formulate a new approach to take its place. The main premise of Another Development in the health services is to begin with the people - a framework is designed for a health service system particularly tailored to meet the needs of the people. Efforts to relieve the suffering caused by health problems can contribute to the initiation of political, economic and social action. In this context, the formulation and implementation of Another Development in Health acquires much significance: 1) the very alleviation of suffering has political significance, because it narrows the gap between the ruling classes and the masses; 2) Another Development in Health would provide an entry point for change agents, who could use the opportunity to work with the people to initiate changes in other social and economic fields; and 3) by generating social awareness, Another Development in Health may work as a lever for promoting similar developments in other social and economic fields.

Arm rehabilitation in post stroke subjects: A randomized controlled trial on the efficacy of myoelectrically driven FES applied in a task-oriented approach.

Science.gov (United States)

Jonsdottir, Johanna; Thorsen, Rune; Aprile, Irene; Galeri, Silvia; Spannocchi, Giovanna; Beghi, Ettore; Bianchi, Elisa; Montesano, Angelo; Ferrarin, Maurizio

2017-01-01

Motor recovery of persons after stroke may be enhanced by a novel approach where residual muscle activity is facilitated by patient-controlled electrical muscle activation. Myoelectric activity from hemiparetic muscles is then used for continuous control of functional electrical stimulation (MeCFES) of same or synergic muscles to promote restoration of movements during task-oriented therapy (TOT). Use of MeCFES during TOT may help to obtain a larger functional and neurological recovery than otherwise possible. Multicenter randomized controlled trial. Eighty two acute and chronic stroke victims were recruited through the collaborating facilities and after signing an informed consent were randomized to receive either the experimental (MeCFES assisted TOT (M-TOT) or conventional rehabilitation care including TOT (C-TOT). Both groups received 45 minutes of rehabilitation over 25 sessions. Outcomes were Action Research Arm Test (ARAT), Upper Extremity Fugl-Meyer Assessment (FMA-UE) scores and Disability of the Arm Shoulder and Hand questionnaire. Sixty eight subjects completed the protocol (Mean age 66.2, range 36.5-88.7, onset months 12.7, range 0.8-19.1) of which 45 were seen at follow up 5 weeks later. There were significant improvements in both groups on ARAT (median improvement: MeCFES TOT group 3.0; C-TOT group 2.0) and FMA-UE (median improvement: M-TOT 4.5; C-TOT 3.5). Considering subacute subjects (time since stroke rehabilitation (57.9%) than in the C-TOT group (33.2%) (difference in proportion improved 24.7%; 95% CI -4.0; 48.6), though the study did not meet the planned sample size. This is the first large multicentre RCT to compare MeCFES assisted TOT with conventional care TOT for the upper extremity. No adverse events or negative outcomes were encountered, thus we conclude that MeCFES can be a safe adjunct to rehabilitation that could promote recovery of upper limb function in persons after stroke, particularly when applied in the subacute phase.

An adhesome comprising laminin, dystroglycan and myosin IIA is required during notochord development in Xenopus laevis.

Science.gov (United States)

Buisson, Nicolas; Sirour, Cathy; Moreau, Nicole; Denker, Elsa; Le Bouffant, Ronan; Goullancourt, Aline; Darribère, Thierry; Bello, Valérie

2014-12-01

Dystroglycan (Dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. The function of Dg was examined in Xenopus laevis embryos by knockdown of Dg and overexpression and replacement of the endogenous Dg with a mutated form of the protein. This analysis revealed that Dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuoles. Using mutations in the cytoplasmic domain, we identified two sites that are involved in cell polarization and are required for mediolateral cell intercalation, and a site that is required for vacuolation. Furthermore, using a proteomic analysis, the cytoskeletal non-muscle myosin IIA has been identified for the first time as a molecular link between the Dg-cytoplasmic domain and cortical actin. The data allowed us to identify the adhesome laminin-Dg-myosin IIA as being required to maintain the cortical actin cytoskeleton network during vacuolation, which is crucial to maintain the shape of notochordal cells. © 2014. Published by The Company of Biologists Ltd.

CyARM: Haptic Sensing Device for Spatial Localization on Basis of Exploration by Arms

Directory of Open Access Journals (Sweden)

Junichi Akita

2009-01-01

Full Text Available We introduce a new type of perception aid device based on user's exploration action, which is named as CyARM (acronym of “Cyber Arm”. The user holds this device in her/his arm, the extension of the arm is controlled by tension in wires, which are attached to her/his body according to the distance to the object. This user interface has unique characteristics that give users the illusion of an imaginary arm that extends to existing objects. The implementations of CyARM and our two experiments to investigate the efficiency and effectiveness of CyARM are described. The results show that we could confirm that CyARM can be used to recognize the presence of an object in front of the user and to measure the relative distance to the object.

The effects of response cost and species-typical behaviors on a daily time-place learning task.

Science.gov (United States)

Deibel, Scott H; Thorpe, Christina M

2013-03-01

Two theories that have been hypothesized to mediate acquisition in daily time-place learning (TPL) tasks were investigated in a free operant daily TPL task: the response cost hypothesis and the species-typical behavior hypothesis. One lever at the end of one of the choice arms of a T-maze provided food in the morning, and 6 h later, a lever in the other choice arm provided food. Four groups were used to assess the effect of two possible sources of response cost: physical effort of the task and costs associated with foraging ecology. One group was used to assess the effect of explicitly allowing for species-typical behaviors. If only first arm choice data were considered, there was little evidence of learning. However, both first press and percentage of presses on the correct lever prior to the first reinforcement revealed evidence of TPL in most rats tested. Unexpectedly, the high response cost groups for both of the proposed sources did not perform better than the low response cost groups. The groups that allowed animals to display species-typical behaviors performed the worst. Skip session probe trials confirmed that the majority of the rats that acquired the task were using a circadian timing strategy. The results from the present study suggest that learning in free operant daily TPL tasks might not be dependent on response cost.

Cloning of skeletal myosin heavy chain gene family from adult pleopod muscle and whole larvae of shrimps.

Science.gov (United States)

Koyama, Hiroki; Piyapattanakorn, Sanit; Watabe, Shugo

2013-06-01

The physiological and biological properties of skeletal muscle in crustacea have not been well understood compared with those of vertebrates. The present study focused on myosin, the major protein in skeletal muscle, from shrimps. In our previous study, two full-length genes encoding myosin heavy chain (MHC), a large subunit of the myosin molecule, were cloned from abdominal fast skeletal muscle of kuruma Marsupenaeus japonicus, black tiger Penaeus monodon and Pacific white Penaeus vannamei shrimps, and named as MHCa and MHCb. In this study, we renamed these as MHC1 and MHC2, respectively, due to the presence of various isoforms newly identified. Partial MHC sequences were identified from pleopod muscle of these shrimps. Two MHCs, named MHC3 and MHC4, were identified from pleopod muscle of kuruma shrimp, whereas two MHCs, named MHC4 and MHC5, were cloned from Pacific white shrimp pleopod. MHC3 was cloned only from black tiger shrimp pleopod. Partial MHC sequences from zoea, mysis, and postlarvae of black tiger and Pacific white shrimps were also determined. The phylogenetic tree demonstrated that most MHCs from pleopod muscle and larval MHCs formed clades with MHC1 and MHC2, respectively. These MHCs were considered to be of fast type, since MHC1 and MHC2 are fast-type MHCs according to our previous study. MHC5 obtained from pleopod muscle of Pacific white shrimp in this study was monophyletic with American lobster Homarus americanus S2 slow tonic MHC previously reported, indicating that MHC5 from Pacific white shrimp is of slow type. Copyright © 2013 Wiley Periodicals, Inc.

PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

Directory of Open Access Journals (Sweden)

Ana E. González Wusener

2016-01-01

Full Text Available Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO cells and PTP1B reconstituted (WT cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.

PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

Science.gov (United States)

González Wusener, Ana E.; González, Ángela; Nakamura, Fumihiko; Arregui, Carlos O.

2016-01-01

ABSTRACT Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration. PMID:26700725

Myosin dephosphorylation during rapid relaxation of hog carotid artery smooth muscle.

Science.gov (United States)

Driska, S P; Stein, P G; Porter, R

1989-02-01

Changes in myosin light chain phosphorylation were measured during histamine-induced rhythmic contractions of hog carotid artery smooth muscle strips. Histamine made the muscle strips contract spontaneously every 1-5 min, and this allowed measurement of the time course of phosphorylation in relation to force development under conditions where diffusion of the agonist through tissue would not complicate the interpretation of the data. In the absence of histamine, phosphorylation was low [0.12 +/- 0.04 mol P/mol of the 20,000-Da light chain (LC 20)]. Phosphorylation was slightly (but not significantly) higher in the presence of 10 microM histamine in the relaxed state between contractions (0.20 +/- 0.03 mol P/mol LC 20). In muscle strips frozen during force development, when force had reached half of its peak value, phosphorylation was 0.38 +/- 0.06 mol P/mol LC 20. The highest levels of phosphorylation (0.49 +/- 0.04 mol P/mol LC 20) were found in strips frozen at the peak of the rhythmic contractions. Strips frozen when force had declined to half of the peak force showed low levels of phosphorylation (0.17 +/- 0.07 mol P/mol LC 20), indicating that the myosin light chain phosphatase activity was quite high. Mathematical modeling of the kinase and phosphatase reactions suggested that the apparent first-order phosphatase rate constant was at least 0.08 s-1 under these conditions. To obtain a better estimate of this rate constant, a second series of phosphorylation measurements were made early in the relaxation phase of the rhythmic contractions. The highest phosphatase rate constant obtained from these measurements was 0.23 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction between cardiac myosin-binding protein C and formin Fhod3.

Science.gov (United States)

Matsuyama, Sho; Kage, Yohko; Fujimoto, Noriko; Ushijima, Tomoki; Tsuruda, Toshihiro; Kitamura, Kazuo; Shiose, Akira; Asada, Yujiro; Sumimoto, Hideki; Takeya, Ryu

2018-05-08

Mutations in cardiac myosin-binding protein C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C has been considered to regulate the cardiac function via cross-bridge arrangement at the C-zone of the myosin-containing A-band, the mechanism by which cMyBP-C functions remains unclear. We identified formin Fhod3, an actin organizer essential for the formation and maintenance of cardiac sarcomeres, as a cMyBP-C-binding protein. The cardiac-specific N-terminal Ig-like domain of cMyBP-C directly interacts with the cardiac-specific N-terminal region of Fhod3. The interaction seems to direct the localization of Fhod3 to the C-zone, since a noncardiac Fhod3 variant lacking the cMyBP-C-binding region failed to localize to the C-zone. Conversely, the cardiac variant of Fhod3 failed to localize to the C-zone in the cMyBP-C-null mice, which display a phenotype of hypertrophic cardiomyopathy. The cardiomyopathic phenotype of cMyBP-C-null mice was further exacerbated by Fhod3 overexpression with a defect of sarcomere integrity, whereas that was partially ameliorated by a reduction in the Fhod3 protein levels, suggesting that Fhod3 has a deleterious effect on cardiac function under cMyBP-C-null conditions where Fhod3 is aberrantly mislocalized. Together, these findings suggest the possibility that Fhod3 contributes to the pathogenesis of cMyBP-C-related cardiomyopathy and that Fhod3 is critically involved in cMyBP-C-mediated regulation of cardiac function via direct interaction.

The influence of temperature on the distribution and intensity of the reaction product in rat muscle fibers obtained with the histochemical method for myosin ATPase

DEFF Research Database (Denmark)

Kirkeby, S; Tuxen, A

1989-01-01

The influence of temperature in the incubation medium on the localization and intensity of myosin ATPase was investigated in striated muscles from the rat using a conventional histochemical technique. It was found that the enzyme reaction was temperature-dependent since the activity in some fibers...... was raised and in others was depressed by alteration of the incubation temperature. There was no obvious correlation between the temperature sensitivity of ATPase in the muscle fibers and their activity for succinic dehydrogenase. It is proposed that the histochemical method for myosin ATPase can be used...

Development of an indirect counterbalanced pendulum optical-lever thrust balance for micro- to millinewton thrust measurement

International Nuclear Information System (INIS)

Grubišić, A N; Gabriel, S B

2010-01-01

This paper describes the design and testing of an indirect hanging pendulum thrust balance using a laser-optical-lever principle to provide micro- to millinewton thrust measurement for the development of electric propulsion systems. The design philosophy allows the selection of the total thrust range in order to maximize resolution through a counterbalanced pendulum principle, as well as passive magnetic damping in order to allow relatively rapid transient thrust measurement. The balance was designed for the purpose of hollow cathode microthruster characterization, but could be applied to other electric propulsion devices in the thrust range of micro- to millinewtons. An initial thrust characterization of the T5 hollow cathode is presented

Armed conflict and child health.

Science.gov (United States)

Rieder, Michael; Choonara, Imti

2012-01-01

Armed conflict has a major impact on child health throughout the world. One in six children worldwide lives in an area of armed conflict and civilians are more likely to die than soldiers as a result of the conflict. In stark contrast to the effect on children, the international arms trade results in huge profits for the large corporations involved in producing arms, weapons and munitions. Armed conflict is not inevitable but is an important health issue that should be prevented.

[Therapeutic education in pediatric dentistry: analysis of obstacles and levers to the development of programmes in France in 2016].

Science.gov (United States)

Marquillier, Thomas; Trentesaux, Thomas; Gagnayre, Rémi

2017-01-01

Over recent years, therapeutic patient education has become part of dental medicine. Management of early childhood caries, known to be a very common chronic disease, has evolved to include an educational dimension. The objective of this study was to identify the levers and barriers to the development of formalized therapeutic education programmes and alternatives. A comprehensive exploratory qualitative study was conducted between November 2015 and June 2016 on a targeted sample of 15 people aware of the problem of TPE in dentistry. The study showed that TPE training in dentistry is underdeveloped, despite its numerous benefits: change of the healthcare professional's approach, implementation of structured educational programmes, development of research, etc. There are many obstacles to the development of TPE programmes: insufficient resources, rigid legislation or lack of knowledge of TPE practices. The dental profession is an obstacle itself because of its lack of understanding and variable degrees of integration the medical community. There are multiple levers, but the main ones are changing attitudes of the profession and the provision of resources to develop TPE. Although alternatives to TPE programmes exist (accompanying measures, short educational strategies, connected health), they cannot replace TPE. More educational strategies must be developed in the field of dentistry. However, the framework of TPE must be adapted to the profession to ensure good uptake.

Detachment of Tertiary Dendrite Arms during Controlled Directional Solidification in Aluminum - 7 wt Percent Silicon Alloys: Observations from Ground-based and Microgravity Processed Samples

Science.gov (United States)

Grugel, Richard N.; Erdman, Robert; Van Hoose, James R.; Tewari, Surendra; Poirier, David

2012-01-01

Electron Back Scattered Diffraction results from cross-sections of directionally solidified aluminum 7wt% silicon alloys unexpectedly revealed tertiary dendrite arms that were detached and mis-oriented from their parent arm. More surprisingly, the same phenomenon was observed in a sample similarly processed in the quiescent microgravity environment aboard the International Space Station (ISS) in support of the joint US-European MICAST investigation. The work presented here includes a brief introduction to MICAST and the directional solidification facilities, and their capabilities, available aboard the ISS. Results from the ground-based and microgravity processed samples are compared and possible mechanisms for the observed tertiary arm detachment are suggested.

Hello to Arms

Science.gov (United States)

2005-01-01

This image highlights the hidden spiral arms (blue) that were discovered around the nearby galaxy NGC 4625 by the ultraviolet eyes of NASA's Galaxy Evolution Explorer. The image is composed of ultraviolet and visible-light data, from the Galaxy Evolution Explorer and the California Institute of Technology's Digitized Sky Survey, respectively. Near-ultraviolet light is colored green; far-ultraviolet light is colored blue; and optical light is colored red. As the image demonstrates, the lengthy spiral arms are nearly invisible when viewed in optical light while bright in ultraviolet. This is because they are bustling with hot, newborn stars that radiate primarily ultraviolet light. The youthful arms are also very long, stretching out to a distance four times the size of the galaxy's core. They are part of the largest ultraviolet galactic disk discovered so far. Located 31 million light-years away in the constellation Canes Venatici, NGC 4625 is the closest galaxy ever seen with such a young halo of arms. It is slightly smaller than our Milky Way, both in size and mass. However, the fact that this galaxy's disk is forming stars very actively suggests that it might evolve into a more massive and mature galaxy resembling our own. The armless companion galaxy seen below NGC 4625 is called NGC 4618. Astronomers do not know why it lacks arms but speculate that it may have triggered the development of arms in NGC 4625.

Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling

Directory of Open Access Journals (Sweden)

Olga Ossipova

2015-07-01

Full Text Available The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application.

Science.gov (United States)

Pan, Chao-Yu; Kuo, Wei-Ting; Chiu, Chien-Yuan; Lin, Wen-Chang

2017-01-01

MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

Directory of Open Access Journals (Sweden)

Chao-Yu Pan

2017-01-01

Full Text Available MicroRNAs (miRNAs play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

Sensory-Feedback Exoskeletal Arm Controller

Science.gov (United States)

An, Bin; Massie, Thomas H.; Vayner, Vladimir

2004-01-01

An electromechanical exoskeletal arm apparatus has been designed for use in controlling a remote robotic manipulator arm. The apparatus, called a force-feedback exoskeleton arm master (F-EAM) is comfortable to wear and easy to don and doff. It provides control signals from the wearer s arm to a robot arm or a computer simulator (e.g., a virtual-reality system); it also provides force and torque feedback from sensors on the robot arm or from the computer simulator to the wearer s arm. The F-EAM enables the wearer to make the robot arm gently touch objects and finely manipulate them without exerting excessive forces. The F-EAM features a lightweight design in which the motors and gear heads that generate force and torque feedback are made smaller than they ordinarily would be: this is achieved by driving the motors to power levels greater than would ordinarily be used in order to obtain higher torques, and by providing active liquid cooling of the motors to prevent overheating at the high drive levels. The F-EAM (see figure) includes an assembly that resembles a backpack and is worn like a backpack, plus an exoskeletal arm mechanism. The FEAM has five degrees of freedom (DOFs) that correspond to those of the human arm: 1. The first DOF is that of the side-to-side rotation of the upper arm about the shoulder (rotation about axis 1). The reflected torque for this DOF is provided by motor 1 via drum 1 and a planar four-bar linkage. 2. The second DOF is that of the up-and-down rotation of the arm about the shoulder. The reflected torque for this DOF is provided by motor 2 via drum 2. 3. The third DOF is that of twisting of the upper arm about its longitudinal axis. This DOF is implemented in a cable remote-center mechanism (CRCM). The reflected torque for this DOF is provided by motor 3, which drives the upper-arm cuff and the mechanism below it. A bladder inflatable by gas or liquid is placed between the cuff and the wearer s upper arm to compensate for misalignment

Unequal-Arms Michelson Interferometers

Science.gov (United States)

Tinto, Massimo; Armstrong, J. W.

2000-01-01

Michelson interferometers allow phase measurements many orders of magnitude below the phase stability of the laser light injected into their two almost equal-length arms. If, however, the two arms are unequal, the laser fluctuations can not be removed by simply recombining the two beams. This is because the laser jitters experience different time delays in the two arms, and therefore can not cancel at the photo detector. We present here a method for achieving exact laser noise cancellation, even in an unequal-arm interferometer. The method presented in this paper requires a separate readout of the relative phase in each arm, made by interfering the returning beam in each arm with a fraction of the outgoing beam. By linearly combining the two data sets with themselves, after they have been properly time shifted, we show that it is possible to construct a new data set that is free of laser fluctuations. An application of this technique to future planned space-based laser interferometer detector3 of gravitational radiation is discussed.

Knowledge-Oriented Physics-Based Motion Planning for Grasping Under Uncertainty

OpenAIRE

Ud Din, Muhayy; Akbari, Aliakbar; Rosell Gratacòs, Jan

2017-01-01

Grasping an object in unstructured and uncertain environments is a challenging task, particularly when a collision-free trajectory does not exits. High-level knowledge and reasoning processes, as well as the allowing of interaction between objects, can enhance the planning efficiency in such environments. In this direction, this study proposes a knowledge-oriented physics-based motion planning approach for a hand-arm system that uses a high-level knowledge-based reasoning to partition the wor...

Estimation of Lifetime Duration for a Lever Pin of Runner Blade Operating Mechanism using a Graphic – analytic Method

Directory of Open Access Journals (Sweden)

Ana-Maria Budai

2015-09-01

Full Text Available In this paper are presented a graphic - analytic method that can be used to estimate the fatigue lifetime duration for an operating mechanism lever pin to a Kaplan turbine. The presented calculus algorithm is adapted from the one used by Fuji Electric to made strength calculus in order to refurbish a Romanian hydropower plant, equipped with a Kaplan turbine. The graphic part includes a 3D fatigue diagram for rotating bending stress designed by Fuji Electric specialists.

Human Masseter Muscle Fibers From the Elderly Express Less Neonatal Myosin Than Those of Young Adults

Czech Academy of Sciences Publication Activity Database

Cvetko, E.; Karen, Petr; Janáček, Jiří; Kubínová, Lucie; Plasencia, A.L.; Eržen, I.

2012-01-01

Roč. 295, č. 8 (2012), s. 1364-1372 ISSN 1932-8486 R&D Projects: GA MŠk(CZ) LC06063; GA MŠk(CZ) MEB090910 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : aging * confocal microscopy * myosin heavy chain * immunohistochemistry * muscle fiber types Subject RIV: FH - Neurology Impact factor: 1.343, year: 2012

There is plenty of room for motor learning at the bottom of the Fugl-Meyer: Acquisition of a novel bimanual wheelchair skill after chronic stroke using an unmasking technology.

Science.gov (United States)

Sarigul-Klijn, Yasemin; Lobo-Prat, Joan; Smith, Brendan W; Thayer, Sage; Zondervan, Daniel; Chan, Vicky; Stoller, Oliver; Reinkensmeyer, David J

2017-07-01

Many people with a stroke have a severely paretic arm, and it is often assumed that they are unable to learn novel, skilled behaviors that incorporate use of that arm. Here, we show that a group of people with chronic stroke (n = 5, upper extremity Fugl-Meyer scores: 31, 30, 26, 22, 8) learned to use their impaired arm to propel a novel, yoked-clutch lever drive wheelchair. Over six daily training sessions, each involving about 134 training movements with their "useless" arm, the users gradually achieved a 3-fold increase in wheelchair speed on average, with a 4-6 fold increase for three of the participants. They did this by learning a bimanual skill: pushing the levers with both arms while activating the yoked-clutches at the right time with their ipsilesional (i.e. "good") hand to propel the wheelchair forward. They perceived the task as highly motivating and useful. The speed improvements exceeded a 1.5-factor improvement observed when young, unimpaired users learned to propel the chair. The learning rate also exceeded a sample of learning rates from a variety of classic learning studies. These results suggest that appropriately-designed assistive technologies (or "unmasking technologies - UTs") can unleash a powerful, latent ability for motor learning even for severely paretic arms. While UTs may not reduce clinical impairment, they may facilitate large improvements in a specific functional ability.

Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate

Energy Technology Data Exchange (ETDEWEB)

Gomibuchi, Yuki [Graduate School of Science and Engineering, Teikyo University, Toyosatodai 1-1, Utsunomiya 320-8551 (Japan); Uyeda, Taro Q.P. [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, AIST Tsukuba Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan); Wakabayashi, Takeyuki, E-mail: tw007@nasu.bio.teikyo-u.ac.jp [Graduate School of Science and Engineering, Teikyo University, Toyosatodai 1-1, Utsunomiya 320-8551 (Japan); Department of Judo Therapy, Faculty of Medical Technology, Teikyo University, Toyosatodai 1-1, Utsunomiya 320-8551 (Japan)

2013-11-29

Highlights: •The effect of mutation of Tyr143 that becomes more exposed on assembly was examined. •Mutation of tyrosine-143 of Dictyostelium actin changed actin polymerizability. •The bulkiness or aromatic nature of Tyr143 is important for the weak binding. •The weak interaction between myosin and actin strengthened by Tyr143Trp mutation. -- Abstract: Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. By comparing crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine-143 was found to be exposed more than 60 Å{sup 2} to the solvent in F-actin. Because tyrosine-143 flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins were comparable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be reliably compared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (V{sub max}) were estimated by a double reciprocal plot. The Tyr143Trp-actin showed the higher affinity (smaller K{sub app}) than that of the wild-type actin, with the V{sub max} being almost unchanged. The K{sub app} and V{sub max} of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of K{sub app} was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas (ASA

Armed conflict and child health

OpenAIRE

Rieder, Michael; Choonara, Imti

2012-01-01

Armed conflict has a major impact on child health\\ud throughout the world. One in six children worldwide lives\\ud in an area of armed conflict and civilians are more likely\\ud to die than soldiers as a result of the conflict. In stark\\ud contrast to the effect on children, the international arms\\ud trade results in huge profits for the large corporations\\ud involved in producing arms, weapons and munitions.\\ud Armed conflict is not inevitable but is an important\\ud health issue that should be...

β-Arrestin regulation of myosin light chain phosphorylation promotes AT1aR-mediated cell contraction and migration.

Directory of Open Access Journals (Sweden)

Elie Simard

Full Text Available Over the last decade, it has been established that G-protein-coupled receptors (GPCRs signal not only through canonical G-protein-mediated mechanisms, but also through the ubiquitous cellular scaffolds β-arrestin-1 and β-arrestin-2. Previous studies have implicated β-arrestins as regulators of actin reorganization in response to GPCR stimulation while also being required for membrane protrusion events that accompany cellular motility. One of the most critical events in the active movement of cells is the cyclic phosphorylation and activation of myosin light chain (MLC, which is required for cellular contraction and movement. We have identified the myosin light chain phosphatase Targeting Subunit (MYPT-1 as a binding partner of the β-arrestins and found that β-arrestins play a role in regulating the turnover of phosphorylated myosin light chain. In response to stimulation of the angiotensin Type 1a Receptor (AT1aR, MLC phosphorylation is induced quickly and potently. We have found that β-arrestin-2 facilitates dephosphorylation of MLC, while, in a reciprocal fashion, β-arrestin 1 limits dephosphorylation of MLC. Intriguingly, loss of either β-arrestin-1 or 2 blocks phospho-MLC turnover and causes a decrease in the contraction of cells as monitored by atomic force microscopy (AFM. Furthermore, by employing the β-arrestin biased ligand [Sar(1,Ile(4,Ile(8]-Ang, we demonstrate that AT1aR-mediated cellular motility involves a β-arrestin dependent component. This suggests that the reciprocal regulation of MLC phosphorylation status by β-arrestins-1 and 2 causes turnover in the phosphorylation status of MLC that is required for cell contractility and subsequent chemotaxic motility.

Effects of age, sex and arm on the precision of arm position sense—left-arm superiority in healthy right-handers

OpenAIRE

Schmidt, Lena; Depper, Lena; Kerkhoff, Georg

2013-01-01

Position sense is an important proprioceptive ability. Disorders of arm position sense (APS) often occur after unilateral stroke, and are associated with a negative functional outcome. In the present study we assessed horizontal APS by measuring angular deviations from a visually defined target separately for each arm in a large group of healthy subjects. We analyzed the accuracy and instability of horizontal APS as a function of age, sex and arm. Subjects were required to specify verbally th...

Performance of arm locking in LISA

International Nuclear Information System (INIS)

McKenzie, Kirk; Spero, Robert E.; Shaddock, Daniel A.

2009-01-01

For the Laser Interferometer Space Antenna (LISA) to reach its design sensitivity, the coupling of the free-running laser frequency noise to the signal readout must be reduced by more than 14 orders of magnitude. One technique employed to reduce the laser frequency noise will be arm locking, where the laser frequency is locked to the LISA arm length. In this paper we detail an implementation of arm locking. We investigate orbital effects (changing arm lengths and Doppler frequencies), the impact of errors in the Doppler knowledge that can cause pulling of the laser frequency, and the noise limit of arm locking. Laser frequency pulling is examined in two regimes: at lock acquisition and in steady state. The noise performance of arm locking is calculated with the inclusion of the dominant expected noise sources: ultrastable oscillator (clock) noise, spacecraft motion, and shot noise. We find that clock noise and spacecraft motion limit the performance of dual arm locking in the LISA science band. Studying these issues reveals that although dual arm locking [A. Sutton and D. A. Shaddock, Phys. Rev. D 78, 082001 (2008)] has advantages over single (or common) arm locking in terms of allowing high gain, it has disadvantages in both laser frequency pulling and noise performance. We address this by proposing a modification to the dual arm-locking sensor, a hybrid of common and dual arm-locking sensors. This modified dual arm-locking sensor has the laser frequency pulling characteristics and low-frequency noise coupling of common arm locking, but retains the control system advantages of dual arm locking. We present a detailed design of an arm-locking controller and perform an analysis of the expected performance when used with and without laser prestabilization. We observe that the sensor phase changes beneficially near unity-gain frequencies of the arm-locking controller, allowing a factor of 10 more gain than previously believed, without degrading stability. With a time

Using the etalon effect for in situ balancing of the Advanced Virgo arm cavities

International Nuclear Information System (INIS)

Hild, S; Freise, A; Chelkowski, S; Mantovani, M; Degallaix, J; Schilling, R

2009-01-01

Several large-scale interferometric gravitational-wave detectors use resonant arm cavities to enhance the light power in the interferometer arms. These cavities are based on different optical designs: One design uses wedged input mirrors to create additional optical pick-off ports for deriving control signals. The second design employs input mirrors without wedge and thus offers the possibility of using the etalon effect inside the input mirrors for tuning the finesse of the arm cavities. In this paper, we introduce a concept of maximum flexibility that combines both of these options, by featuring wedges at the input mirrors and using the etalon effect instead in the end mirrors. We present a design for the arm cavities of Advanced Virgo. The paper focusses on evaluating the influence of etalon imperfections onto the overall Advanced Virgo performance. We use numerical simulations to derive requirements for the manufacturing accuracy of an end mirror etalon for Advanced Virgo. Furthermore, we give analytical approximations for the achievable tuning range of an imperfect etalon depending on the curvature and orientation mismatch of the two etalon surfaces. We evaluate the displacement noise originating from temperature driven optical phase noise of the etalon. In addition the influence of the etalon effect onto other Advanced Virgo subsystems such as the alignment sensing and control is analysed.

Wave energy, lever operated pivoting float LOPF study

Energy Technology Data Exchange (ETDEWEB)

Margheritini, L.

2012-11-01

The fully instrumented Resen Waves Lever Operated Pivoting Float LOPF wave energy buoy model has gone through the first stage of testing in regular waves in scale 1:25 of the North Sea wave conditions, in the 3D deep wave basin at the Hydraulic and Coastal Engineering Laboratory of Aalborg University in Denmark. The model size was 60cm W x 90cm L x 21cm H. The 60 cm width pointed towards the wave front. The LOPF buoy is characterized by a simple mechanical design with few moving parts and direct electrical output and it is taut moored to the sea bed, so all forces are referenced to the seabed for maximum energy output in regular as well as irregular waves. During storms the buoy pivots and streamlines itself to minimize loads on the mooring line. A conservative estimate shows that a full scale system for North Sea conditions has a float size width of 15 m that will, with 60% generator efficiency, produce 610 MWh/y (609.497 kWh/y) with an average power output of 69.6 kW, which requires a generator capacity of 700 kW. It is expected the generator efficiency can be increased to 90% in the future. More specific calculations (from EnergiNet) show that with one generator of 695 kW the expected power production is 585 MWh/y; with a generator of 250 kW and 100 kW, the expected power production is 481 MWh/y and 182 MWh/y respectively. In addition there are several areas for future improvements for increased power production. (Author)

Design of a multi-arm randomized clinical trial with no control arm.

Science.gov (United States)

Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

2016-01-01

Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

Two-boundary first exit time of Gauss-Markov processes for stochastic modeling of acto-myosin dynamics.

Science.gov (United States)

D'Onofrio, Giuseppe; Pirozzi, Enrica

2017-05-01

We consider a stochastic differential equation in a strip, with coefficients suitably chosen to describe the acto-myosin interaction subject to time-varying forces. By simulating trajectories of the stochastic dynamics via an Euler discretization-based algorithm, we fit experimental data and determine the values of involved parameters. The steps of the myosin are represented by the exit events from the strip. Motivated by these results, we propose a specific stochastic model based on the corresponding time-inhomogeneous Gauss-Markov and diffusion process evolving between two absorbing boundaries. We specify the mean and covariance functions of the stochastic modeling process taking into account time-dependent forces including the effect of an external load. We accurately determine the probability density function (pdf) of the first exit time (FET) from the strip by solving a system of two non singular second-type Volterra integral equations via a numerical quadrature. We provide numerical estimations of the mean of FET as approximations of the dwell-time of the proteins dynamics. The percentage of backward steps is given in agreement to experimental data. Numerical and simulation results are compared and discussed.

Nonspecific Arm Pain

Directory of Open Access Journals (Sweden)

Ali Moradi

2013-12-01

Full Text Available Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Nonspecific Arm Pain

Directory of Open Access Journals (Sweden)

Ali Moradi

2013-12-01

Full Text Available   Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Effects of age, sex and arm on the precision of arm position sense-left-arm superiority in healthy right-handers.

Science.gov (United States)

Schmidt, Lena; Depper, Lena; Kerkhoff, Georg

2013-01-01

Position sense is an important proprioceptive ability. Disorders of arm position sense (APS) often occur after unilateral stroke, and are associated with a negative functional outcome. In the present study we assessed horizontal APS by measuring angular deviations from a visually defined target separately for each arm in a large group of healthy subjects. We analyzed the accuracy and instability of horizontal APS as a function of age, sex and arm. Subjects were required to specify verbally the position of their unseen arm on a 0-90° circuit by comparing the current position with the target position indicated by a LED lamp, while the arm was passively moved by the examiner. Eighty-seven healthy subjects participated in the study, ranging from 20 to 77 years, subdivided into three age groups. The results revealed that APS was not a function of age or sex, but was significantly better in the non-dominant (left) arm in absolute errors (AE) but not in constant errors (CE) across all age groups of right-handed healthy subjects. This indicates a right-hemisphere superiority for left APS in right-handers and neatly fits to the more frequent and more severe left-sided body-related deficits in patients with unilateral stroke (i.e. impaired APS in left spatial neglect, somatoparaphrenia) or in individuals with abnormalities of the right cerebral hemisphere. These clinical issues will be discussed.

Reflective practices at the Security Council: Children and armed conflict and the three United Nations.

Science.gov (United States)

Bode, Ingvild

2018-06-01

The United Nations Security Council passed its first resolution on children in armed conflict in 1999, making it one of the oldest examples of Security Council engagement with a thematic mandate and leading to the creation of a dedicated working group in 2005. Existing theoretical accounts of the Security Council cannot account for the developing substance of the children and armed conflict agenda as they are macro-oriented and focus exclusively on states. I argue that Security Council decision-making on thematic mandates is a productive process whose outcomes are created by and through practices of actors across the three United Nations: member states (the first United Nations), United Nations officials (the second United Nations) and non-governmental organizations (the third United Nations). In presenting a practice-based, micro-oriented analysis of the children and armed conflict agenda, the article aims to deliver on the empirical promise of practice theories in International Relations. I make two contributions to practice-based understandings: first, I argue that actors across the three United Nations engage in reflective practices of a strategic or tactical nature to manage, arrange or create space in Security Council decision-making. Portraying practices as reflective rather than as only based on tacit knowledge highlights how actors may creatively adapt their practices to social situations. Second, I argue that particular individuals from the three United Nations are more likely to become recognized as competent performers of practices because of their personality, understood as plural socialization experiences. This adds varied individual agency to practice theories that, despite their micro-level interests, have focused on how agency is relationally constituted.

A Descriptive Study of Lower Limb Torsional Kinematic Profiles in Children With Spastic Diplegia.

Science.gov (United States)

Simon, Anne-Laure; Ilharreborde, Brice; Megrot, Fabrice; Mallet, Cindy; Azarpira, Reza; Mazda, Keyvan; Presedo, Ana; Penneçot, Georges F

2015-09-01

Lower limb rotational anomalies in spastic diplegic children with cerebral palsy (CP) are common and difficult to identify through physical examination alone. The identification and treatment of the overall rotational disorders must be considered to restore physiological lever-arms lengths and lever-arms orientation.The aims of the study were to assess the prevalence of lower limb rotational malalignment and to describe the distribution of the different kinematic torsional profiles in children with spastic diplegia. Instrumented gait analysis data from 188 children with spastic diplegia were retrospectively reviewed. None of the patients had undergone surgery previously or received botulinum toxin treatment within 6 months before the review. Kinematic data, collected at the midstance phase, included: pelvic, hip, and ankle rotation and foot progression angle. The prevalence of kinematic rotational deviations was 98.4%. Sixty-one percent of the children walked with an internal foot progression angle and 21% exhibited external alignment. The pelvis was internally rotated in 41% of the cases and externally in another 27%. Hip rotation was internal in 29% and external in 27% of the cases. Ankle rotation was internal in 55% and external in 16% of the cases. Lower limb rotational anomalies involved more than one level in 77% of the limbs. A kinematic compensatory deviation was identified in at least one level in 48% of the limbs. Kinematic rotational anomalies were identified in nearly all the 188 children in the study. The multilevel involvement of lower limb malalignment was not systematically associated with compensatory mechanisms between the levels. Ankle rotational anomalies were the most frequent cause of lower limb torsional deviations followed by pelvic malalignment. Level IV.

Conformational distributions and proximity relationships in the rigor complex of actin and myosin subfragment-1.

Science.gov (United States)

Nyitrai, M; Hild, G; Lukács, A; Bódis, E; Somogyi, B

2000-01-28

Cyclic conformational changes in the myosin head are considered essential for muscle contraction. We hereby show that the extension of the fluorescence resonance energy transfer method described originally by Taylor et al. (Taylor, D. L., Reidler, J., Spudich, J. A., and Stryer, L. (1981) J. Cell Biol. 89, 362-367) allows determination of the position of a labeled point outside the actin filament in supramolecular complexes and also characterization of the conformational heterogeneity of an actin-binding protein while considering donor-acceptor distance distributions. Using this method we analyzed proximity relationships between two labeled points of S1 and the actin filament in the acto-S1 rigor complex. The donor (N-[[(iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonate) was attached to either the catalytic domain (Cys-707) or the essential light chain (Cys-177) of S1, whereas the acceptor (5-(iodoacetamido)fluorescein) was attached to the actin filament (Cys-374). In contrast to the narrow positional distribution (assumed as being Gaussian) of Cys-707 (5 +/- 3 A), the positional distribution of Cys-177 was found to be broad (102 +/- 4 A). Such a broad positional distribution of the label on the essential light chain of S1 may be important in accommodating the helically arranged acto-myosin binding relative to the filament axis.

Arms control and disarmament

International Nuclear Information System (INIS)

Acton, P.

1992-01-01

Article VI of the Non-Proliferation Treaty commits each party to work towards nuclear disarmament and to negotiations to stop the nuclear arms race. All parties to the Treaty are included and a wide range of arms control and disarmament issues are covered. However the main focus at Treaty review conferences has been on nuclear disarmament by the nuclear weapon states which are party to the Treaty. This has led to bilateral United States - Soviet Union negotiations resulting in the Intermediate-range Nuclear Forces Treaty in December 1987 and the Strategic Arms Reduction Treaty (START) in July followed by unilateral arms control measures in September and October 1991. (UK)

Masticatory muscle architecture in a water-rat from Australasia (Murinae, Hydromys) and its implication for the evolution of carnivory in rodents.

Science.gov (United States)

Fabre, P-H; Herrel, A; Fitriana, Y; Meslin, L; Hautier, L

2017-09-01

Murines are well known for their generalist diet, but several of them display specializations towards a carnivorous diet such as the amphibious Indo-Pacific water-rats. Despite the fact that carnivory evolved repeatedly in this group, few studies have investigated associated changes in jaw muscle anatomy and biomechanics. Here, we describe the jaw muscles and cranial anatomy of a carnivorous water-rat, Hydromys chrysogaster. The architecture of the jaw musculature of six specimens captured both on Obi and Papua were studied and described using dissections. We identified the origin and insertions of the jaw muscles, and quantified muscle mass, fiber length, physiological cross-sectional area, and muscle vectors for each muscle. Using a biomechanical model, we estimated maximum incisor and molar bite force at different gape angles. Finally, we conducted a 2D geometric morphometric analyses to compare jaw shape, mechanical potential, and diversity in lever-arm ratios for a set of 238 specimens, representative of Australo-Papuan carnivorous and omnivorous murids. Our study reveals major changes in the muscle proportions among Hydromys and its omnivorous close relative, Melomys. Hydromys was found to have large superficial masseter and temporalis muscles as well as a reduced deep masseter and zygomatico-mandibularis, highlighting major functional divergence among omnivorous and carnivorous murines. Changes in these muscles are also accompanied by changes in jaw shape and the lines of action of the muscles. A more vertically oriented masseter, reduced masseteric muscles, as well as an elongated jaw with proodont lower incisors are key features indicative of a reduced propalinality in carnivorous Hydromys. Differences in the fiber length of the masseteric muscles were also detected between Hydromys and Melomys, which highlight potential adaptations to a wide gape in Hydromys, allowing it to prey on larger animals. Using a biomechanical model, we inferred a greater bite

Effects of nucleus accumbens core and shell lesions on autoshaped lever-pressing.

Science.gov (United States)

Chang, Stephen E; Holland, Peter C

2013-11-01

Certain Pavlovian conditioned stimuli (CSs) paired with food unconditioned stimuli (USs) come to elicit approach and even consumption-like behaviors in rats (sign-tracking). We investigated the effects of lesions of the nucleus accumbens core (ACbC) or shell (ACbS) on the acquisition of sign-tracking in a discriminative autoshaping procedure in which presentation of one lever CS was followed by delivery of sucrose, and another was not. Although we previously found that bilateral lesions of the whole ACb disrupted the initial acquisition of sign-tracking, neither ACbC or ACbS lesions affected the rate or percentage of trials in which rats pressed the CS+. In addition, detailed video analysis showed no effect of either lesion on the topography of the sign-tracking conditioned response (CR). These and other results from lesion studies of autoshaping contrast with those from previous sign-tracking experiments that used purely visual cues (Parkinson et al., 2000a,b), suggesting that the neural circuitry involved in assigning incentive value depends upon the nature of the CS. Copyright © 2013 Elsevier B.V. All rights reserved.

[Psychiatric, Cognitive and Emotional Profile in Ex-combatants of Illegal Armed Groups in Colombia].

Science.gov (United States)

Tobón, Carlos; Aguirre-Acevedo, Daniel Camilo; Velilla, Lina; Duque, Jon; Ramos, Claudia Patricia; Pineda, David

2016-01-01

Exposure to armed conflict produces biological adaptations oriented to handle the highly stressful conditions in war environments. The special features of The Colombian armed create a special scenario to evaluate the human behavior. In this study, psychiatric, cognitive and emotional processing characteristics of a group of Colombian armed illegal forces of ex-combatants are described. Sixty-three ex combatants and 22 controls were assessed with WAIS (IQ), INECO frontal screening (executive functions), Interpersonal Reactivity Index (empathy), emotional features recognition and MINI (psychiatric profile). When compared to the control group, ex-combatants showed higher frequency of antisocial personality disorder (P=.031) and behavioral dissocial disorder (P=.017). In cognitive profile, the ex-combatants showed a lower score in the executive function test (Me=18.50; RQ=4.00), control (Me=23.00; RQ=5.25), with a poor personal distress in emphatic profile (Me=10.00; RQ=5.00) compared to control group (Me=37.00; RQ=7.25). We found differences in cognitive and psychiatric profile in ex-combatants in comparison with controls. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Pesquisa de marcadores para os genes da cadeia pesada da beta-miosina cardíaca e da proteína C de ligação à miosina em familiares de pacientes com cardiomiopatia hipertrófica Research of markers for the genes of the heavy chain of cardiac beta-myosin and myosin binding protein C in relatives of patients with hypertrophic cardiomyopathy

Directory of Open Access Journals (Sweden)

Adriana Paula Tirone

2005-06-01

Full Text Available OBJETIVO: Estudar os marcadores moleculares para os genes da cadeia pesada da beta-miosina cardíaca e da proteína-C de ligação à miosina em familiares de portadores de cardiomiopatia hipertrófica. MÉTODOS: Foram estudadas 12 famílias que realizaram anamnese, exame físico, eletrocardiograma, ecocardiograma e coleta de sangue para o estudo genético através da reação em cadeia da polimerasse. RESULTADOS: Dos 227 familiares 25% eram acometidos, sendo 51% do sexo masculino com idade média de 35±19 (2 a 95 anos. A análise genética mostrou ligação com o gene da b-miosina cardíaca em uma família e, em outra, ligação com o gene da proteína C de ligação à miosina. Em cinco famílias foram excluídas ligações com os dois genes; em duas, a ligação com o gene da proteína C de ligação à miosina, porém para o gene da b-miosina os resultados foram inconclusivos; em duas famílias os resultados foram inconclusivos para os dois genes e em uma foi excluída ligação para o gene da b-miosina mas ficou inconclusivo para o gene da proteína C de ligação à miosina. CONCLUSÃO: Em nosso meio, talvez predominem outros genes que não aqueles descritos na literatura, ou que existam outras diferenças genéticas relacionadas com a origem de nossa população e/ou fatores ambientais.OBJECTIVE: To study the molecular markers for the genes of the heavy chain of cardiac beta-myosin and the myosin binding protein C in relatives of carriers of hypertrophic cardiomyopathy. METHODS: Twelve families who had anamnesis, physical exam, electrocardiogram, echocardiogram and blood collection for the genetic study through the chain reaction of polymerase. RESULTS: From the 227 relatives, 25% were ill-taken, with 51% men, with an average age of 35±19 (2 to 95 years old. The genetic analysis showed a connection with the gene of the cardiac b-myosin in a family and, in another, a connection with the gene of the myosin-binding protein C. In five

Musculoskeletal modelling of an ostrich (Struthio camelus pelvic limb: influence of limb orientation on muscular capacity during locomotion

Directory of Open Access Journals (Sweden)

John R. Hutchinson

2015-06-01

Full Text Available We developed a three-dimensional, biomechanical computer model of the 36 major pelvic limb muscle groups in an ostrich (Struthio camelus to investigate muscle function in this, the largest of extant birds and model organism for many studies of locomotor mechanics, body size, anatomy and evolution. Combined with experimental data, we use this model to test two main hypotheses. We first query whether ostriches use limb orientations (joint angles that optimize the moment-generating capacities of their muscles during walking or running. Next, we test whether ostriches use limb orientations at mid-stance that keep their extensor muscles near maximal, and flexor muscles near minimal, moment arms. Our two hypotheses relate to the control priorities that a large bipedal animal might evolve under biomechanical constraints to achieve more effective static weight support. We find that ostriches do not use limb orientations to optimize the moment-generating capacities or moment arms of their muscles. We infer that dynamic properties of muscles or tendons might be better candidates for locomotor optimization. Regardless, general principles explaining why species choose particular joint orientations during locomotion are lacking, raising the question of whether such general principles exist or if clades evolve different patterns (e.g., weighting of muscle force–length or force–velocity properties in selecting postures. This leaves theoretical studies of muscle moment arms estimated for extinct animals at an impasse until studies of extant taxa answer these questions. Finally, we compare our model’s results against those of two prior studies of ostrich limb muscle moment arms, finding general agreement for many muscles. Some flexor and extensor muscles exhibit self-stabilization patterns (posture-dependent switches between flexor/extensor action that ostriches may use to coordinate their locomotion. However, some conspicuous areas of disagreement in our

[Stigma and Mental Health in Victims of Colombia's Internal Armed Conflict in Situation of Forced Displacement].

Science.gov (United States)

Campo-Arias, Adalberto; Herazo, Edwin

2014-01-01

The prolonged sociopolitical phenomenon of Colombian violence generated a high number of victims, many of whom suffered a continual process of internal displacement and stigma-discrimination complex. To postulate possible mechanisms by which victims of Colombia's internal armed conflict in a situation of forced displacement were stigmatized and discriminated. Stigma affects mental health, not only because it represents a major stressor for discriminated individuals and groups, but also because it accounts for inequalities and inequities in health. Initially, as the victims of the internal armed conflict in situation of forced displacement were not considered as such, but as responsible for the situation. Thus, they had to cope with the social and economic inequalities, explained partially by low categorization or status that they received, possibly due to poor construction of social capital in the country. Also, victims of the internal armed conflict suffer from intersectional stigma and discrimination due to other characteristics such as gender, sexual orientation, ethnic-racial origin, or meeting criteria for a mental disorder. An active process of inclusive social development is required for the displaced victims of the armed conflict,in order to reduce multiple stigma and ensure their mental health. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Understanding the conventional arms trade

Science.gov (United States)

Stohl, Rachel

2017-11-01

The global conventional arms trade is worth tens of billions of dollars every year and is engaged in by every country in the world. Yet, it is often difficult to control the legal trade in conventional arms and there is a thriving illicit market, willing to arm unscrupulous regimes and nefarious non-state actors. This chapter examines the international conventional arms trade, the range of tools that have been used to control it, and challenges to these international regimes.

Use of the ARM Measurements of Spectral Zenith Radiance for Better Understanding of 3D Cloud-Radiation Processes & Aerosol-Cloud Interaction

Energy Technology Data Exchange (ETDEWEB)

Alexander Marshak; Warren Wiscombe; Yuri Knyazikhin; Christine Chiu

2011-05-24

We proposed a variety of tasks centered on the following question: what can we learn about 3D cloud-radiation processes and aerosol-cloud interaction from rapid-sampling ARM measurements of spectral zenith radiance? These ARM measurements offer spectacular new and largely unexploited capabilities in both the temporal and spectral domains. Unlike most other ARM instruments, which average over many seconds or take samples many seconds apart, the new spectral zenith radiance measurements are fast enough to resolve natural time scales of cloud change and cloud boundaries as well as the transition zone between cloudy and clear areas. In the case of the shortwave spectrometer, the measurements offer high time resolution and high spectral resolution, allowing new discovery-oriented science which we intend to pursue vigorously. Research objectives are, for convenience, grouped under three themes: • Understand radiative signature of the transition zone between cloud-free and cloudy areas using data from ARM shortwave radiometers, which has major climatic consequences in both aerosol direct and indirect effect studies. • Provide cloud property retrievals from the ARM sites and the ARM Mobile Facility for studies of aerosol-cloud interactions. • Assess impact of 3D cloud structures on aerosol properties using passive and active remote sensing techniques from both ARM and satellite measurements.

STEM-based workbook: Enhancing students' STEM competencies on lever system

Science.gov (United States)

Sejati, Binar Kasih; Firman, Harry; Kaniawati, Ida

2017-05-01

Twenty-first century is a century of technology, a rapid development of scientific studies and technology make them relied heavily on each other. This research investigated about the effect of STEM-based workbook in enhancing students' STEM competencies in terms of knowledge understanding, problem solving skill, innovative abilities, and responsibility. The workbook was tried on 24 students that applied engineering design processes together with mathematics and science knowledge to design and create an egg cracker. The result showed that the implementation of STEM-based workbook on lever system in human body is effective to improve students' STEM competencies, it can be proven by students' result on their knowledge understanding improvement which can be seen from normalized gain () score is 0.41 and categorized as medium improvement, students' problem solving skill is also improving where it obtained a medium improvement with normalized gain as much as 0.45. Innovative abilities also encountered an the improvement, the workbook analysis obtained a higher score which means students can be more innovative after finishing their workbook. Last, students' responsibility is keep improving day by day, students' effort gain the highest score it means that the students become more responsible after implementation of STEM-based workbook. All of the results are supported with the response of students towards STEM-based workbook implementation which showed positive response in all indicators.

Contractile properties, fiber types, and myosin isoforms in fast and slow muscles of hyperactive Japanese waltzing mice

Czech Academy of Sciences Publication Activity Database

Asmussen, G.; Schmalbruch, I.; Soukup, Tomáš; Pette, D.

2003-01-01

Roč. 184, č. 2 (2003), s. 758-766 ISSN 0014-4886 R&D Projects: GA ČR GA304/00/1653 Grant - others:Deutsche Forschungsgemeinschaft(DE) -; Sonderforschungsbereich(DE) 156; Schwerpunkt Muskelforschung(DE) As 74/1-2 Institutional research plan: CEZ:AV0Z5011922 Keywords : Japanese waltzing mouse * muscle contraction * myosin isoforms Subject RIV: ED - Physiology Impact factor: 3.676, year: 2003

An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

NARCIS (Netherlands)

Schneeberger, Kerstin; Vogel, Georg F; Teunissen, Hans; van Ommen, Domenique D; Begthel, Harry; El Bouazzaoui, Layla; van Vugt, Anke H M; Beekman, Jeffrey M; Klumperman, Judith; Müller, Thomas; Janecke, Andreas; Gerner, Patrick; Huber, Lukas A; Hess, Michael W; Clevers, Hans; van Es, Johan H; Nieuwenhuis, Edward E S; Middendorp, Sabine

2015-01-01

Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with an onset within a few days to months after birth, resulting in persistent watery diarrhea. Mutations in the myosin Vb gene (MYO5B) have been identified in the majority of MVID patients. However, the exact pathophysiology of

Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform

Directory of Open Access Journals (Sweden)

Yi Ting

2012-11-01

Full Text Available Abstract It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG and that exposure of zinc ion (Zn2+ to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our

Student measurement of blood pressure using a simulator arm compared with a live subject's arm.

Science.gov (United States)

Lee, Jennifer J; Sobieraj, Diana M; Kuti, Effie L

2010-06-15

To compare accuracy of blood pressure measurements using a live subject and a simulator arm, and to determine students' preferences regarding measurement. This was a crossover study comparing blood pressure measurements from a live subject and a simulator arm. Students completed an anonymous survey instrument defining opinions on ease of measurement. Fifty-seven students completed blood pressure measurements on live subjects while 72 students completed blood pressure measurements using the simulator arm. There were no significant systematic differences between the 2 measurement techniques. Systolic blood pressure measurements from a live subject arm were less likely to be within 4 mm Hg compared with measurements of a simulator arm. Diastolic blood pressure measurements were not significantly different between the 2 techniques. Accuracy of student measurement of blood pressure using a simulator arm was similar to the accuracy with a live subject. There was no difference in students' preferences regarding measurement techniques.

LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring.

Science.gov (United States)

Price, Kari L; Rose, Lesilee S

2017-09-01

The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the Caenorhabditis elegans one-cell embryo, the astral microtubule-dependent pathway requires anillin, NOP-1, and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division. However, whether the role of LET-99 in cytokinesis is specific to asymmetric division and whether it acts through Gα to promote furrowing are unclear. Here we show that LET-99 contributes to furrowing in both asymmetrically and symmetrically dividing cells, independent of its function in spindle positioning and Gα regulation. LET-99 acts in a pathway parallel to anillin and is required for myosin enrichment into the contractile ring. These and other results suggest a positive feedback model in which LET-99 localizes to the presumptive cleavage furrow in response to the spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to promote furrowing in both symmetrically and asymmetrically dividing cells. © 2017 Price and Rose. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Dependence of myosin-ATPase on structure bound creatine kinase in cardiac myfibrils from rainbow trout and freshwater turtle

DEFF Research Database (Denmark)

Haagensen, L.; Jensen, D.H.; Gesser, Hans

2008-01-01

The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP by the pyr......The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP...... by the pyruvate kinase reaction alone or together with the amount of creatine formed, when myofibrillar bound creatine kinase was activated with phosphocreatine. The steady-state concentration of ADP in the solution was varied through the activity of pyruvate kinase added to the solution. For rainbow trout...... myofibrils at a high pyruvate kinase activity, creatine kinase competed for ADP but did not influence the total ATPase activity. When the ADP concentration was elevated within the physiological range by lowering the pyruvate kinase activity, creatine kinase competed efficiently and increased the ATPase...

Borehole tool outrigger arm displacement control mechanism

International Nuclear Information System (INIS)

Lee, A.G.

1985-01-01

As the outrigger arms of a borehole logging tool are flexed inwardly and outwardly according to the diameter of the borehole opening through which they pass, the corresponding axial displacements of the ends of the arms are controlled to determine the axial positions of the arms relative to the tool. Specifically, as the arm ends move, they are caused to rotate by a cam mechanism. The stiffness of the arms causes the arm ends to rotate in unison, and the exact positions of the arms on the tool are then controlled by the differential movements of the arm ends in the cams

Nonparetic arm force does not overinhibit the paretic arm in chronic poststroke hemiparesis.

Science.gov (United States)

Dimyan, Michael A; Perez, Monica A; Auh, Sungyoung; Tarula, Erick; Wilson, Matthew; Cohen, Leonardo G

2014-05-01

To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis. Case-control neurophysiological and behavioral study of patients with chronic stroke. Research institution. Eighty-six referred patients were screened to enroll 9 participants (N=9) with a >6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation. Eight age- and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison. Not applicable. Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis. Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario (20%±7% vs -1%±4%, F1,12=6.61, P=.025). Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

NARCIS (Netherlands)

Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

2016-01-01

Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen

Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle.

Science.gov (United States)

Pandorf, Clay E; Jiang, Weihua; Qin, Anqi X; Bodell, Paul W; Baldwin, Kenneth M; Haddad, Fadia

2012-04-01

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.

Mechanical Defects of Muscle Fibers with Myosin Light Chain Mutants that Cause Cardiomyopathy

OpenAIRE

Roopnarine, Osha

2003-01-01

Familial hypertrophic cardiomyopathy is a disease caused by single mutations in several sarcomeric proteins, including the human myosin ventricular regulatory light chain (vRLC). The effects of four of these mutations (A13T, F18L, E22K, and P95A) in vRLC on force generation were determined as a function of Ca2+ concentration. The endogenous RLC was removed from skinned rabbit psoas muscle fibers, and replaced with either rat wildtype vRLC or recombinant rat vRLC (G13T, F18L, E22K, and P95A). ...

Prediction of bed level variations in nonuniform sediment bed channel

Indian Academy of Sciences (India)

B R Andharia

2018-04-12

Apr 12, 2018 ... A fully-coupled 1D mobile-bed model (CAR-. ICHAR) was introduced ...... for sediment trap, water level sensor, tail gate operated by lever arm at .... materials were brought back to upstream to feed the same through sediment ...

Nature of galaxy spiral arms

International Nuclear Information System (INIS)

Efremov, Yu.N.

1984-01-01

The nature of galaxy spiral arms is discussed in a popular form. Two approaches in the theory of spiral arms are considered; they are related to the problem of differential galaxy rotation and the spiral structure wave theory. The example of Galaxy M31 is considered to compare the structural peculiarity of its spiral arms with the wave theory predictions. The situation in the central and south-eastern part of arm S4 in Galaxy M31 noted to be completely explained by the wave theory and modern concepts on the origin of massive stars

Arms races between and within species.

Science.gov (United States)

Dawkins, R; Krebs, J R

1979-09-21

An adaptation in one lineage (e.g. predators) may change the selection pressure on another lineage (e.g. prey), giving rise to a counter-adaptation. If this occurs reciprocally, an unstable runaway escalation or 'arms race' may result. We discuss various factors which might give one side an advantage in an arms race. For example, a lineage under strong selection may out-evolve a weakly selected one (' the life-dinner principle'). We then classify arms races in two independent ways. They may be symmetric or asymmetric, and they may be interspecific or intraspecific. Our example of an asymmetric interspecific arms race is that between brood parasites and their hosts. The arms race concept may help to reduce the mystery of why cuckoo hosts are so good at detecting cuckoo eggs, but so bad at detecting cuckoo nestlings. The evolutionary contest between queen and worker ants over relative parental investment is a good example of an intraspecific asymmetric arms race. Such cases raise special problems because the participants share the same gene pool. Interspecific symmetric arms races are unlikely to be important, because competitors tend to diverge rather than escalate competitive adaptations. Intraspecific symmetric arms races, exemplified by adaptations for male-male competition, may underlie Cope's Rule and even the extinction of lineages. Finally we consider ways in which arms races can end. One lineage may drive the other to extinction; one may reach an optimum, thereby preventing the other from doing so; a particularly interesting possibility, exemplified by flower-bee coevolution, is that both sides may reach a mutual local optimum; lastly, arms races may have no stable and but may cycle continuously. We do not wish necessarily to suggest that all, or even most, evolutionary change results from arms races, but we do suggest that the arms race concept may help to resolve three long-standing questions in evolutionary theory.

JPRS Report Arms Control

National Research Council Canada - National Science Library

1993-01-01

Table of Contents: (1) COMMONWEALTH OF INDEPENDENT STATES - (A) GENERAL Flaws in U.S.-Russian SSD Agreement Viewed, Khariton - Espionage Not Crucial in Soviet Nuclear Arms Development, Further on Espionage Role in Nuclear Arms Projects...

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

Science.gov (United States)

Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

2013-11-01

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

Content of conventional therapy for the severely affected arm during subacute rehabilitation after stroke: An analysis of physiotherapy and occupational therapy practice.

Science.gov (United States)

de Jong, Lex D; van Wijck, Frederike; Stewart, Roy E; Geurts, Alexander C H; Dijkstra, Pieter U

2018-01-01

Physiotherapy (PT) and occupational therapy (OT) are key professions providing treatment for the arm after stroke; however, knowledge about the content of these treatments is scant. Detailed data are needed to replicate interventions, evaluate their effective components, and evaluate PT and OT practice. This paper describes PT and OT treatment for the severely affected arm in terms of duration, content according to components and categories of the International Classification of Human Functioning, Disability and Health, and to analyze differences between professions. Design: This is a retrospective analysis of randomized trial data. 46 patients after stroke with poor arm motor control recruited from inpatient neurological units from three rehabilitation centers in the Netherlands. PTs and OTs recorded duration and content of arm treatment interventions for 8 weeks using a bespoke treatment schedule with 15 International Classification of Human Functioning, Disability and Health categories. PTs and OTs spent on average 4-7 min per treatment session (30 min) on arm treatment. OTs spent significantly more time providing arm treatment and treatment at the activities level than PTs. PTs spent 79% of their arm treatment time on body functions, OTs 41%. OTs spent significantly more time on "moving around using transportation," "self care," and "household tasks" categories. Patients after stroke with a severely affected arm and an unfavorable prognosis for arm motor recovery receive little arm-oriented PT and OT. Therapists spent most arm treatment time on body functions. There was a considerable overlap in the content of PT and OT in 12 of the 15 categories. Results can be generalized only to patients with poor arm motor control and may not represent practice in other countries. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of psychotropic agents on extinction of lever-press avoidance in a rat model of anxiety vulnerability

Directory of Open Access Journals (Sweden)

Xilu eJiao

2014-09-01

Full Text Available Avoidance and its perseveration represent key features of anxiety disorders. Both pharmacological and behavioral approaches (i.e. anxiolytics and extinction therapy have been utilized to modulate avoidance behavior in patients. However, the outcome has not always been desirable. Part of the reason is attributed to the diverse neuropathology of anxiety disorders. Here, we investigated the effect of psychotropic drugs that target various monoamine systems on extinction of avoidance behavior using lever-press avoidance task. Here we used the Wistar-Kyoto (WKY rat, a unique rat model that exhibits facilitated avoidance and extinction resistance along with malfunction of the dopamine (DA system. Sprague Dawley (SD and WKY rats were trained to acquire lever-press avoidance. WKY rats acquired avoidance faster and to a higher level compared to SD rats. During pharmacological treatment, bupropion, and desipramine significantly reduced avoidance response selectively in WKY rats. However, after the discontinuation of drug treatment, only those WKY rats that were previously treated with desipramine exhibited lower avoidance response compared to the control group. In contrast, none of the psychotropic drugs facilitated avoidance extinction in SD rats. Instead, desipramine impaired avoidance extinction and increased non-reinforced response in SD rats. Interestingly, paroxetine, a widely used antidepressant and anxiolytic, exhibited the weakest effect in WKY rats and no effects at all in SD rats. Thus, our data suggest that malfunctions in brain catecholamine system could be one of the underlying etiologies of anxiety-like behavior, particularly avoidance perseveration. Pharmacological manipulation targeting DA and norepinephrine is more effective to facilitate extinction learning in this strain. The data from the present study may shed light on new pharmacological approaches to treat patients with anxiety disorders who are not responding to serotonin re

Organization of octopus arm movements: a model system for studying the control of flexible arms.

Science.gov (United States)

Gutfreund, Y; Flash, T; Yarom, Y; Fiorito, G; Segev, I; Hochner, B

1996-11-15

Octopus arm movements provide an extreme example of controlled movements of a flexible arm with virtually unlimited degrees of freedom. This study aims to identify general principles in the organization of these movements. Video records of the movements of Octopus vulgaris performing the task of reaching toward a target were studied. The octopus extends its arm toward the target by a wave-like propagation of a bend that travels from the base of the arm toward the tip. Similar bend propagation is seen in other octopus arm movements, such as locomotion and searching. The kinematics (position and velocity) of the midpoint of the bend in three-dimensional space were extracted using the direct linear transformation algorithm. This showed that the bend tends to move within a single linear plane in a simple, slightly curved path connecting the center of the animal's body with the target location. Approximately 70% of the reaching movements demonstrated a stereotyped tangential velocity profile. An invariant profile was observed when movements were normalized for velocity and distance. Two arms, extended together in the same behavioral context, demonstrated identical velocity profiles. The stereotyped features of the movements were also observed in spontaneous arm extensions (not toward an external target). The simple and stereotypic appearance of the bend trajectory suggests that the position of the bend in space and time is the controlled variable. We propose that this strategy reduces the immense redundancy of the octopus arm movements and hence simplifies motor control.

Neuromuscular partitioning, architectural design, and myosin fiber types of the M. vastus lateralis of the llama (Lama glama).

Science.gov (United States)

Graziotti, Guillermo H; Palencia, Pablo; Delhon, Gustavo; Rivero, José-Luis L

2004-11-01

The llama (Lama glama) is one of the few mammals of relatively large body size in which three fast myosin heavy chain isoforms (i.e., IIA, IIX, IIB) are extensively expressed in their locomotory muscles. This study was designed to gain insight into the morphological and functional organization of skeletal musculature in this peculiar animal model. The neuromuscular partitioning, architectural design, and myosin fiber types were systematically studied in the M. vastus lateralis of adult llamas (n = 15). Four nonoverlapping neuromuscular partitions or compartments were identified macroscopically (using a modified Sihler's technique for muscle depigmentation), although they did not conform strictly to the definitions of "neuromuscular compartments." Each neuromuscular partition was innervated by primary branches of the femoral nerve and was arranged within the muscle as paired partitions, two in parallel (deep-superficial compartmentalization) and the other two in-series (proximo-distal compartmentalization). These neuromuscular partitions of the muscle varied in their respective architectural designs (studied after partial digestion with diluted nitric acid) and myosin fiber type characteristics (identified immunohistochemically with specific anti-myosin monoclonal antibodies, then examined by quantitative histochemistry and image analysis). The deep partitions of the muscle had longer fibers, with lower angles of pinnation, and higher percentages of fast-glycolytic fibers than the superficial partitions of the muscle. These differences clearly suggest a division of labor in the whole M. vastus lateralis of llamas, with deep partitions exhibiting features well adapted for dynamic activities in the extension of stifle, whereas superficial portions seem to be related to the antigravitational role of the muscle in preserving the extension of the stifle during standing and stance phase of the stride. This peculiar structural and functional organization of the llama M

A collapsin response mediator protein 2 isoform controls myosin II-mediated cell migration and matrix assembly by trapping ROCK II

DEFF Research Database (Denmark)

Yoneda, Atsuko; Morgan-Fisher, Marie; Wait, Robin

2012-01-01

Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among...... nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two......-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions...

High precision detector robot arm system

Science.gov (United States)

Shu, Deming; Chu, Yong

2017-01-31

A method and high precision robot arm system are provided, for example, for X-ray nanodiffraction with an X-ray nanoprobe. The robot arm system includes duo-vertical-stages and a kinematic linkage system. A two-dimensional (2D) vertical plane ultra-precision robot arm supporting an X-ray detector provides positioning and manipulating of the X-ray detector. A vertical support for the 2D vertical plane robot arm includes spaced apart rails respectively engaging a first bearing structure and a second bearing structure carried by the 2D vertical plane robot arm.

Algorithms for Unequal-Arm Michelson Interferometers