The forward rate of binding of surface-tethered reactants: effect of relative motion between two surfaces.
The reaction of molecules confined to two dimensions is of interest in cell adhesion, specifically for the reaction between cell surface receptors and substrate-bound ligand. We have developed a model to describe the overall rate of reaction of species that are bound to surfaces under relative motion, such that the Peclet number is order one or greater. The encounter rate between reactive species is calculated from solution of the two-dimensional convection-diffusion equation. The probability that each encounter will lead to binding depends on the intrinsic rate of reaction and the encounter duration. The encounter duration is obtained from the theory of first passage times. We find that the binding rate increases with relative velocity between the two surfaces, then reaches a plateau. This plateau indicates that the increase in the encounter rate is counterbalanced by the decrease in the encounter duration as the relative velocity increases. The binding rate is fully described by two dimensionless parameters, the Peclet number and the Damkohler number. We use this model to explain data from the cell adhesion literature by incorporating these rate laws into "adhesive dynamics" simulations to model the binding of a cell to a surface under flow. Leukocytes are known to display a "shear threshold effect" when binding selectin-coated surfaces under shear flow, defined as an increase in bind rate with shear; this effect, as calculated here, is due to an increase in collisions between receptor and ligand with increasing shear. The model can be used to explain other published data on the effect of wall shear rate on the binding of cells to surfaces, specifically the mild decrease in binding within a fixed area with increasing shear rate. (+info)
Synchronization of local neural networks in the somatosensory cortex: A comparison of stationary and moving stimuli.
Spontaneous and stimulus-induced responses were recorded from neighboring groups of neurons by an array of electrodes in the primary (SI) somatosensory cortex of intact, halothane-anesthetized cats. Cross-correlation analysis was used to characterize the coordination of spontaneous activity and the responses to peripheral stimulation with moving or stationary air jets. Although synchronization was detected in only 10% (88 of 880) of the pairs of single neurons that were recorded, cross-correlation analysis of multiunit responses revealed significant levels of synchronization in 64% of the 123 recorded electrode pairs. Compared with spontaneous activity, both stationary and moving air jets caused substantial increases in the rate, proportion, and temporal precision of synchronized activity in local regions of SI cortex. Among populations of neurons that were synchronized by both types of air-jet stimulation, the mean rate of synchronized activity was significantly higher during moving air-jet stimulation than during stationary air-jet stimulation. Moving air jets also produced significantly higher correlation coefficients than stationary air jets in the raw cross-correlograms (CCGs) but not in the shift-corrected CCGs. The incidence and rate of stimulus-induced synchronization varied with the distance separating the recording sites. For sites separated by /=500 microm, only 37% of the multiunit responses were synchronized by discrete stimulation with a single air jet. Measurements of the multiunit CCG peak half-widths showed that the correlated activity produced by moving air jets had slightly less temporal variability than that produced by stationary air jets. These results indicate that moving stimuli produce greater levels of synchronization than stationary stimuli among local groups of SI neurons and suggest that neuronal synchronization may supplement the changes in firing rate which code intensity and other attributes of a cutaneous stimulus. (+info)
DNA translocation blockage, a general mechanism of cleavage site selection by type I restriction enzymes.
Type I restriction enzymes bind to a specific DNA sequence and subsequently translocate DNA past the complex to reach a non-specific cleavage site. We have examined several potential blocks to DNA translocation, such as positive supercoiling or a Holliday junction, for their ability to trigger DNA cleavage by type I restriction enzymes. Introduction of positive supercoiling into plasmid DNA did not have a significant effect on the rate of DNA cleavage by EcoAI endonuclease nor on the enzyme's ability to select cleavage sites randomly throughout the DNA molecule. Thus, positive supercoiling does not prevent DNA translocation. EcoR124II endonuclease cleaved DNA at Holliday junctions present on both linear and negatively supercoiled substrates. The latter substrate was cleaved by a single enzyme molecule at two sites, one on either side of the junction, consistent with a bi-directional translocation model. Linear DNA molecules with two recognition sites for endonucleases from different type I families were cut between the sites when both enzymes were added simultaneously but not when a single enzyme was added. We propose that type I restriction enzymes can track along a DNA substrate irrespective of its topology and cleave DNA at any barrier that is able to halt the translocation process. (+info)
Sensitivity to simulated directional sound motion in the rat primary auditory cortex.
Sensitivity to simulated directional sound motion in the rat primary auditory cortex. This paper examines neuron responses in rat primary auditory cortex (AI) during sound stimulation of the two ears designed to simulate sound motion in the horizontal plane. The simulated sound motion was synthesized from mathematical equations that generated dynamic changes in interaural phase, intensity, and Doppler shifts at the two ears. The simulated sounds were based on moving sources in the right frontal horizontal quadrant. Stimuli consisted of three circumferential segments between 0 and 30 degrees, 30 and 60 degrees, and 60 and 90 degrees and four radial segments at 0, 30, 60, and 90 degrees. The constant velocity portion of each segment was 0.84 m long. The circumferential segments and center of the radial segments were calculated to simulate a distance of 2 m from the head. Each segment had two trajectories that simulated motion in both directions, and each trajectory was presented at two velocities. Young adult rats were anesthetized, the left primary auditory cortex was exposed, and microelectrode recordings were obtained from sound responsive cells in AI. All testing took place at a tonal frequency that most closely approximated the best frequency of the unit at a level 20 dB above the tuning curve threshold. The results were presented on polar plots that emphasized the two directions of simulated motion for each segment rather than the location of sound in space. The trajectory exhibiting a "maximum motion response" could be identified from these plots. "Neuron discharge profiles" within these trajectories were used to demonstrate neuron activity for the two motion directions. Cells were identified that clearly responded to simulated uni- or multidirectional sound motion (39%), that were sensitive to sound location only (19%), or that were sound driven but insensitive to our location or sound motion stimuli (42%). The results demonstrated the capacity of neurons in rat auditory cortex to selectively process dynamic stimulus conditions representing simulated motion on the horizontal plane. Our data further show that some cells were responsive to location along the horizontal plane but not sensitive to motion. Cells sensitive to motion, however, also responded best to the moving sound at a particular location within the trajectory. It would seem that the mechanisms underlying sensitivity to sound location as well as direction of motion converge on the same cell. (+info)
Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations.
Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations. The effect of vertical eye-in-head position on the compensatory eye rotation response to passive and active high acceleration yaw head rotations was examined in eight normal human subjects. The stimuli consisted of brief, low amplitude (15-25 degrees ), high acceleration (4,000-6,000 degrees /s2) yaw head rotations with respect to the trunk (peak velocity was 150-350 degrees /s). Eye and head rotations were recorded in three-dimensional space using the magnetic search coil technique. The input-output kinematics of the three-dimensional vestibuloocular reflex (VOR) were assessed by finding the difference between the inverted eye velocity vector and the head velocity vector (both referenced to a head-fixed coordinate system) as a time series. During passive head impulses, the head and eye velocity axes aligned well with each other for the first 47 ms after the onset of the stimulus, regardless of vertical eye-in-head position. After the initial 47-ms period, the degree of alignment of the eye and head velocity axes was modulated by vertical eye-in-head position. When fixation was on a target 20 degrees up, the eye and head velocity axes remained well aligned with each other. However, when fixation was on targets at 0 and 20 degrees down, the eye velocity axis tilted forward relative to the head velocity axis. During active head impulses, the axis tilt became apparent within 5 ms of the onset of the stimulus. When fixation was on a target at 0 degrees, the velocity axes remained well aligned with each other. When fixation was on a target 20 degrees up, the eye velocity axis tilted backward, when fixation was on a target 20 degrees down, the eye velocity axis tilted forward. The findings show that the VOR compensates very well for head motion in the early part of the response to unpredictable high acceleration stimuli-the eye position- dependence of the VOR does not become apparent until 47 ms after the onset of the stimulus. In contrast, the response to active high acceleration stimuli shows eye position-dependence from within 5 ms of the onset of the stimulus. A model using a VOR-Listing's law compromise strategy did not accurately predict the patterns observed in the data, raising questions about how the eye position-dependence of the VOR is generated. We suggest, in view of recent findings, that the phenomenon could arise due to the effects of fibromuscular pulleys on the functional pulling directions of the rectus muscles. (+info)
Lumbar intradiscal pressure after posterolateral fusion and pedicle screw fixation.
In vitro biomechanical testing was performed in single-functional spinal units of fresh calf lumbar spines, using pressure needle transducers to investigate the effect of posterolateral fusion (PLF) and pedicle screw constructs (PS) on intradiscal pressure (IDP), in order to elucidate the mechanical factors concerned with residual low back pain after PLF. IDP of 6 calf lumbar spines consisting of L4 and L5 vertebrae and an intervening disc was measured under axial compression, flexion-extension and lateral bending in the intact spine, PS, PLF and the destabilized spine. Relative to the intact spines, the destabilized spines showed increased IDP in all of lordings and moments. IDP under PS and PLF were significantly decreased in axial compression, extension and lateral bending loads (p<0.05). In flexion, IDP under PS and PLF increased linearly proportional to the magnitude of flexion moment and reached as high as IDP of the intact spines. These results demonstrated that despite an increase in the stiffness of motion segments after PLF and PS, significant high disc pressure is still generated in flexion. Flexibility of PS and PLF may cause increased axial load sharing of the disc in flexion and increased IDP. This high IDP may explain patients' persisting pain following PS and PLF. (+info)
Electromyographic study of the elbow flexors and extensors in a motion of forearm pronation/supination while maintaining elbow flexion in humans.
Activities of the elbow flexors (biceps brachii, BB; brachialis, B; brachioradialis, BR) and extensors (triceps brachii, TB) in a motion of forearm pronation/supination with maintenance of elbow flexion (PS-movement) in nine healthy human subjects were studied by electromyography (EMG). The subject performed the PS-movement slowly or quickly with or without a load extending the elbow. In the slow PS-movement, an increase and decrease of EMG activities during supination and pronation, respectively, were seen in BB and the reverse was in B. A clear increment of EMG activities in BB accompanied with a reduction of EMG activities in B and/or BR, and the reverse were often observed. The contraction level and gain with the forearm supine were higher and larger than those with the forearm prone, respectively, in BB and the reverse was in B and BR. In a series of the quick PS-movement, alternating increases of EMG activities between BB and the other flexors (B and BR) were seen. Since TB showed no EMG activities throughout the experiment, it is suggested that reciprocal contractions between BB and the other flexors, which produce a complementary force in flexion direction, enable motions of pronation/supination with maintenance of flexion. Contraction properties of the flexors were discussed. (+info)
Direct measurement of inter-doublet elasticity in flagellar axonemes.
The outer doublet microtubules in ciliary and flagellar axonemes are presumed to be connected with each other by elastic links called the inter-doublet links or the nexin links, but it is not known whether there actually are such elastic links. In this study, to detect the elasticity of the putative inter-doublet links, shear force was applied to Chlamydomonas axonemes with a fine glass needle and the longitudinal elasticity was determined from the deflection of the needle. Wild-type axonemes underwent a high-frequency, nanometer-scale vibration in the presence of ATP. When longitudinal shear force was applied, the average position of the needle tip attached to the axoneme moved linearly with the force applied, yielding an estimate of spring constant of 2.0 (S.D.: 0.8) pN/nm for 1 microm of axoneme. This value did not change in the presence of vanadate, i.e., when dynein does not form strong cross bridges. In contrast, it was at least five times larger when ATP was absent, i.e., when dynein forms strong cross bridges. The measured elasticity did not significantly differ in various mutant axonemes lacking the central-pair microtubules, a subset of inner-arm dynein, outer-arm dynein, or the radial spokes, although it was somewhat smaller in the latter two mutants. It was also observed that the shear displacement in an axoneme in the presence of ATP often took place in a stepwise manner. This suggests that the inter-doublet links can reversibly detach from and reattach to the outer doublets in a cooperative manner. This study thus provides the first direct measure of the elasticity of inter-doublet links and also demonstrates its dynamic nature. (+info)