SEARCH · PubMed Health

Results for “trajectory analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed2002

Solution structure of a pentasaccharide representing the repeating unit of the O-antigen polysaccharide from Escherichia coli O142: NMR spectroscopy and molecular simulation studies.

Conformational studies have been performed of a pentasaccharide derived from the O-polysaccharide from Escherichia coli O142. The polymer was selectively degraded by anhydrous hydrogen fluoride and reduced to yield an oligosaccharide model of its repeating unit, which in the branching region consists of four aminosugars. A comparison of (1)H and (13)C chemical shifts between the pentasaccharide and the polymer showed only minor differences, except where the cleavage had taken place, indicating that the oligomer is a good model of the repeating unit. Langevin dynamics and molecular dynamics simulations with explicit water molecules were carried out to sample the conformational space of the pentasaccharide. For the glycosidic linkages between the hexopyranoside residues, small but significant changes were observed between the simulation techniques. One-dimensional (1D) (1)H,(1)H double pulsed field gradient spin echo (DPFGSE) transverse rotating-frame Overhauser effect spectroscopy (T-ROESY) experiments were performed, and homonuclear cross-relaxation rates were obtained. Subsequently, a comparison of interproton distances from NMR experiment and the two simulation approaches showed that in all cases the use of explicit water in the simulations resulted in better agreement. Hydrogen-bond analysis of the trajectories from the molecular dynamics simulation revealed interresidue interactions to be important as a cluster of different hydrogen bonds and as a distinct highly populated hydrogen bond. NMR data are consistent with the presence of hydrogen bonding within the model of the repeating unit.

Carbon Isotopes↗

PubMed1985

Light microscopic observations on cat Renshaw cells after intracellular staining with horseradish peroxidase. I. The axonal systems.

Five intracellularly HRP-stained Renshaw cells were subjected to light microscopic analysis of the trajectories, branching patterns, and projections of the axonal systems. The cell bodies were located ventrally in lamina VII. In three neurons the axon originated from the cell body and in the remaining two cells from a dendrite. After a 600-870-microns distance the axons entered the ventral funiculus, where all of them continued rostrally. Two axons also gave off a caudal branch in the funiculus. The diameters of the main axons varied between 2.1 and 10.0 microns. The main axons gave off one to four first-order collaterals before entering the ventral funiculus and up to three collaterals could be seen to originate from the same node of Ranvier. In the ventral funiculus up to five first-order collaterals could be traced from the same main axon. The axon collateral trees were often very extensive and daughter branches up to the 22nd order were observed. The distance between two successive branching points varied between 4 and 410 microns. A large number of boutonlike swellings were found along (59%) or at the ends of the collateral branches. At the most, 1,278 swellings originated from a single axon collateral tree. Most of the swellings were located in lamina IX, but they also appeared ventrally and dorsolaterally in lamina VII.

Animals↗

PubMed1990

Development of compartmentalized innervation of the rat gluteus maximus muscle.

The innervation territories of the nerves to the gluteus maximus muscle were investigated in neonatal rats by using evoked electromyographic mapping techniques. Similar methods were employed to determine the terminal fields of individual motoneurons. Both at birth and after the period of neuromuscular synapse elimination, rat gluteus maximus is partitioned by its two muscle nerves. Each of these partitions is further divided into neuromuscular compartments by the primary branches of the muscle nerves. The terminal fields of individual motoneurons are about as well localized in early neonates as in 26 day-old animals. Intracellular records from gluteal muscle cells reveal that some myotubes in a narrow region near the center of the muscle receive inputs from both of the muscle nerves during the period of polyneuronal innervation. Such cross-compartmental innervation could be demonstrated only until the eighth postnatal day, even though polyneuronally innervated muscle cells were found as late as postnatal day 18. Analysis of the trajectories of individual axons filled with horseradish peroxidase indicates that they branch into only one primary branch of the nerves to gluteus maximus, both in newborn and 14 day-old pups. The innervation of gluteus maximus at birth is essentially restricted to neuromuscular compartments. Synapse elimination probably plays a minor role in establishing neuromuscular compartments.

Aging↗

PubMed2005

Dystroglycan is involved in laminin-1-stimulated motility of Müller glial cells: combined velocity and directionality analysis.

We investigate the role of dystroglycan, a major laminin-1 receptor and central member of the dystrophin-glycoprotein complex, in the laminin-1 induced motility of cultured Muller glial cells. Binding of laminin-1 to dystroglycan was prevented by IIH6, a function-blocking monoclonal antibody against alpha-dystroglycan. As an alternative means of inhibition, we used heparin to mask the dystroglycan binding site of the laminin-1, known to overlap with heparin binding sites. Cell motility was characterized in a two-dimensional motility assay based on computer-controlled videomicroscopy and statistical analysis of cellular trajectories. We obtained data on both the cell velocity and the diffusion index, a measure of direction-changing frequency. Both means of inhibition of dystroglycan function led to a significant decrease in the ability of laminin-1 to stimulate cell migration. At the same time, dystroglycan function does not appear to be involved in laminin-1-dependent increase in process dynamism and direction-changing activity.

Animals↗

PubMed2006

Single molecule fluorescence imaging of the photoinduced conversion and bleaching behavior of the fluorescent protein Kaede.

Photoconversion and photobleaching behavior of the fluorescent protein Kaede immobilized in polyacrylamide gel matrix at room temperature was studied by single molecule wide-field fluorescence microscopy. Photobleaching kinetics of Kaede molecules upon excitation at 488 nm showed slight heterogeneity, suggesting the presence of different protein conformations and/or the distribution of local environments in the gel matrix. Statistical analysis of intensity trajectories of single molecules revealed four major types of fluorescence dynamics behavior upon short illumination by a violet light pulse (405 nm). In particular, two types of photoswitching behavior were observed: the green-to-red photoconversion (4% of Kaede molecules) and the photoactivation of green fluorescence without emission of red fluorescence (13%). Two other major groups show neither photoconversion nor red emission and demonstrate photoinduced partial deactivation (43%) and partial revival (30%) of green fluorescence. The significantly lower green-to-red conversion ratio as compared with bulk measurements in aqueous solution might be induced by the immobilization of the protein molecules within a polyacrylamide gel. Contrary to Ando et al. (Proc Natl Acad Sci 2002;99:12651-12656), we found a significant increase in green fluorescence emission upon illumination with 405-nm light, which is typical for GFP and related proteins.

Animals↗

PubMed1996

Bending of the calmodulin central helix: a theoretical study.

The crystal structure of calcium-calmodulin (CaM) reveals a protein with a typical dumbbell structure. Various spectroscopic studies have suggested that the central linker region of CaM, which is alpha-helical in the crystal structure, is flexible in solution. In particular, NMR studies have indicated the presence of a flexible backbone between residues Lys 77 and Asp 80. This flexibility is related directly to the function of the protein because it enables the N- and C-terminal domains of the protein to move toward each other and bind to the CaM-binding domain of a target protein. We have investigated the flexibility of the CaM central helix by a variety of computational techniques: molecular dynamics (MD) simulations, normal mode analysis (NMA), and essential dynamics (ED) analysis. Our MD results reproduce the experimentally determined location of the bend in a simulation of only the CaM central helix, indicating that the bending point is an intrinsic property of the alpha-helix, for which the remainder of the protein is not important. Interestingly, the modes found by the ED analysis of the MD trajectory are very similar to the lowest frequency modes from the NM analysis and to modes found by an ED analysis of different structures in a set of NMR structures. Electrostatic interactions involving residues Arg 74 and Asp 80 seem to be important for these bending motions and unfolding, which is in line with pH-dependent NMR and CD studies.

Amino Acid Sequence↗

PubMed1997

OLDERADO: on-line database of ensemble representatives and domains. On Line Database of Ensemble Representatives And DOmains.

In cases where the structure of a single protein is represented by an ensemble of conformations, there is often a need to determine the common features and to choose a "representative" conformation. This occurs, for example, with structures determined by NMR spectroscopy, analysis of the trajectory from a molecular dynamics simulation, or an ensemble of structures produced by comparative modeling. We reported previously automatic methods for (1) defining the atoms with low spatial variance across an ensemble (i.e., the "core" atoms) and the domains in which these atoms lie, and (2) clustering an ensemble into conformationally related subfamilies. To extend the utility of these methods, we have developed a freely available server on the World Wide Web at http:/(/)neon.chem.le.ac.uk/olderado/. This (1) contains an automatically generated database of representative structures, core atoms, and domains determined for 449 ensembles of NMR-derived protein structures in the Protein Data Bank (PDB) in May 1997, and (2) allows the user to upload a PDB-formatted file containing the coordinates of an ensemble of structures. The server returns in real time: (1) information on the residues constituting domains: (2) the structures that constitute each conformational subfamily; and (3) an interactive java-based three-dimensional viewer to visualise the domains and clusters. Such information is useful, for example, when selecting conformations to be used in comparative modeling and when choosing parts of structures to be used in molecular replacement. Here we describe the OLDERADO server.

Computer Communication Networks↗

PubMed2004

Probing flexibility and "induced-fit" phenomena in aldose reductase by comparative crystal structure analysis and molecular dynamics simulations.

Aldose reductase is a promising target for the treatment of diabetic complications, and as such, has become the focus of various drug design projects. As revealed by a survey of available crystal structures, the protein shows pronounced induced-fit effects upon ligand binding. Although helping to explain the enzyme's substrate promiscuity, phenomena of this kind are still responsible for significant complications in structure-based design efforts directed to aldose reductase. Accordingly, a deeper understanding of the principles governing conformational alterations in this enzyme would be of utmost practical importance. As a first step in addressing this issue, molecular dynamics (MD) simulations have been carried out. The ultrahigh resolution crystal structure of aldose reductase complexed with inhibitor IDD594 served as ideal starting point for a set of different simulations of nanosecond time scale: the native complexed state with bound inhibitor, the uncomplexed state (after removal of the inhibitor) at standard temperature, and the uncomplexed state at elevated temperature. The reference simulation of the complex exhibits extraordinary stability of the overall fold, whereas two distinct conformational substates are found for the binding-site region. In contrast, already at standard temperature pronounced changes are observed in the binding region during the simulation of the uncomplexed state. Leu300, for example, closes the access to the pocket opened by IDD594. On the other hand, conformations around the catalytic site are highly conserved, with the His110-Tyr48-NADP+ orientation being stabilized by a water molecule. Detailed analysis of the trajectories allows to reveal a set of distinct conformational substates that may prove useful as alternative structural templates in virtual screening for new aldose reductase inhibitors.

Acetates↗

PubMed2004

Structural and dynamic effects of alpha-helix deletion in Sso7d: implications for protein thermal stability.

Sso7d is a 62-residue protein from the hyperthemophilic archaeon Sulfolobus solfataricus with a denaturation temperature close to 100 degrees C around neutral pH. An engineered form of Sso7d truncated at leucine 54 (L54Delta) is significantly less stable, with a denaturation temperature of 53 degrees C. Molecular dynamics (MD) studies of Sso7d and its truncated form at two different temperatures have been performed. The results of the MD simulations at 300 K indicate that: (1) the flexibility of Sso7d chain at 300 K agrees with that detected from X-ray and NMR structural studies; (2) L54Delta remains stable in the native folded conformation and possesses an overall dynamic behavior similar to that of the parent protein. MD simulations performed at 500 K, 10 ns long, indicate that, while Sso7d is in-silico resistant to high temperature, the truncated variant partially unfolds, revealing the early phases of the thermal unfolding pathway of the protein. Analysis of the trajectories of L54Delta suggests that the unzipping of the N-terminal and C-terminal beta-strands should be the first event of the unfolding pathway, and points out the regions more resistant to thermal unfolding. These findings allow one to understand the role played by specific interactions connecting the two ends of the chain for the high thermal stability of Sso7d, and support recent hypotheses on its folding mechanism emerged from site-directed mutagenesis studies.

Amino Acids↗

PubMed1994

Primary mesenchyme cell migration in the sea urchin embryo: distribution of directional cues.

The directional migration of the primary mesenchyme cells (PMCs) of the sea urchin embryo is a critical step in the process of gastrulation. Although interactions between the migrating cells and the blastocoel environment are necessary for guiding the PMCs to their subequatorial target site, the nature of these interactions and the localization of guidance cues involved in directing the cells are not yet known. Previous studies have suggested that PMC migration is the result of random exploration and selective trapping at the target site by a pattern of adhesiveness in the ectoderm or basal lamina. To better characterize the distribution of guidance cues in the blastocoel we used a combination of time-lapse microscopy, microsurgery, and fluorescence photoablation to study the behavior of the migrating cells. By using fluorescence time-lapse microscopy, and a two-dimensional random-walk analysis of cell trajectories, we demonstrated that fluorescently labeled PMCs injected near the animal pole move in a directed fashion over a relatively long distance to reach the target site. This suggests that guidance cues are distributed globally throughout the embryo and are not restricted to the immediate ring area. To further test this hypothesis we investigated the migratory behavior of PMCs that were prevented from interacting directly with the target site. First, we examined the behavior of PMCs injected into animal embryo fragments lacking the target site. We found that PMCs move to the vegetal-most area of such embryo fragments, regardless of their size. Second, we studied the effects of photoablating a stripe of ectoderm between PMCs injected at the animal pole region (APR) and the target site. PMCs were found to accumulate along the ablated stripe and were unable to cross it for up to 6 hr after ablation. We also examined the migratory behavior of endogenous PMCs in embryos treated with lithium, a vegetalizing agent which shifts the position of the PMC ring toward the animal pole. We found that PMCs accumulated along an ablated stripe of ectoderm positioned below the shifted target site, suggesting that endogenous PMCs follow a set of directional cues to the target site which may be similar to those used by PMCs injected into the APR. As a whole, these results suggest that migrating PMCs follow a set of directional cues that are widely distributed throughout the blastocoel and that may be arranged in a gradient.

Animals↗

PubMed1996

Dynamic contributions to the DNA binding entropy of the EcoRI and EcoRV restriction endonucleases.

Molecular Dynamics simulations on DNA-EcoRI and DNA-EcoRV complexes suggest that the DNA within these complexes is significantly more ordered than free DNA. Similarly, both the protein and the DNA are more ordered in the specific (cognate) DNA-EcoRV complex than they are in the non-cognate DNA-protein complex, consistent with recently proposed analogies between protein folding and sequence-specific DNA-protein recognition. Analysis of the trajectories shows that the net entropy gain upon specific binding to be the result of opposing contributions. Solvent release, which increases entropy versus configurational terms (as measured by the magnitude of the atomic fluctuations), and collective terms from tight coupling between the motions of the protein and the DNA.

Computer Simulation↗

PubMed2001

Role of native topology investigated by multiple unfolding simulations of four SH3 domains.

The relative importance of amino acid sequence and native topology in the unfolding process of two SH3 domains and two circular permutants was investigated by 120 molecular dynamics runs at 375 K for a total simulation time of 0.72 micros. The alpha-spectrin (aSH3) and src SH3 (sSH3) domains, which have the same topology and a sequence identity of only 34%, show similar unfolding pathways. The disappearance of the three-stranded antiparallel beta-sheet is the last unfolding event, in agreement with a large repertoire of kinetic data derived from point mutations as well as glycine insertions and disulfide crosslinks. Two alternative routes of beta-sheet unfolding have emerged from the analysis of the trajectories. One is statistically preferred in aSH3 (n-src loop breaks before distal hair-pin) and the inverse in sSH3. An elongation of the beta2-beta3 hairpin was observed during the unfolding of sSH3 at 375 K and in 300 K simulations started from the putative transition state of sSH3 in accord with unusual kinetic data for point mutations at the n-src loop. The change of connectivity in the permutants influenced the sequence of unfolding events mainly at the permutation site. Regions where the connectivity remained unaffected showed the same chronology of contact disappearance. Taken together with previous folding simulations of two designed three-stranded antiparallel beta-sheet peptides, these results indicate that, at least for small beta-sheet proteins, the folding mechanism is primarily defined by the native state topology, whilst specific interactions determine the statistically predominant folding route.

Amino Acid Sequence↗

PubMed1992

Charisma, crowd psychology and altered states of consciousness.

This paper argues that an interpretive meaning-centered analysis is not adequate for understanding collective behavior that is outside the range of calculating rationality. Alternative approaches to collective irrational action are drawn from the work of Weber and Durkheim, as well as from the crowd psychologists Le Bon and Tarde. These approaches are then illustrated in a short analysis of the trajectories and recruitment techniques of two contemporary American religious annunications: est and Scientology, and the findings applied to the general social formation.

Consciousness↗

PubMed1994

Molecular dynamics simulation of a phospholipid membrane.

We present the results of molecular dynamics (MD) simulations of a phospholipid membrane in water, including full atomic detail. The goal of the simulations was twofold: first we wanted to set up a simulation system which is able to reproduce experimental results and can serve as a model membrane in future simulations. This goal being reached it is then further possible to gain insight in to those properties that are experimentally more difficult to access. The system studied is dipalmitoylphosphatidylcholine/water, consisting of 5408 atoms. Using original force field parameters the membrane turned out to approach a gel-like state. With slight changes of the parameters, the system adopted a liquid-crystalline state. Separate 80 ps runs were performed on both the gel and liquid-crystalline systems. Comparison of MD results with reliable experimental data (bilayer repeat distance, surface area per lipid, tail order parameters, atom distributions) showed that our simulations, especially the one in the liquid-crystalline phase, can serve as a realistic model for a phospholipid membrane. Further analysis of the trajectories revealed valuable information on various properties. In the liquid-crystalline phase, the interface turns out to be quite diffuse, with water molecules penetrating into the bilayer to the position of the carbonyl groups. The 10-90% width of the interface turns out to be 1.3 nm and the width of the hydrocarbon interior 3.0 nm. The headgroup dipoles are oriented at a small angle with respect to the bilayer plane. The resulting charge distribution is almost completely cancelled by the water molecules. The electron density distribution shows a large dip in the middle of the membrane. In this part the tails are more flexible. The mean life time between dihedral transitions is 20 ps. The average number of gauche angles per tail is 3.5. The occurrence of kinks is not a significant feature.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

In vitro analysis of neuron-glial cell interactions during cellular migration.

We used time-lapse microscopy to study the in vitro migration of neuronal cells from developing chick ciliary ganglion. These cells, when dissociated and cultured in a chemically defined medium, are able to migrate and to associate into clusters. We focused our attention on the study of the distribution of neuronal velocity components. Quantitative analysis of cell trajectories allowed us to demonstrate that, in many cells, velocities are well described by the Langevin equation, when deterministic components of the forces acting on the cells are taken into account. We also have shown that the majority of neurons whose movement is not purely random migrate in association with glial cells. We conclude that glial cells, by guiding neurons during migration, play an important role in the cell organization in vitro.

Animals↗

PubMed2005

Geometric properties of a class of piecewise affine biological network models.

The purpose of this report is to investigate some dynamical properties common to several biological systems. A model is chosen, which consists of a system of piecewise affine differential equations. Such a model has been previously studied in the context of gene regulation and neural networks, as well as biochemical kinetics. Unlike most of these studies, nonuniform decay rates and several thresholds per variable are assumed, thus considering a more realistic model. This model is investigated with the aid of a geometric formalism. We first provide an analysis of a continuous-space, discrete-time dynamical system equivalent to the initial one, by the way of a transition map. This is similar to former studies. Especially, the analysis of periodic trajectories is carried out in the case of multiple thresholds, thus extending previous results, which all concerned the restricted case of binary systems. The piecewise affine structure of such models is then used to provide a partition of the phase space, in terms of explicit cells. Allowed transitions between these cells define a language on a finite alphabet. Some words are proved to be forbidden in this language, thus improving the knowledge on such systems in terms of symbolic dynamics. More precisely, we show that taking these forbidden words into account leads to a dynamical system with strictly lower topological entropy. This holds for a class of systems, characterized by the presence of a splitting box, with additional conditions. We conclude after an illustrative three-dimensional example.

Algorithms↗

PubMed2004

Molecular aspects of the interaction between amphotericin B and a phospholipid bilayer: molecular dynamics studies.

Amphotericin B (AmB) is a polyene macrolide antibiotic used to treat systemic fungal infections. The molecular mechanism of AmB action is still only partly characterized. AmB interacts with cell-membrane components and forms membrane channels that eventually lead to cell death. The interaction between AmB and the membrane surface can be regarded as the first (presumably crucial) step on the way to channel formation. In this study molecular dynamics simulations were performed for an AmB-lipid bilayer model in order to characterize the molecular aspects of AmB-membrane interactions. The system studied contained a box of 200 dimyristoylphosphatidylcholine (DMPC) molecules, a single AmB molecule placed on the surface of the lipid bilayer and 8,065 water molecules. Two molecular dynamics simulations (NVT ensemble), each lasting 1 ns, were performed for the model studied. Two different programs, CHARMM and NAMD2, were used in order to test simulation conditions. The analysis of MD trajectories brought interesting information concerning interactions between polar groups of AmB and both DMPC and water molecules. Our studies show that AmB preferentially took a vertical position, perpendicular to the membrane surface, with no propensity to enter the membrane. Our finding may suggest that a single AmB molecule entering the membrane is very unlikely.

Amphotericin B↗

PubMed1989

Penetrating wounds to the heart: a wartime experience.

Forty-nine war casualties with penetrating cardiac wounds were treated at the Hôtel-Dieu de France University Hospital between April 1975 and December 1987. All the wounds were caused by high-velocity missiles. An aggressive approach was utilized. Emergency room thoracotomy was performed in 17 "lifeless" patients, 4 of whom survived. Twenty-seven of the 32 patients who were in stable enough condition to undergo initial repair in the operating room survived. Overall survival was 63% (31/49). No intracardiac injuries were diagnosed in survivors, and no cardiac reoperations were required. Careful analysis of the trajectory of the missile or missiles and a portable chest roentgenogram were the most important factors for diagnosing a penetrating wound to the heart and for predicting potential associated injuries.

Adolescent↗