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PubMed1995

Impairments of reaching movements in patients without proprioception. I. Spatial errors.

1. This paper introduces a series of studies in which we analyze the impairments in a planar reaching task in human patients with severe proprioceptive deficits resulting from large-fiber sensory neuropathy. We studied three patients, all of whom showed absence of discriminative tactile sensation, position sense, and stretch reflexes in the upper extremities. Muscle strength was normal. We compared the reaching movements of the patients with those of normal control subjects. The purpose of this first paper was no characterize the spatial errors in these patients that result primarily from impairments in the planning and execution of movement rather than in feedback control. This was done by using a task in which visual feedback of errors during movement was prevented. 2. Subjects were instructed to move their hand from given starting positions of different targets on a horizontal digitizing tablet. Hand position and targets were displayed on a computer screen. Subjects could not see their hand, and the screen display of hand position was blanked at the signal to move. Thus visual feedback during movement could not be used to achieve accuracy. Movement paths were displayed as knowledge of results after each trial. 3. Compared with controls, the patients made large spatial errors in both movement direction and extent. Directional errors were evident from movement onset, suggesting that they resulted from improper planning. In addition, patients' hand paths showed large curves and secondary movements after initial stops. 4. The overall control strategy used by patients appeared the same as that used by controls. Hand trajectories were approximately bell shaped, and movement extent was controlled by scaling a trajectory waveform in amplitude and time. However, both control subjects and patients showed systematic errors in movement extent that depended on the direction of hand movement. In control subjects, these systematic dependencies of extent on direction were small, but in patients they produced large and prominent errors. Analysis of the hand trajectories revealed that errors were associated with differences in velocity and acceleration for movements in different directions. In an earlier study, we showed that in subjects with normal sensation that the dependence of acceleration and velocity on direction results from a failure to take the inertial properties of the limb into account in programming the initial trajectory. In control subjects, these differences in initial acceleration are partially compensated by direction-dependent variations in movement time.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2002

Onset of chaotic dynamics in a ball mill: Attractors merging and crisis induced intermittency.

In mechanical treatment carried out by ball milling, powder particles are subjected to repeated high-energy mechanical loads which induce heavy plastic deformations together with fracturing and cold-welding events. Owing to the continuous defect accumulation and interface renewal, both structural and chemical transformations occur. The nature and the rate of such transformations have been shown to depend on variables, such as impact velocity and collision frequency that depend, in turn, on the whole dynamics of the system. The characterization of the ball dynamics under different impact conditions is then to be considered a necessary step in order to gain a satisfactory control of the experimental set up. In this paper we investigate the motion of a ball in a milling device. Since the ball motion is governed by impulsive forces acting during each collision, no analytical expression for the complete ball trajectory can be obtained. In addition, mechanical systems exhibiting impacts are strongly nonlinear due to sudden changes of velocities at the instant of impact. Many different types of periodic and chaotic impact motions exist indeed even for simple systems with external periodic excitation forces. We present results of the analysis on the ball trajectory, obtained from a suitable numerical model, under growing degree of impact elasticity. A route to high dimensional chaos is obtained. Crisis and attractors merging are also found. (c) 2002 American Institute of Physics.

Journal Article↗

PubMed2026

Single-cell analysis of the human retina reveals stage-linked microglial states and neural-immune circuit rewiring in diabetic retinopathy.

Diabetic retinopathy (DR) is a major cause of vision loss worldwide. Here, we conduct single-cell RNA sequencing of twenty human retina samples (from living and post-mortem donors) across non-diabetic, diabetic, and DR states to create a comprehensive transcriptomic atlas. We identify two stable microglial populations-homeostatic and inflammatory-that exist along a functional continuum, plus a neutrophil cluster within C1QA+ myeloid cells with dynamic transitions occurring throughout disease progression. Module-level analysis reveals divergent transcriptional trajectories: homeostatic microglia maintain energetic programs while selectively upregulating stress elements, whereas inflammatory microglia layer additional pro-inflammatory programs onto preserved biosynthetic foundations. Eleven co-expression modules organize into two major axes: an inflammatory-stress axis, and a regulatory/metabolic-motility axis, with a stable translation module persisting across disease stages. Cell communication analysis further highlights sophisticated neural-immune interactions, particularly between photoreceptors and microglia. Our findings provide insights into the complex cellular dynamics of DR progression and suggest potential therapeutic targets for early intervention.

Humans↗

PubMed1999

Vibrational population relaxation of carbon monoxide in the heme pocket of photolyzed carbonmonoxy myoglobin: comparison of time-resolved mid-IR absorbance experiments and molecular dynamics simulations.

The vibrational energy relaxation of carbon monoxide in the heme pocket of sperm whale myoglobin was studied by using molecular dynamics simulation and normal mode analysis methods. Molecular dynamics trajectories of solvated myoglobin were run at 300 K for both the delta- and epsilon-tautomers of the distal His-64. Vibrational population relaxation times of 335 +/- 115 ps for the delta-tautomer and 640 +/- 185 ps for the epsilon-tautomer were estimated by using the Landau-Teller model. Normal mode analysis was used to identify those protein residues that act as the primary "doorway" modes in the vibrational relaxation of the oscillator. Although the CO relaxation rates in both the epsilon- and delta-tautomers are similar in magnitude, the simulations predict that the vibrational relaxation of the CO is faster in the delta-tautomer with the distal His playing an important role in the energy relaxation mechanism. Time-resolved mid-IR absorbance measurements were performed on photolyzed carbonmonoxy hemoglobin (Hb(13)CO). From these measurements, a T(1) time of 600 +/- 150 ps was determined. The simulation and experimental estimates are compared and discussed.

Carbon Monoxide↗

PubMed2005

Folding time distributions as an approach to protein folding kinetics.

A 27-residue lattice heteropolymer subject to Monte Carlo dynamics on a simple cubic lattice is studied over a range of temperatures. Folding time distributions are used to obtain information concerning the details of folding kinetics. The results are compared with those from methods based on mean force surfaces expressed in terms of a reduced set of variables and on a disconnectivity graph for the same system. A detailed analysis of the folding trajectories is given, and the importance of dead-end traps in determining the folding time is demonstrated. We show that the calculated folding kinetics can be modeled by a system of kinetic equations, with the essential rate constants determined from the Monte Carlo simulations and the resulting folding time distributions. The kinetic equations make possible an analysis of the variation of the importance of different channels with temperature. In particular, we show that the presence of intermediates may be masked in the folding time distributions, with the mean folding time being independent of the height of the barrier between the intermediates and collapsed globule state of the system. This and other results demonstrate that care has to be used in interpreting experimental folding data in terms of the underlying kinetics. Correspondingly, simulations are shown to have to satisfy certain requirements to obtain proper sampling of the dead-end traps.

Kinetics↗

PubMed2000

A comparative analysis of the center of gravity and center of pressure trajectory path lengths in standing posture: an estimation of active stiffness.

The center of foot pressure (CP) motions, representing the net neuromuscular control, was compared to the center of gravity (CG) motions, representing the net performance. The comparison focused on the trajectory path length parameter along the medio-lateral and antero-posterior axes because these two variables depend on amplitude versus frequency relationship. This relationship was used to evaluate the CG motions based on the CP motions. Seven subjects stood still on a force plate with eyes open and eyes closed. The results showed that the ratio of (CP-CG)/CP trajectory path length was personal for each subject. These results suggest different levels of passive (ligaments, elastic properties) and active (reflex activity) stiffness. For some subjects, this ratio was significantly lower for the eyes open condition than for the eyes closed condition, indicating a decrease of the active stiffness for the eyes open condition. Therefore, a CG-CP comparative analysis appeared helpful in understanding the control of balance and necessary to quantify the subjects' net performance.

Adult↗

PubMed1998

Are there non-trivial dynamic cross-correlations in proteins?

The analysis of internal motion in ensembles of flexible molecules in coordinate space requires the removal of overall motion by a least-squares fitting procedure of the Cartesian coordinates. It has been demonstrated that the choice of the atom set used for fitting influences the picture of the internal motion of BPTI. We have performed essential dynamics analyses of a 1 ns molecular dynamics trajectory of the single-stranded DNA-binding protein from the Pf3 phage using either all alpha-carbon atoms or the least mobile ones for fitting the trajectory prior to the analysis. We found that covariances of atoms separated by long distances were significantly reduced in the latter case; the overall overlap of essential spaces was still high. In the second part we present a method that does not introduce and bias caused by overall motion: principal component analysis in distance space. Non-trivial dynamic cross-correlations were preserved in distance space, which answers the question posed in the title in the affirmative. However, cross-correlations were throughout smaller than those detected by standard essential dynamics analyses.

Bacteriophages↗

PubMed2002

Structure and properties of the dendron-encapsulated polyoxometalate (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], a first generation dendrizyme.

Combining analytical and theoretical methods, we present a detailed study of a heteropolytungstate cluster encapsulated in a shell of dendritically branching surfactants, namely (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], 3. This novel surfactant-encapsulated cluster (SEC) self-assembles spontaneously from polyoxometalate-containing solutions treated with a stoichiometric amount of dendrons. Compound 3 exhibits a discrete supramolecular architecture in which a single polyoxometalate anion resides in a compact shell of dendrons. Our approach attempts to combine the catalytic activity of polyoxometalates with the steric properties of tailored dendritic surfactants into size-selective catalytic systems. The structural characterization of the SEC is based on analytical ultracentrifugation (AUC) and small-angle neutron scattering (SANS). The packing arrangement of dendrons at the cluster surface is gleaned from molecular dynamics (MD) simulations, which suggests a highly porous shell structure due to the dynamic formation of internal clefts and cavities. From analysis of the MD trajectory of 3, a theoretical neutron-scattering function is derived that is in good agreement with experimental SANS data. Force field parameters used in MD simulations are partially derived from a quantum mechanical geometry optimization of [(Zn(H(2)O))(3)(SbW(9)O(33))(2)](12)(-), 2b, at the density functional theory (DFT) level. DFT calculations are corroborated by X-ray structure analysis of Na(6)K(6)[(Zn(H(2)O))(3)(SbW(9)O(33))(2)].23H(2)O, which is isostructural with the catalytically active Mn derivative 2a. The combined use of theoretical and analytical methods aims at rapidly prototyping smart catalysts ("dendrizymes"), which are structurally related to naturally occurring metalloproteins.

Journal Article↗

PubMed1983

Motor impairment after unilateral electrolytic lesions of the substantia nigra in baboons: behavioral data with quantitative and kinematic analysis of a pointing movement.

Unilateral electrolytic lesions of the substantia nigra (SN) were carried out stereotaxically on 4 baboons which had been previously trained to perform a visually guided pointing movement. For a few days after operation, all animals exhibited a behavioral impairment affecting the contralateral body half and consisting of dystonic flexed posture and akinesia. The animals were thus unable to perform the pointing task with the contralateral hand. After a delay which depended on the extent of the SN lesion, the animals began to make the pointing movement again. Postoperative changes were then observed only on the side opposite the SN lesion. These consisted of an increase in the latency and particularly the duration of the movement without any change in the accuracy. The kinematic analysis of the hand trajectory showed that the contralateral increase in the movement duration corresponded to a regular decrease in the velocities. Study of the recovery over 120 days after SN lesion showed a progressive improvement which was faster with regard to movement duration than to movement latency. These data clearly point to the functional role of the SN in the initiation and particularly in the execution of movement. Quantitative and kinematic analysis of this pointing movement makes it possible to detect and quantify very closely the changes in movement program and execution induced by a SN lesion. This experimental model will be useful for pharmacological in vivo studies allowing a more specific assessment of the functional role of the neurotransmitters involved in SN dysfunction.

Animals↗

PubMed1994

Multichannel evoked potentials as voltage space trajectories.

Multichannel brain evoked potentials can be represented as trajectories V(t) in n-dimensional voltage space, analogous to three-channel Lissajous trajectories (3-CLT). Equations of motion are developed based on an arbitrary number of dipole generators at arbitrary locations within the brain, and the properties of 3-CLT are generalized to the higher dimensional case. The trajectory is shown to be limited to k < n dimensions, and k channels are found to be sufficient for predicting the potential difference between any two points on the head, provided that an empirically determined set of linear functionals is known. A method for choosing the "best" m-channel montage (m < or = k) is described, by associating with each montage an alternating m-tensor on Rk. Planar analysis of the voltage trajectories is generalized to the k-dimensional case, in which m-planes are compared using a mapping between the Grassman manifold and real projective space.

Brain↗

PubMedDate not supplied

The k-trajectory formulation of the NMR imaging process with applications in analysis and synthesis of imaging methods.

The fundamental operations of nuclear magnetic resonance (NMR) imaging can be formulated, for a large number of methods, as sampling the object distribution in the Fourier spatial-frequency domain, followed by processing the digitized data (often simply by Fourier transformation) to produce a digital image. In these methods, which include reconstruction from projections, Fourier imaging, spin-warp imaging, and echo-planar imaging, controllable gradient fields determine the points in the spatial-frequency domain which are sampled at any given time during the acquisition of data (the free induction decay, or FID). The detailed time dependence of the resulting trajectory of sample points (the k trajectory) determines the relative weight and accuracy with which image information at each spatial frequency is measured, establishing theoretical limitations on image quality achievable with a given imaging method. We demonstrate here that these considerations may be used to compare the theoretical capabilities of NMR imaging methods, and to derive new imaging methods with optimal theoretical imaging properties.

Image Enhancement↗

PubMed1987

Trajectory control in targeted force impulses. III. Compensatory adjustments for initial errors.

In the preceding study (Gordon and Ghez 1987), we showed that accurately targeted isometric force impulses produced by human subjects are governed by a pulse height control policy. Different peak forces were achieved by modulating the rate of rise of force while force rise time was maintained close to a constant value and independent of peak force. An early measure of the rate of rise of force, peak d2F/dt2, was scaled to the required force (target amplitude) and highly predictive of the peak force achieved. In six subjects examined, peak d2F/dt2 accounted for between 70% and 96% of the total variance in peak force. In the present study, we further examined these targeted responses to determine whether the residual variability not predicted by peak d2F/dt2 could be accounted for by adjustments to the force trajectories which compensated for initial errors in the scaling of the d2F/dt2. A statistical model of the determinants of peak force was tested. This model included two paths by which the target amplitude could independently influence the peak force achieved. The first path was preprogrammed pulse height control. In this path, target amplitude determined the initial rate of rise of force (peak d2F/dt2) which in turn determined the final peak force achieved. The second path was an independent influence of errors in the initial scaling of peak d2F/dt2 on peak force. Multiple regression analysis was performed on trajectory variables within the sets of responses by each subject in each condition to determine whether the second path contributed significantly to explaining the variance in peak force. In each subject and condition, there was a significant independent influence of error in d2F/dt2 on peak force, and the direction of this effect was to decrease the magnitudes of peak force errors. These compensatory adjustments accounted for between 1% and 14% of the total variance in peak force. Further multiple regression analyses revealed that inappropriate scaling of the initial phase of the trajectories was compensated for by shortening or prolonging the force rise time. These trajectory adjustments were in turn implemented by modulation of the timing and magnitude of the contractions in the agonist and antagonist muscles that produced the force trajectories. Because these compensatory adjustments were evident in the EMG pattern at latencies too short to be accounted for by peripheral feedback, we assume that they depend on internal monitoring of the unfolding neural commands. These internal feedback processes act in parallel with the programmed commands, both determining the force trajectory.

Adaptation, Physiological↗

PubMed2004

Contact pair dynamics during folding of two small proteins: chicken villin head piece and the Alzheimer protein beta-amyloid.

The folding of an extended protein to its unique native state requires establishment of specific, predetermined, often distant, contacts between amino acid residue pairs. The dynamics of contact pair formation between various hydrophobic residues during folding of two different small proteins, the chicken villin head piece (HP-36) and the Alzheimer protein beta-amyloid (betaA-40), are investigated by Brownian dynamics (BD) simulations. These two proteins represent two very different classes-HP-36 being globular while betaA-40 is nonglobular, stringlike. Hydropathy scale and nonlocal helix propensity of amino acids are used to model the complex interaction potential among the various amino acid residues. The minimalistic model we use here employs a connected backbone chain of atoms of equal size while an amino acid is attached to each backbone atom as an additional atom of differing sizes and interaction parameters, determined by the characteristics of each amino acid. Even for such simple models, we find that the low-energy structures obtained by BD simulations of both the model proteins mimic the native state of the real protein rather well, with a best root-mean-square deviation of 4.5 A for HP-36. For betaA-40 (where a single well-defined structure is not available), the simulated structures resemble the reported ensemble rather well, with the well-known beta-bend correctly reproduced. We introduce and calculate a contact pair distance time correlation function, C(P) (ij)(t), to quantify the dynamical evolution of the pair contact formation between the amino acid residue pairs i and j. The contact pair time correlation function exhibits multistage dynamics, including a two stage fast collapse, followed by a slow (microsecond long) late stage dynamics for several specific pairs. The slow late stage dynamics is in accordance with the findings of Sali et al. Analysis of the individual trajectories shows that the slow decay is due to the attempt of the protein to form energetically more favorable pair contacts to replace the less favorable ones. This late stage contact formation is a highly cooperative process, involving participation of several pairs and thus entropically unfavorable and expected to face a large free energy barrier. This is because any new pair contact formation among hydrophobic pairs will require breaking of several contacts, before the favorable ones can be formed. This aspect of protein folding dynamics is similar to relaxation in glassy liquids, where also alpha relaxation requires highly cooperative process of hopping. The present analysis suggests that waiting time for the necessary pair contact formation may obey the Poissonian distribution. We also study the dynamics of Forster energy transfer during folding between two tagged amino acid pairs. This dynamics can be studied by fluorescence resonance energy transfer (FRET). It is found that suitably placed donor-acceptor pairs can capture the slow dynamics during folding. The dynamics probed by FRET is predicted to be nonexponential.

Alzheimer Disease↗

PubMed2002

Particle transport in a random velocity field with Lagrangian statistics.

The transport properties of a random velocity field with Kolmogorov spectrum and time correlations defined along Lagrangian trajectories are analyzed. The analysis is carried out in the limit of short correlation times, as a perturbation theory in the ratio, scale by scale, of the eddy decay and turnover time. Various quantities such as the Batchelor constant and the dimensionless constants entering the expression for particle relative and self-diffusion are given in terms of this ratio and of the Kolmogorov constant. Particular attention is paid to particles with finite inertia. The self-diffusion properties of a particle with Stokes time longer than the Kolmogorov time are determined, verifying on an analytical example the dimensional results of Olla [Phys. Fluids 14, 4266 (2002)]. Expressions for the fluid velocity Lagrangian correlations and correlation times along a solid particle trajectory are provided in several parameter regimes, including the infinite Stokes time limit corresponding to Eulerian correlations. The concentration fluctuation spectrum and the nonergodic properties of a suspension of heavy particles in a turbulent flow, in the same regime, are analyzed. The concentration spectrum is predicted to obey, above the scale of eddies with lifetime equal to the Stokes time, a power law with universal -4/3 exponent, and to be otherwise independent of the nature of the turbulent flow. A preference of the solid particle to lie in less energetic regions of the flow is observed.

Journal Article↗

PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans↗

PubMed1996

Cerebellar ataxia: abnormal control of interaction torques across multiple joints.

1. We studied seven subjects with cerebellar lesions and seven control subjects as they made reaching movements in the sagittal plane to a target directly in front of them. Reaches were made under three different conditions: 1) "slow-accurate," 2) "fast-accurate," and 3) "fast as possible." All subjects were videotaped moving in a sagittal plane with markers on the index finger, wrist, elbow, and shoulder. Marker positions were digitized and then used to calculate joint angles. For each of the shoulder, elbow and wrist joints, inverse dynamics equations based on a three-segment limb model were used to estimate the net torque (sum of components) and each of the component torques. The component torques consisted of the torque due to gravity, the dynamic interaction torques induced passively by the movement of the adjacent joint, and the torque produced by the muscles and passive tissue elements (sometimes called "residual" torque). 2. A kinematic analysis of the movement trajectory and the change in joint angles showed that the reaches of subjects with cerebellar lesions were abnormal compared with reaches of control subjects. In both the slow-accurate and fast-accurate conditions the cerebellar subjects made abnormally curved wrist paths; the curvature was greater in the slow-accurate condition. During the slow-accurate condition, cerebellar subjects showed target undershoot and tended to move one joint at a time (decomposition). During the fast-accurate reaches, the cerebellar subjects showed target overshoot. Additionally, in the fast-accurate condition, cerebellar subjects moved the joints at abnormal rates relative to one another, but the movements were less decomposed. Only three subjects were tested in the fast as possible condition; this condition was analyzed only to determine maximal reaching speeds of subjects with cerebellar lesions. Cerebellar subjects moved more slowly than controls in all three conditions. 3. A kinetic analysis of torques generated at each joint during the slow-accurate reaches and the fast-accurate reaches revealed that subjects with cerebellar lesions produced very different torque profiles compared with control subjects. In the slow-accurate condition, the cerebellar subjects produced abnormal elbow muscle torques that prevented the normal elbow extension early in the reach. In the fast-accurate condition, the cerebellar subjects produced inappropriate levels of shoulder muscle torque and also produced elbow muscle torques that did not very appropriately with the dynamic interaction torques that occurred at the elbow. Lack of appropriate muscle torque resulted in excessive contributions of the dynamic interaction torque during the fast-accurate reaches. 4. The inability to produce muscle torques that predict, accommodate, and compensate for the dynamic interaction torques appears to be an important cause of the classic kinematic deficits shown by cerebellar subjects during attempted reaching. These kinematic deficits include incoordination of the shoulder and the elbow joints, a curved trajectory, and overshoot. In the fast-accurate condition, cerebellar subjects often made inappropriate muscle torques relative to the dynamic interaction torques. Because of this, interaction torques often determined the pattern of incoordination of the elbow and shoulder that produced the curved trajectory and target overshoot. In the slow-accurate condition, we reason that the cerebellar subjects may use a decomposition strategy so as to simplify the movement and not have to control both joints simultaneously. From these results, we suggest that a major role of the cerebellum is in generating muscle torques at a joint that will predict the interaction torques being generated by other moving joints and compensate for them as they occur.

Adult↗

PubMed2001

Direct measurements of multiple adhesive alignments and unbinding trajectories between cadherin extracellular domains.

Direct measurements of the interactions between antiparallel, oriented monolayers of the complete extracellular region of C-cadherin demonstrate that, rather than binding in a single unique orientation, the cadherins adhere in three distinct alignments. The strongest adhesion is observed when the opposing extracellular fragments are completely interdigitated. A second adhesive alignment forms when the interdigitated proteins separate by 70 +/- 10 A. A third complex forms at a bilayer separation commensurate with the approximate overlap of cadherin extracellular domains 1 and 2 (CEC1-2). The locations of the energy minima are independent of both the surface density of bound cadherin and the stiffness of the force transducer. Using surface element integration, we show that two flat surfaces that interact through an oscillatory potential will exhibit discrete minima at the same locations in the force profile measured between hemicylinders covered with identical materials. The measured interaction profiles, therefore, reflect the relative separations at which the antiparallel proteins adhere, and are unaffected by the curvature of the underlying substrate. The successive formation and rupture of multiple protein contacts during detachment can explain the observed sluggish unbinding of cadherin monolayers. Velocity-distance profiles, obtained by quantitative video analysis of the unbinding trajectory, exhibit three velocity regimes, the transitions between which coincide with the positions of the adhesive minima. These findings suggest that cadherins undergo multiple stage unbinding, which may function to impede adhesive failure under force.

Animals↗

PubMed1987

Hyperactivated motility induced in mouse sperm by calcium ionophore A23187 is reversible.

The reversibility of hyperactivated motility was tested in caudal epididymal mouse sperm by treating them with 1 microM calcium ionophore A23187 in dimethyl sulfoxide (DMSO), followed 2 min later by the addition of medium containing high levels of bovine serum albumin (BSA) (final concentrations: 0.5 microM A23187, 22 mg/ml BSA). Controls received DMSO alone, followed by BSA. Immediately following treatment with A23187, motility was weak and vibratory. Two minutes after the addition of high levels of BSA, motility was hyperactivated, as determined by videotape analysis of linearity of trajectory and acuteness of flagellar bending. Ten minutes after the addition, the movement pattern returned to that of fresh, uncapacitated epididymal sperm. Control sperm retained the linear swimming pattern of fresh caudal epididymal sperm during the 10 min of observation. Ninety minutes later, however, both control and treated sperm became hyperactivated. The percentage of motile sperm was not affected by treatment or time. Thus, ionophore-induced hyperactivation is reversible and does not interfere with the normal development of hyperactivation during incubation under capacitating conditions in vitro.

Analysis of Variance↗