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PubMed2004

Colpocystoproctography in the upright and supine positions correlated with dynamic MRI of the pelvic floor.

PURPOSE: To test whether there are statistically significant differences between measurement results on colpocystoproctography in the upright and the supine positions, and to correlate these results with dynamic MRI. PATIENTS AND METHODS: Seven patients with pelvic floor descent had received colpocystoproctography in the upright and supine positions and, additionally, dynamic MRI of the pelvic floor. Bladder neck position, angle of urethral inclination, posterior vesicourethral angle, and vaginal vault position were measured at relaxed pelvic floor and at pelvic strain. Differences between the measurement results of each parameter in the upright and supine position on colpocystoproctography were calculated and correlated with the measurement results from the dynamic MRI. RESULTS: At pelvic strain, bladder neck position, angle of urethral inclination, posterior vesicourethral angle and vaginal vault position measurements showed no statistically significant differences between colpocystoproctography in the upright and supine positions or dynamic MRI. For the bladder neck height at pelvic floor relaxation, significant differences were found between colpocystoproctography in the upright and supine positions, and colpocystoproctography in the upright position versus dynamic MRI. CONCLUSION: At pelvic strain, measurement data from dynamic MRI are not statistically different from data from colpocystoproctography either in supine and upright positions.

Aged↗
PubMed2001

The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I.

Articular cartilage is routinely subjected to mechanical forces and to cell-regulatory molecules. Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal, dynamic compression and insulin-like growth factor-I (IGF-I), a polypeptide in synovial fluid that is anabolic for cartilage. In bovine patellofemoral cartilage explants, IGF-I increased protein and proteoglycan synthesis 90% and 120%, respectively while dynamic compression increased protein and proteoglycan synthesis 40% and 90%, respectively. Stimulation by IGF-I was significantly greater than by dynamic compression for both protein and proteoglycan synthesis. When applied together, the two stimuli enhanced protein and proteoglycan synthesis by 180% and 290%, respectively, a degree greater than that achieved by either stimulus alone. IGF-I augmented protein synthesis with a time constant of 12.2 h. Dynamic compression increased protein synthesis with a time constant of 2.9 h, a rate significantly faster than that of IGF-I, suggesting that these signals act via distinct cell activation pathways. When used together, dynamic compression and IGF-I acted with a time constant of 5.6 h. Thus, dynamic compression accelerated the biosynthetic response to IGF-I and increased transport of IGF-I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells.

Animals↗
PubMed1997

Dose to the contralateral breast: a comparison of two techniques using the enhanced dynamic wedge versus a standard wedge.

The dose to the contralateral breast has been associated with an increased risk of developing a second breast malignancy. Varying techniques have been devised and described in the literature to minimize this dose. Metal beam modifiers such as standard wedges are used to improve the dose distribution in the treated breast, but unfortunately introduce an increased scatter dose outside the treatment field, in particular to the contralateral breast. The enhanced dynamic wedge is a means of remote wedging created by independently moving one collimator jaw through the treatment field during dose delivery. This study is an analysis of differing doses to the contralateral breast using two common clinical set-up techniques with the enhanced dynamic wedge versus the standard metal wedge. A tissue equivalent block (solid water), modeled to represent a typical breast outline, was designed as an insert in a Rando phantom to simulate a standard patient being treated for breast conservation. Tissue equivalent material was then used to complete the natural contour of the breast and to reproduce appropriate build-up and internal scatter. Thermoluminescent dosimeter (TLD) rods were placed at predetermined distances from the geometric beam's edge to measure the dose to the contralateral breast. A total of 35 locations were used with five TLDs in each location to verify the accuracy of the measured dose. The radiation techniques used were an isocentric set-up with co-planar, non divergent posterior borders and an isocentric set-up with a half beam block technique utilizing the asymmetric collimator jaw. Each technique used compensating wedges to optimize the dose distribution. A comparison of the dose to the contralateral breast was then made with the enhanced dynamic wedge vs. the standard metal wedge. The measurements revealed a significant reduction in the contralateral breast dose with the enhanced dynamic wedge compared to the standard metal wedge in both set-up techniques. The dose was measured at varying distances from the geometric field edge, ranging from 2 to 8 cm. The average dose with the enhanced dynamic wedge was 2.7-2.8%. The average dose with the standard wedge was 4.0-4.7%. Thermoluminescent dosimeter measurements suggest an increase in both scattered electrons and photons with metal wedges. The enhanced dynamic wedge is a practical clinical advance which improves the dose distribution in patients undergoing breast conservation while at the same time minimizing dose to the contralateral breast, thereby reducing the potential carcinogenic effects.

Breast↗
PubMed1997

Treatment planning for enhanced dynamic wedge with the CMS focus/Modulex treatment planning system.

The current versions of the CMS treatment planning systems, the FOCUS system for three dimensional planning, and Modulex for two dimensional planning, both require modeling dynamic wedges as filters. In this paper we describe methods for generating dynamic wedge filters for treatment planning. In our previous work with dynamic wedge we used measured data to back project the filter that would have delivered the wedge shaped isodoses. With the current version of Enhanced Dynamic Wedge, we use the segmented treatment table (STT) to create filters. For each wedge angle we created a 30 cm filter, for which the field is truncated by blocks according to the dynamic jaw settings. We found the filters provided isodoses that were within 2 degrees of the measured angles. Central axis dose was within 1% due to the fact the system does not account for beam hardening. Although an undesirable solution to model dynamic wedging, we found the filter method to be workable.

Radiotherapy Planning, Computer-Assisted↗
PubMed2001

The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics.

Cytoplasmic dynein is a multisubunit, minus end-directed microtubule motor that uses dynactin as an accessory complex to perform various in vivo functions including vesicle transport, spindle assembly, and nuclear distribution [1]. We previously showed that in the filamentous fungus Aspergillus nidulans, a GFP-tagged cytoplasmic dynein heavy chain (NUDA) forms comet-like structures that exhibited microtubule-dependent movement toward and back from the hyphal tip [2]. Here we demonstrate that another protein in the NUDA pathway, NUDF, which is homologous to the human LIS1 protein involved in brain development [3, 4], also exhibits such dynamic behavior. Both NUDA and NUDF are located at the ends of microtubules, and this observation suggests that the observed dynamic behavior is due to their association with the dynamic microtubule ends. To address whether NUDA and NUDF play a role in regulating microtubule dynamics in vivo, we constructed a GFP-labeled alpha-tubulin strain and used it to compare microtubule dynamics in vivo in wild-type A. nidulans versus temperature-sensitive loss-of-function mutants of nudA and nudF. The mutants showed a lower frequency of microtubule catastrophe, a lower rate of shrinkage during catastrophe, and a lower frequency of rescue. The microtubules in the mutant cells also paused longer at the hyphal tip than wild-type microtubules. These results indicate that cytoplasmic dynein and the LIS1 homolog NUDF affect microtubule dynamics in vivo.

Aspergillus nidulans↗
PubMed2002

Biomechanics and muscle coordination of human walking. Part I: introduction to concepts, power transfer, dynamics and simulations.

Current understanding of how muscles coordinate walking in humans is derived from analyses of body motion, ground reaction force and EMG measurements. This is Part I of a two-part review that emphasizes how muscle-driven dynamics-based simulations assist in the understanding of individual muscle function in walking, especially the causal relationships between muscle force generation and walking kinematics and kinetics. Part I reviews the strengths and limitations of Newton-Euler inverse dynamics and dynamical simulations, including the ability of each to find the contributions of individual muscles to the acceleration/deceleration of the body segments. We caution against using the concept of biarticular muscles transferring power from one joint to another to infer muscle coordination principles because energy flow among segments, even the adjacent segments associated with the joints, cannot be inferred from computation of joint powers and segmental angular velocities alone. Rather, we encourage the use of dynamical simulations to perform muscle-induced segmental acceleration and power analyses. Such analyses have shown that the exchange of segmental energy caused by the forces or accelerations induced by a muscle can be fundamentally invariant to whether the muscle is shortening, lengthening, or neither. How simulation analyses lead to understanding the coordination of seated pedaling, rather than walking, is discussed in this first part because the dynamics of pedaling are much simpler, allowing important concepts to be revealed. We elucidate how energy produced by muscles is delivered to the crank through the synergistic action of other non-energy producing muscles; specifically, that a major function performed by a muscle arises from the instantaneous segmental accelerations and redistribution of segmental energy throughout the body caused by its force generation. Part II reviews how dynamical simulations provide insight into muscle coordination of walking.

Bicycling↗
PubMed2003

Cerebral blood flow and dynamic cerebral autoregulation during ethanol intoxication and hypercapnia.

More than one-third of patients diagnosed with head injury are intoxicated with ethanol. Most clinical and animal studies have shown alcohol to have a deleterious impact in the setting of cerebrovascular trauma; however, there are also data showing neuroprotective effects in low ethanol doses. Human studies using imaging modalities suggest that small doses of alcohol produce cerebral vasodilatation and higher doses cerebral vasoconstriction. The aim of this study was to investigate the effect of ethanol intake on dynamic cerebral autoregulation and velocities in the middle cerebral arteries, and compare these changes with the effects of hypercapnia. Dynamic cerebral autoregulation and cerebral blood flow velocities were analysed before and after alcohol intake (1.1 g/kg of body weight) in six adult volunteers. Cerebral blood flow velocities in both middle cerebral arteries were monitored continuously by transcranial Doppler. A value for dynamic cerebral autoregulation was calculated from the rate of increase in middle cerebral artery velocities after a rapid-step decrease in arterial blood pressure. A sudden decrease in blood pressure was achieved by the release of previously inflated large blood pressure cuffs around the subject's thighs. Three volunteers were also tested before alcohol intake with CO(2) challenge (breathing 6% CO(2)) during the autoregulation procedure. Blood alcohol level reached 90 mg/dl approximately 60 min after ethanol ingestion. Cerebral blood velocities increased by 8% from baseline for uncorrected end-tidal (et) CO(2) and by 24% for correction to et CO(2)=40. Dynamic cerebral autoregulation measured as an autoregulation index decreased from 4.3+/-1.3 to 2.9+/-1.1 (p=0.089), which did not reach statistical significance. During hypercapnic conditions, dynamic cerebral autoregulation dropped from 4+/-0.8 to 0.9+/-0.9. In conclusion, mild alcohol intoxication caused cerebral vasodilatation with a subsequent increase in cerebral blood flow of 8-24%. Dynamic cerebral autoregulation was not found to be significantly impaired by ethanol. Hypercapnia almost completely destroys the physiological autoregulatory mechanism. A mild hyper-ventilation to etCO(2)=34-36 may be a compensatory contra-measure for ethanol-induced vasodilatation in the setting of head trauma.

Adult↗
PubMed2003

An estimation of the influence of force decrease on the mean power spectral frequency shift of the EMG during repetitive maximum dynamic knee extensions.

Frequency analysis of myoelectric (ME) signals, using the mean power spectral frequency (MNF), has been widely used to characterize peripheral muscle fatigue during isometric contractions assuming constant force. However, during repetitive isokinetic contractions performed with maximum effort, output (force or torque) will decrease markedly during the initial 40-60 contractions, followed by a phase with little or no change. MNF shows a similar pattern. In situations where there exist a significant relationship between MNF and output, part of the decrease in MNF may per se be related to the decrease in force during dynamic contractions. This study estimated force effects on the MNF shifts during repetitive dynamic knee extensions. Twenty healthy volunteers participated in the study and both surface ME signals (from the right vastus lateralis, vastus medialis, and rectus femoris muscles) and the biomechanical signals (force, position, and velocity) of an isokinetic dynamometer were measured. Two tests were performed: (i) 100 repetitive maximum isokinetic contractions of the right knee extensors, and (ii) five gradually increasing static knee extensions before and after (i). The corresponding ME signal time-frequency representations were calculated using the continuous wavelet transform. Compensation of the MNF variables of the repetitive contractions was performed with respect to the individual MNF-force relation based on an average of five gradually increasing contractions. Whether or not compensation was necessary was based on the shape of the MNF-force relationship. A significant compensation of the MNF was found for the repetitive isokinetic contractions. In conclusion, when investigating maximum dynamic contractions, decreases in MNF can be due to mechanisms similar to those found during sustained static contractions (force-independent component of fatigue) and in some subjects due to a direct effect of the change in force (force-dependent component of fatigue). In order to compare MNF shifts during sustained static and repetitive dynamic contractions it is necessary to estimate the force-dependent component of fatigue of dynamic contractions. Our results are preliminary and have to be confirmed in larger experiments using single dynamic contractions when determining the MNF-force relationship of the unfatigued situation.

Adolescent↗
PubMed2003

Dynamic interaction between a fingerpad and a flat surface: experiments and analysis.

Many neural and vascular diseases in hands and fingers have been related to the degenerative responses of local neural and vascular systems in fingers to excessive dynamic loading. Since fingerpads serve as a coupling element between the hand and the objects, the investigation of the dynamic coupling between fingertip and subjects could provide important information for the understanding of the pathomechanics of these neural and vascular diseases. In the present study, the nonlinear and time-dependent force responses of fingertips during dynamic contact have been investigated experimentally and theoretically. Four subjects (2 male and 2 female) with an average age of 24 years participated in the study. The index fingers of right and left hands of each subject were compressed using a flat platen via a micro testing machine. A physical model was proposed to simulate the nonlinear and time-dependent force responses of fingertips during dynamic contact. Using a force relaxation test and a fast loading test at constant loading speed, the material/structural parameters underlying the proposed physical model could be identified. The predicted rate-dependent force/displacement curves and time-histories of force responses of fingertips were compared with those measured in the corresponding experiments. Our results suggest that the force responses of fingertips during the dynamic contacts are nonlinear and time-dependent. The physical model was verified to characterize the nonlinear, rate-dependent force-displacement behaviors, force relaxations, and time-histories of force responses of fingertips during dynamic contact.

Adult↗
PubMed2001

Modulation of appositional and longitudinal bone growth in the rat ulna by applied static and dynamic force.

Appositional and longitudinal growth of long bones are influenced by mechanical stimuli. Using the noninvasive rat ulna loading model, we tested the hypothesis that brief-duration (10 min/day) static loads have an inhibitory effect on appositional bone formation in the middiaphysis of growing rat ulnae. Several reports have shown that ulnar loading, when applied to growing rats, results in suppressed longitudinal growth. We tested a second hypothesis that load-induced longitudinal growth suppression in the growing rat ulna is proportional to time-averaged load, and that growth plate dimensions and chondrocyte populations are reduced in the loaded limbs. Growing male rats were divided into one of three groups receiving daily 10 min bouts of static loading at 17 N, static loading at 8.5 N, or dynamic loading at 17 N. Periosteal bone formation rates, measured 3 mm distal to the ulnar midshaft, were suppressed significantly (by 28-41%) by the brief static loading sessions despite normal (dynamic) limb use between the daily loading bouts. Static loading neither suppressed nor enhanced endocortical bone formation. Dynamic loading increased osteogenesis significantly on both surfaces. At the end of the 2 week loading experiment, loaded ulnae were approximately 4% shorter than the contralateral controls in the 17 N static and dynamic groups, and approximately 2% shorter than the control side in the 8.5 N static group, suggesting that growth suppression was proportional to peak load magnitude, regardless of whether the load was static or dynamic. The suppressed growth in loaded limbs was associated with thicker distal growth plates, particularly in the hypertrophic zone, and a concurrent retention of hypertrophic cell lacunae. Negligible effects were observed in the proximal growth plate. The results demonstrate that, in growing animals, even short periods of static loading can significantly suppress appositional growth; that dynamic loads trigger the adaptive response in bone; and that longitudinal growth suppression resulting from compressive end-loads is proportional to load magnitude and not average load.

Animals↗
PubMed2000

Toward a quantitative description of large-scale neocortical dynamic function and EEG.

A general conceptual framework for large-scale neocortical dynamics based on data from many laboratories is applied to a variety of experimental designs, spatial scales, and brain states. Partly distinct, but interacting local processes (e.g., neural networks) arise from functional segregation. Global processes arise from functional integration and can facilitate (top down) synchronous activity in remote cell groups that function simultaneously at several different spatial scales. Simultaneous local processes may help drive (bottom up) macroscopic global dynamics observed with electroencephalography (EEG) or magnetoencephalography (MEG). A local/global dynamic theory that is consistent with EEG data and the proposed conceptual framework is outlined. This theory is neutral about properties of neural networks embedded in macroscopic fields, but its global component makes several qualitative and semiquantitative predictions about EEG measures of traveling and standing wave phenomena. A more general "metatheory" suggests what large-scale quantitative theories of neocortical dynamics may be like when more accurate treatment of local and nonlinear effects is achieved. The theory describes the dynamics of excitatory and inhibitory synaptic action fields. EEG and MEG provide large-scale estimates of modulation of these synaptic fields around background levels. Brain states are determined by neuromodulatory control parameters. Purely local states are dominated by local feedback gains and rise and decay times of postsynaptic potentials. Dominant local frequencies vary with brain region. Other states are purely global, with moderate to high coherence over large distances. Multiple global mode frequencies arise from a combination of delays in corticocortical axons and neocortical boundary conditions. Global frequencies are identical in all cortical regions, but most states involve dynamic interactions between local networks and the global system. EEG frequencies may involve a "matching" of local resonant frequencies with one or more of the many, closely spaced global frequencies.

Cerebral Cortex↗
PubMed1998

The dynamical hypothesis in cognitive science.

According to the dominant computational approach in cognitive science, cognitive agents are digital computers; according to the alternative approach, they are dynamical systems. This target article attempts to articulate and support the dynamical hypothesis. The dynamical hypothesis has two major components: the nature hypothesis (cognitive agents are dynamical systems) and the knowledge hypothesis (cognitive agents can be understood dynamically). A wide range of objections to this hypothesis can be rebutted. The conclusion is that cognitive systems may well be dynamical systems, and only sustained empirical research in cognitive science will determine the extent to which that is true.

Cognition↗
PubMed2004

Trajectories of dynamic predictors of disorder: their meanings and implications.

Developmental psychopathologists are increasingly focused on characterizing heterogeneity of trajectories of psychological disorders across the life course (e.g., developmentally limited vs. chronic forms of disorder). Although the developmental significance of trajectories has been highlighted, there has been little attention to relations between trajectories and their etiologically and clinically relevant time-varying covariates (dynamic predictors). Depending upon the functional relation between a disorder and a dynamic predictor, we expect to see different trajectories of dynamic predictors. Thus, we propose a taxonomy of trajectories of dynamic predictors of course of disorder and provide an initial investigation into its validity. Using a mixed-gender, high-risk sample of young adults followed over 7 years, we identified dynamic predictors that covary with the course of alcohol use disorder (AUD). Based on a logically derived classification to facilitate interpretation of findings, three comparison groups were examined: persons whose AUD "remitted" (n = 33), those with a chronic AUD (n = 29), and nondiagnosers (n = 274). We hypothesized seven patterns of dynamic prediction (stable vulnerability indicators, course trackers, deterioration markers, developmentally specific variables, developmental lag markers, course-referenced variables, and recovery behaviors) and found evidence for five of them. The interpretation of markers of risk for development and course of AUDs and their implications for prevention, early intervention and formal/self-change treatments are discussed.

Adult↗
PubMed1995

Kinetic stabilization of microtubule dynamics at steady state in vitro by substoichiometric concentrations of tubulin-colchicine complex.

We have analyzed the effects of tubulin-colchicine (TC)-complex on the dynamic instability behavior of bovine brain microtubules at steady state in vitro using video microscopy. Incorporation of low numbers of TC-complexes per microtubule strongly suppressed dynamics at the plus ends by reducing the rate and extent of growing and shortening and by increasing the time microtubules spent in an attenuated state, neither growing nor shortening detectably. In addition, TC-complex strongly suppressed the catastrophe frequency and increased the rescue frequency. At low concentrations (0.02-0.05 microM), TC-complex suppressed dynamics without reducing the polymer mass or the mean microtubule length. Such strong suppression of microtubule dynamics by low TC-complex concentrations in the absence of polymer mass changes demonstrates that microtubule dynamics are more sensitive to the actions of TC-complex than the polymer mass. Significant reduction of polymer mass occurred at relatively high TC-complex concentration (> 0.05 microM). However, the surviving microtubules were extremely stable. Thus, TC-complex stabilizes microtubules even though the microtubules can transiently depolymerize when TC-complex is added. The data also directly establish that kinetic suppression of dynamics by colchicine at low concentrations is effected by a low number of TC-complexes at the microtubule ends.

Animals↗
PubMed1993

Kinetic stabilization of microtubule dynamic instability in vitro by vinblastine.

The antiproliferative action of vinblastine at low concentrations appears to result from modulation of the polymerization dynamics of spindle microtubules rather than from depolarization of the microtubules [Jordan, M. A., Thrower, D., & Wilson, L. (1991) Cancer Res. 51, 2212-2222; (1992) J. Cell. Sci. 102, 401-416]. In the present study, we used differential interference contrast video microscopy to analyze the effects of vinblastine on the growing and shortening dynamics (dynamic instability) of individual bovine brain microtubules in vitro. With microtubules which were either depleted of microtubule-associated proteins (MAPs) or rich in MAPs, low concentrations of vinblastine (0.2 microM-1 microM) suppressed the growing and shortening rates and increased the percentage of time that the microtubules spent a state of attenuated activity, neither growing nor shortening detectably. Vinblastine also suppressed the duration of microtubule growing and shortening, and increased the duration of the attenuated state, during which the microtubules neither grew nor shortened detectably. Consistent with previous data obtained using radiolabeled nucleotide exchange in microtubule suspensions [Jordan, M. A., & Wilson, L. (1990) Biochemistry 29, 2730-2739], vinblastine suppressed growing and shortening dynamics at the kinetically more rapid plus ends. The results suggest that vinblastine kinetically stabilizes microtubule ends by modulating the gain and loss of the stabilizing GTP or GDP-Pi "cap", which is believed to be responsible for the transitions between the growing and shortening phases. The data support the hypothesis that (1) low concentrations of vinblastine inhibit mitosis by kinetically stabilizing the polymerization dynamics of spindle microtubules and that (2) the dynamics of spindle microtubules are critical for the proper progression of mitosis.

Animals↗
PubMed1993

Experimental molecular dynamics of an alanine-based helical peptide determined by spin label electron spin resonance.

The alanine-based 3K(I) peptide is reported to be very helical in aqueous solution. We have prepared a series of six nitroxide spin labeled analogs of the 3K(I) sequence and measured the variable-temperature ESR spectra for each in order to reveal the position-dependent peptide dynamics. From analysis of these local dynamics under helix-forming conditions at 1 degree C, we find that the helix termini show greater local dynamics than the peptide cancer. Further, the C-terminus is more mobile than the N-terminus. Even in the helix-promoting solvent trifluoroethanol, the results indicate that there is still substantially greater dynamics at the helix termini than at the peptide center. The unfolded state is also investigated, and we find that the peptide unfolded by guanidine hydrochloride is somewhat different than that found for high-temperature aqueous solution. Recently it was suggested that short 16-mer peptides may adopt a 3(10)-helix structure instead of the expected alpha-helix. The data presented here at 1 degree C show that there is sufficient disorder within the peptide to accommodate the 3(10) structure. Also calculated are the backbone torsional fluctuations, and the results compare well to those from computer molecular dynamics studies. A proposal is outlined that explains how the enhanced dynamics found at the C-terminus results from the exposure of the helix hydrogen bonds to aqueous solvent in this region of the peptide.

Alanine↗
PubMed1994

Effects of the tubulin-colchicine complex on microtubule dynamic instability.

The effects of the tubulin-colchicine complex (Tu-Col) on the dynamic behavior of microtubules have been examined under steady-state conditions in vitro. The addition of Tu-Col to tubulin microtubules at steady state results in only partial microtubule disassembly. Nevertheless, both the rate and the extent of tubulin exchange into microtubules are markedly suppressed by concentrations of Tu-Col which are low relative to the total amount of free tubulin. In addition, the time-dependent changes in microtubule length distribution, characteristic of dynamic instability, are suppressed by the addition of Tu-Col. Examination by video-enhanced dark-field microscopy of individual microtubules in the presence of Tu-Col shows that the principal effect of this complex is to reduce the growth rate at both ends of the microtubule. We have used computer simulation to rationalize the action of Tu-Col in terms of its effects on the experimentally observable parameters, namely, the rates of growth and shortening and the mean lifetimes of growth and shortening, which provide an empirical description of the dynamic behavior of microtubules. The results have been interpreted within the framework of the lateral cap formulation for microtubule dynamic instability [Martin, S. R., Schilstra, M. J., & Bayley, P. M. (1993) Biophys. J. 65, 578-596]. The simplest model mechanism requires only that Tu-Col binds to the microtubule end and inhibits further addition reactions in either the 5-start or the 8-start direction of the microtubule lattice. Monte Carlo simulations show that Tu-Col can, in this way, cause major suppression of the dynamic transitions of microtubules without inducing bulk microtubule disassembly. This type of mechanism could be important for the regulation of microtubule dynamics in vivo.

Colchicine↗
PubMed1987

Refinement of the solution structure of the DNA decamer 5'd(CTGGATCCAG)2: combined use of nuclear magnetic resonance and restrained molecular dynamics.

The solution structure of the self-complementary DNA decamer 5'd(CTGGATCCAG)2 comprising the specific target site for the restriction endonuclease BamH1 is investigated by using nuclear magnetic resonance sectroscopy and restrained molecular dynamics. With the exception of the H5'/H5" sugar proton resonances, all the nonexchangeable proton resonances are assigned sequentially by using pure-phase absorption two-dimensional nuclear Overhauser enhancement spectroscopy. From the time dependence of the nuclear Overhauser effects a set of 160 approximate interproton distances is determined and used as the basis of a structure refinement employing restrained molecular dynamics in which the interproton distances are incorporated into the total energy function of the system in the form of an effective potential term. Two restrained dynamics simulations are carried out, starting from classical B- and A-DNA [atomic root mean square (rms) difference 5.7 A]. In both cases convergence is achieved to very similar B-type structures with an atomic rms difference of 0.9 A which is comparable to the rms fluctuations of the atoms about their average positions. In addition, the rms difference between the experimental and calculated values of the interproton distances for both average restrained dynamics structures is approximately 0.3 A. These results suggest that the converged restrained molecular dynamics structures represent reasonable approximations of the solution structure. The average restrained dynamics structures exhibit clear sequence-dependent variations of torsion angles and helical parameters. In addition, the structures exhibit a small bend of around 10-20 degrees at the second (TpG) and eighth (CpA) base pair steps. This can be attributed to the positive base roll angles and large base pair slide values at the two Pyr-Pur steps. The central core of the decamer comprising the six-base recognition site for BamH1 (GGATCC), however, is straight.

DNA↗