Quasi-continuum models of twist-like and accordion-like low-frequency motions in DNA.

Formulae for calculating low-frequency twist-like and accordion-like modes of DNA molecules have been derived using a quasi-continuum model. The formulae can be employed in essentially all (viz. A, B, C, D, E, and Z) forms of DNA. Calculated results indicate that the experimentally observed low-frequency modes at 22 cm-1 for the A-form octanucleotide (d[CCCCGGGG]) and at 18 cm-1 for the B-form dodecanucleotide (d[CGCAA ATTTGCG]) may result from accordion-like motions, while those observed at 12 cm-1 and 15 cm-1 may result from combinations of twist-like oscillations excited in the intact segments of B- and A-DNA's, respectively. Frequency shifts in the low-frequency modes observed when DNA molecules undergo conformational changes among different forms are also discussed in terms of the current model.     

Investigation of low-frequency waves in plasma-filled microwave oscillators

The excitation of microwave oscillations by an electron beam in a hybrid plasma waveguide—a slow-wave structure (a sequence of inductively coupled resonators) with a plasma-filled transport channel—is studied both experimentally and theoretically. It is shown that the governing role in the generation of microwaves and their transmission to a feeder line is played by the spatial and temporal plasma-density variations associated with low-frequency ion plasma oscillations. The microwave pressure gives rise to low-frequency plasma oscillations with a rise time shorter than their period. This nonlinear mechanism for the excitation of low-frequency oscillations has a threshold in terms of the microwave power. The unsteady character of the spatial distribution of the plasma density results in intermittent microwave generation and shortens the duration of microwave pulses.     

Gapped DNA and cyclization of short DNA fragments

We use the cyclization of small DNA molecules, approximately 200 bp in length, to study conformational properties of DNA fragments with single-stranded gaps. The approach is extremely sensitive to DNA conformational properties and, being complemented by computations, allows a very accurate determination of the fragment's conformational parameters. Sequence-specific nicking endonucleases are used to create the 4-nt-long gap. We determined the bending rigidity of the single-stranded region in the gapped DNA. We found that the gap of 4 nt in length makes all torsional orientations of DNA ends equally probable. Our results also show that the gap has isotropic bending rigidity. This makes it very attractive to use gapped DNA in the cyclization experiments to determine DNA conformational properties, since the gap eliminates oscillations of the cyclization efficiency with the DNA length. As a result, the number of measurements is greatly reduced in the approach, and the analysis of the data is greatly simplified. We have verified our approach on DNA fragments containing well-characterized intrinsic bends caused by A-tracts. The obtained experimental results and theoretical analysis demonstrate that gapped-DNA cyclization is an exceedingly sensitive and accurate approach for the determination of DNA bending.     

Close correspondence between the motions from principal component analysis of multiple HIV-1 protease structures and elastic network modes

The large number of available HIV-1 protease structures provides a remarkable sampling of conformations of the different conformational states, which can be viewed as direct structural information about the dynamics of the HIV-1 protease. After structure matching, we apply principal component analysis (PCA) to obtain the important apparent motions for both bound and unbound structures. There are significant similarities between the first few key motions and the first few low-frequency normal modes calculated from a static representative structure with an elastic network model (ENM), strongly suggesting that the variations among the observed structures and the corresponding conformational changes are facilitated by the low-frequency, global motions intrinsic to the structure. Similarities are also found when the approach is applied to an NMR ensemble, as well as to molecular dynamics (MD) trajectories. Thus, a sufficiently large number of experimental structures can directly provide important information about protein dynamics, but ENM can also provide similar sampling of conformations.     

Theory of low-frequency vibrations in DNA macromolecules

To describe low-frequency dynamics of DNA macromolecules a model is developed taking into account the hydrogen bond stretching in base pairs, the backbone flexibility and intranucleoside mobility. For double-stranded DNA the normal vibrations are found and the structure of low-frequency spectrum is determined. The agreement between theory and Raman spectroscopy data for B-DNA is demonstrated. Conformational dependences of vibration spectrum during the B----A and helix----coil DNA transitions are studied. The contribution coming from low-frequency mobility to the nucleic-protein recognition processes is discussed.     

Cholinergic enhancement of visual attention and neural oscillations in the human brain

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex.     

Self-Excitation of Low-Frequency Oscillations in the Plasma Ring Formed by an ECR Discharge in a Narrow Coaxial Cavity

The conditions for the excitation of low-frequency oscillations in a plasma ring formed by an ECR discharge in a narrow coaxial cavity filled with argon were studied experimentally. The domain of the discharge parameters where these oscillations are stable is determined. It is supposed that the oscillations recorded are excited due to the appearance of an electrostatic wave propagating in the azimuthal direction.     

Nonrandom variability in respiratory cycle parameters of humans during stage 2 sleep

We analyzed breath-to-breath inspiratory time (TI), expiratory time (TE), inspiratory volume (VI), and minute ventilation (Vm) from 11 normal subjects during stage 2 sleep. The analysis consisted of 1) fitting first- and second-order autoregressive models (AR1 and AR2) and 2) obtaining the power spectra of the data by fast-Fourier transform. For the AR2 model, the only coefficients that were statistically different from zero were the average alpha 1 (a1) for TI, VI, and Vm (a1 = 0.19, 0.29, and 0.15, respectively). However, the power spectra of all parameters often exhibited peaks at low frequency (less than 0.2 cycles/breath) and/or at high frequency (greater than 0.2 cycles/breath), indicative of periodic oscillations. After accounting for the corrupting effects of added oscillations on the a1 estimates, we conclude that 1) breath-to-breath fluctuations of VI, and to a lesser extent TI and Vm, exhibit a first-order autoregressive structure such that fluctuations of each breath are positively correlated with those of immediately preceding breaths and 2) the correlated components of variability in TE are mostly due to discrete high- and/or low-frequency oscillations with no underlying autoregressive structure. We propose that the autoregressive structure of VI, TI, and Vm during spontaneous breathing in stage 2 sleep may reflect either a central neural mechanism or the effects of noise in respiratory chemical feedback loops; the presence of low-frequency oscillations, seen more often in Vm, suggests possible instability in the chemical feedback loops. Mechanisms of high-frequency periodicities, seen more often in TE, are unknown.     

Synchronous reversible alterations in enzymatic activity (conformational fluctuations) in actomyosin and creatine kinase preparations.

The phenomenon of synchronism of oscillations of actomyosin and creatine kinase activity in the whole volume of the enzyme preparations was analysed. The synchronous "conformational oscillations" were observed in concentrated gels of actomyosin and in diluted actomyosin and creatine kinase solutions (ATP-creatine N-phosphotransferase, EC 2.7.3.2). The macromolecules of proteins studied may be in two or four conformational states differing enzymatic activity. Large fluctuations become possible in a range of conditions wherein two or four different states, or conformers, are equiprobable. The synchronization of conformational changes of separate macromolecules is maintained with energy derived, for instance, from some oxidative process or dilution of the solution, the process being displayed as conformational oscillations.     

Molecular dynamics simulations of B-DNA: An analysis of the role of initial molecular configuration,randomly assigned velocity distribution,long integration times,and nonconstrained termini

Molecular dynamics simulations of three DNA sequences using the AMBER 3.0 force field were performed with implicit inclusion of water through a distance-dependent dielectric constant and solvated counterions. Simulations of the self-complementary DNA dodecamer d(CGCGAATTCGCG) were started from a regular B-DNA structure and the x-ray single crystal B-DNA structure. Although mean convergence during the 89-ps calculation was confirmed, localized differences in backbone torsionals and base-pair helicoidals were observed. A nanosecond simulation of the nonself-complementary 14 base-pair DNA d(GGCGGAATTGGCGG) indicates that most structural parameters stabilize within the first 100–200 ps, while isolated features show low-frequency oscillations throughout the calculation. The lack of harmonic constraints on the ends of the molecules was shown not to perturb the structural dynamics of the internal oligonucleotide beyond the external 2 base pairs. Comparison of three simulations of the nonself-complementary 14 base-pair DNA d(GGCGAAATTCGCGG), identical in all respects other than the assignment of initial Maxwellian atomic velocity distributions, revealed the inherent systematic variability. The three calculations result in nearly superimposable global structures, with localized variations in torsionals and helicoidals. Our results provide a basis for performing a comparative analysis of the effect of DNA sequence on localized structure. © 1993 John Wiley & Sons, Inc.     

Theory of Low-Frequency Vibrations in DNA Macromolecules

Abstract

To describe low-frequency dynamics of DNA macromolecules a model is developed taking into account the hydrogen bond stretching in base pairs, the backbone flexibility and intranucleoside mobility. For double-stranded DNA the normal vibrations are found and the structure of low- frequency spectrum is determined. The agreement between theory and Raman spectroscopy data for B-DNA is demonstrated. Conformational dependences of vibration spectrum during the B→A and helix→coil DNA transitions are studied. The contribution coming from low-frequency mobility to the nucleic-protein recognition processes is discussed.     

Normal-modes-based prediction of protein conformational changes guided by distance constraints

Based on the elastic network model, we develop a novel method that predicts the conformational change of a protein complex given its initial-state crystal structure together with a small set of pairwise distance constraints for the end state. The predicted conformational change, which is a linear combination of multiple low-frequency normal modes that are solved from the elastic network model, is computed as a response displacement induced by a perturbation to the system Hamiltonian that incorporates the given distance constraints. For a list of test cases, we find that the computed response displacement overlaps significantly with the measured conformational changes, when only a handful of pairwise constraints are used (相似文献   

Inconsistent link between low-frequency oscillations: R-R interval responses to augmented Mayer waves.

Low-frequency oscillations in arterial blood pressure (Mayer waves) and R-R interval are thought to be linked through the arterial baroreflex. To delve into this relationship, we applied low (10 mmHg) and moderate (30 mmHg) lower body negative pressure (LBNP) in 10-s cycles to 18 healthy young male subjects. They showed no change in average blood pressure with this oscillatory stimulus but did show a significant decrease in R-R interval (P < 0.05) during both levels of LBNP. In addition, we succeeded in augmenting low-frequency blood pressure oscillations in a graded response to oscillatory LBNP level (P < 0.05) while significantly increasing low-frequency R-R interval oscillations (P < 0.05). However, cross-spectral coherence between these increased oscillations was highly variable across individuals and stimulus level. Although nearly all subjects showed significant coherence during basal conditions (n = 17), only seven subjects maintained significant coherence during both levels of LBNP. These results suggest that a complex interaction of regulatory mechanisms determines the link between low-frequency oscillations and the responses to even low levels of LBNP.     

A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man alpha 1-3Man beta 1-4GlcNAc

A molecular mechanical force field is described for the conformational analysis of oligosaccharides. This force field has been derived by the addition of new parameters to the AMBER force field and is compatible with simulations of proteins. This new parametrization is assessed by comparison of the theoretically predicted conformations of Man alpha 1-3Man beta 1-4GlcNAc with the corresponding crystal structure. Molecular dynamics simulation data are presented for this structure both in vacuo and with the explicit inclusion of water molecules. While the former demonstrate significant torsional oscillations about glycosidic linkages at physiological temperature, in the latter these oscillations are highly damped due to the stabilizing influence of a "cage" of solvent-solvent and solvent-solute hydrogen bonds.     

Cardiac Rhythm Variability: Approaches to Mechanisms

Physiological mechanisms of cardiac rhythm variability (CRV) are reviewed. The results of original experiments are discussed together with the history of the problem and data available from the literature. Special emphasis is placed on the spectral analysis of cardiac rhythm. Various mechanisms of the generation of periodic and aperiodic components of CRV are considered. Although the variability of cardiac rhythm has been studied for many years in many laboratories worldwide, fine mechanisms of CRV remain obscure. However, a number of specific features of CRV are presently widely recognized. Periodic CRV components isolated from short-term records in patients at rest are represented by high-frequency, low-frequency, and very low-frequency oscillations. Fourier-transform spectral analysis of cardiac rhythm is the most appropriate method of the detection of these oscillations. High-frequency components are associated with respiration and represent the effects of the parasympathetic nervous system on myocardium. Low-frequency components are due to the activity of the postganglionic sympathetic fibers and represent the processes of cardiac rhythm modulation by the sympathetic nervous system. Genesis of very low-frequency oscillations is still uncertain. Most probably, these oscillations are associated with the effects of suprasegmental (primarily, hypothalamic) centers of autonomic regulation. Aperiodic CRV components represent random events associated with the reflex regulation of the heart rate by external or internal factors. Because aperiodic components significantly modify the results of the CRV analysis, the effects of these factors should be eliminated. It is concluded that because many problems associated with cardiac rhythm variability remain to be solved, extensive research in this direction should be continued.     

Low-frequency instability of an ion beam in the field of a high-current REB

A study is made of the linear and nonlinear stages of the low-frequency instability of an ensemble of ions that execute radial oscillations in the electric field of the space charge of an unneutralized high-current relativistic electron beam. Nonlinear mechanisms for stabilizing the low-frequency ion instability are considered. It is shown, in particular, that, under certain conditions, the development of the low-frequency instability can lead to the ejection of ions onto the walls of the drift chamber.     

DNA-induced conformational changes in type II restriction endonucleases: the structure of unliganded HincII

The 2.1A crystal structure of the unliganded type II restriction endonuclease, HincII, is described. Although the asymmetric unit contains only a single monomer, crystal lattice contacts bring two monomers together to form a dimer very similar to that found in the DNA bound form. Comparison with the published DNA bound structure reveals that the DNA binding pocket is expanded in the unliganded structure. Comparison of the unliganded and DNA liganded structures reveals a simple rotation of subunits by 11 degrees each, or 22 degrees total, to a more closed structure around the bound DNA. Comparison of this conformational change to that observed in the other type II restriction endonucleases where DNA bound and unliganded forms have both been characterized, shows considerable variation in the types of conformational changes that can occur. The conformational changes in three can be described by a simple rotation of subunits, while in two others both rotation and translation of subunits relative to one another occurs. In addition, the endonucleases having subunits that undergo the greatest amount of rotation upon DNA binding are found to be those that distort the bound DNA the least, suggesting that DNA bending may be less facile in dimers possessing greater flexibility.     

Computational modeling of epileptiform activities in medial temporal lobe epilepsy combined with <Emphasis Type="Italic">in vitro</Emphasis> experiments

Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson’s disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.