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At least 487 records · Page 27Linked to original sources

Depolarization-induced calcium responses in sympathetic neurons: relative contributions from Ca2+ entry, extrusion, ER/mitochondrial Ca2+ uptake and release, and Ca2+ buffering.

Many models have been developed to account for stimulus-evoked [Ca(2+)] responses, but few address how responses elicited in specific cell types are defined by the Ca(2+) transport and buffering systems that operate in the same cells. In this study, we extend previous modeling studies by linking the time course of stimulus-evoked [Ca(2+)] responses to the underlying Ca(2+) transport and buffering systems. Depolarization-evoked [Ca(2+)](i) responses were studied in sympathetic neurons under voltage clamp, asking how response kinetics are defined by the Ca(2+) handling systems expressed in these cells. We investigated five cases of increasing complexity, comparing observed and calculated responses deduced from measured Ca(2+) handling properties. In Case 1, [Ca(2+)](i) responses were elicited by small Ca(2+) currents while Ca(2+) transport by internal stores was inhibited, leaving plasma membrane Ca(2+) extrusion intact. In Case 2, responses to the same stimuli were measured while mitochondrial Ca(2+) uptake was active. In Case 3, responses were elicited as in Case 2 but with larger Ca(2+) currents that produce larger and faster [Ca(2+)](i) elevations. Case 4 included the mitochondrial Na/Ca exchanger. Finally, Case 5 included ER Ca(2+) uptake and release pathways. We found that [Ca(2+)](i) responses elicited by weak stimuli (Cases 1 and 2) could be quantitatively reconstructed using a spatially uniform model incorporating the measured properties of Ca(2+) entry, removal, and buffering. Responses to strong depolarization (Case 3) could not be described by this model, but were consistent with a diffusion model incorporating the same Ca(2+) transport and buffering descriptions, as long as endogenous buffers have low mobility, leading to steep radial [Ca(2+)](i) gradients and spatially nonuniform Ca(2+) loading by mitochondria. When extended to include mitochondrial Ca(2+) release (Case 4) and ER Ca(2+) transport (Case 5), the diffusion model could also account for previous measurements of stimulus-evoked changes in total mitochondrial and ER Ca concentration.

Animals↗

Diffusion-collision model for the folding kinetics of the lambda-repressor operator-binding domain.

The operator-binding domain of the lambda-repressor contains five alpha-helices and an extended N-terminal arm in the crystal structure determined by Pabo and Lewis reported in Nature 298, 443, 1982 (1). The four helices form a "box" enclosing a hydrophobic core with the fifth helix interacting with the equivalent helix in a dimer. With a small number of well-defined secondary structure elements (microdomains), the repressor is well suited for an analysis of its folding pathways and kinetics by use of the diffusion-collision model. In this paper, the basic elements of the model appropriate to a several microdomain protein are formulated and applied to a set of folding pathways consistent with the crystal structure of the operator-binding domain. The overall kinetics, as well as the time-dependence of intermediate states are determined as a function of the microdomain stability parameter.

Binding Sites↗

Kinetics and equilibrium studies for the adsorption of Acid Red 57 from aqueous solutions onto calcined-alunite.

The adsorption of Acid Red 57 (AR57) onto calcined-alunite was examined in aqueous solution in a batch system with respect to contact time, pH and temperature. The first-order, pseudo-second-order kinetic and the intraparticle diffusion models were used to describe the kinetic data and the rate constants were evaluated. The experimental data fitted very well the pseudo-second-order kinetic model and also followed the intraparticle diffusion model up to 90 min. The Langmuir and Freundlich adsorption models were applied to describe the equilibrium isotherms and the isotherm constants were also determined. The equilibrium data are successfully fitted to the Langmuir adsorption isotherm. The Langmuir isotherm constant, K(L), was used to evaluate the changes of free energy, enthalpy and entropy of adsorption for the adsorption of AR57 onto calcined-alunite. The results indicate that calcined-alunite could be employed as low-cost material for the removal of acid dyes from textile effluents.

Adsorption↗

[Tailed normal chromatographic peak expressed by plate model].

An equation for describing tailed normal chromatographic peak is derived based on the plate model. In terms of the de Moivre-Laplace theorem, which states that a binomial distribution can be approximated by the Gaussian distribution for large sample size, it is suggested that the concentration distribution along the distance downstream from the inlet of chromatographic column conforms to the Gaussian distribution function, but the concentration distribution with elution volume (or elution time) does not. The equation developed here, which is similar to the Gaussian distribution function, indicates that the normal chromatographic elution curve should be a tailing one. It is also shown that the symmetric Gaussian elution curve is an approximate solution of the plate model and can be obtained by the approximation of the equation here. The equation is proved to be congruent to the results of the diffusion model. Thus, the plate model and diffusion model are equivalent to each other in describing chromatographic process although different mechanism is based on.

English Abstract↗

Sparks and waves in a stochastic fire-diffuse-fire model of Ca2+ release.

Calcium ions are an important second messenger in living cells. Indeed, calcium signals in the form of waves have been the subject of much recent experimental interest. It is now well established that these waves are composed of elementary stochastic release events (calcium puffs or sparks) from spatially localized calcium stores. Here we develop a computationally inexpensive model of calcium release, based upon a stochastic generalization of the fire-diffuse-fire threshold model. Our model retains the discrete nature of calcium stores, but also incorporates a notion of release probability via the introduction of threshold noise. Numerical simulations of the model illustrate that stochastic calcium release leads to the spontaneous production of calcium sparks that may merge to form saltatory waves. In the parameter regime where deterministic waves exist, it is possible to identify a critical level of noise, defining a nonequilibrium phase transition between propagating and abortive structures. A statistical analysis shows that this transition is the same as for models in the directed percolation universality class. Moreover, in the regime where no initial structure can survive deterministically, threshold noise is shown to generate a form of array enhanced coherence resonance, whereby all calcium stores release periodically and simultaneously.

Biophysical Phenomena↗

A permeation-diffusion-reaction model of gas transport in cellular tissue of plant materials.

Gas transport in fruit tissue is governed by both diffusion and permeation. The latter phenomenon is caused by overall pressure gradients which may develop due to the large difference in O(2) and CO(2) diffusivity during controlled atmosphere storage of the fruit. A measurement set-up for tissue permeation based on unsteady-state gas exchange was developed. The gas permeability of pear tissue was determined based on an analytical gas transport model. The overall gas transport in pear tissue samples was validated using a finite element model describing simultaneous O(2), CO(2), and N(2) gas transport, taking into account O(2) consumption and CO(2) production due to respiration. The results showed that the model described the experimentally determined permeability of N(2) very well. The average experimentally determined values for permeation of skin, cortex samples, and the vascular bundle samples were (2.17+/-1.71)x10(-19) m(2), (2.35+/-1.96)x10(-19) m(2), and (4.51+/-3.12)x10(-17) m(2), respectively. The permeation-diffusion-reaction model can be applied to study gas transport in intact pears in relation to product quality.

Biological Transport↗

Computation of first passage time moments for stochastic diffusion processes modelling nerve membrane depolarization.

For further understanding of neural coding, stochastic variability of interspike intervals has been investigated by both experimental and theoretical neuroscientists. In stochastic neuronal models, the interspike interval corresponds to the time period during which the process imitating the membrane potential reaches a threshold for the first time from a reset depolarization. For neurons belonging to complex networks in the brain, stochastic diffusion processes are often used to approximate the time course of the membrane potential. The interspike interval is then viewed as the first passage time for the employed diffusion process. Due to a lack of analytical solution for the related first passage time problem for most diffusion neuronal models, a numerical integration method, which serves to compute first passage time moments on the basis of the Siegert recursive formula, is presented in this paper. For their neurobiological plausibility, the method here is associated with diffusion processes whose state spaces are restricted to finite intervals, but it can also be applied to other diffusion processes and in other (non-neuronal) contexts. The capability of the method is demonstrated in numerical examples and the relation between the integration step, accuracy of calculation and amount of computing time required is discussed.

Action Potentials↗

Fire-diffuse-fire model of dynamics of intracellular calcium waves.

When Ca2+ is released from internal stores in living cells, the resulting wave of increased concentration can travel without deformation (continuous propagation) or with burst-like behavior (saltatory propagation). We analyze the "fire-diffuse-fire" model in order to illuminate the differences between these two modes of propagation. We show that the Ca2+ release wave in immature Xenopus oocytes and cardiac myocytes is saltatory, whereas the fertilization wave in the mature oocyte is continuous.

Animals↗

Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.

Cardiac tissue engineering has made notable progress in recent years with the advent of an experimental model based on neonatal cardiomyocytes entrapped in collage gels and purified basement membrane extract, known as "engineered heart tissues" (EHTs). EHTs are a formidable display of tissue-level contractile function and cellular-level differentiation, although they suffer greatly from mass transport limitations due to the high density of metabolically active cells and the diffusion-limited nature of the hydrogel. In this report, a mathematical model was developed to predict oxygen levels inside a one-dimensional, diffusion-limited model of EHT. These predictions were then compared to values measured in corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs were cast between two plastic discs, which allowed for mass transfer with the culture medium to occur in only the radial direction. EHTs were cultured for up to 36 h in the presence of pimonidazole, after which time they were snap-frozen, histologically sectioned, and stained for bound pimonidazole. Quantitative image analysis was performed to measure the distance from the culture medium at which hypoxia first occurs under various conditions. As tested by variation of simple design parameters, the trends in oxygen profiles predicted by the model are in reasonable agreement with those obtained experimentally, although a number of ambiguities related to the specific model parameters led to a general overprediction of oxygen concentrations. Based on the sensitivity analysis in the present study, it is concluded that diffusion-reaction models may offer relatively precise predictions of oxygen concentrations in diffusion-limited tissue constructs.

Biological Transport↗

Estimating oxygen transport resistance of the microvascular wall.

The problem of diffusion of O(2) across the endothelial surface in precapillary vessels and its utilization in the vascular wall remains unresolved. To establish a relationship between precapillary release of O(2) and vascular wall consumption, we estimated the intravascular flux of O(2) on the basis of published in vivo measurements. To interpret the data, we utilized a diffusion model of the vascular wall and computed possible physiological ranges for O(2) consumption. We found that many flux values were not consistent with the diffusion model. We estimated the mitochondrial-based maximum O(2) consumption of the vascular wall (M(mt)) and a possible contribution to O(2) consumption of nitric oxide production by endothelial cells (M(NO)). Many values of O(2) consumption predicted from the diffusion model exceeded M(mt) + M(NO). In contrast, reported values of O(2) consumption for endothelial and smooth muscle cell suspensions and vascular strips in vitro do not exceed M(mt). We conjecture that most of the reported values of intravascular O(2) flux are overestimated, and the likely source is in the experimental estimates of convective O(2) transport at upstream and downstream points of unbranched vascular segments.

Animals↗

The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury.

A principal mechanism of calcium-mediated neuronal injury is the activation of neutral proteases known as calpains. Proteolytic substrates for calpain include receptor and cytoskeletal proteins, signal transduction enzymes and transcription factors. Recently, calpain inhibitors have been shown to provide benefit in rat models of focal head injury and focal cerebral ischemia. The present study sought to investigate, in experiment 1, the time course of calpain-mediated cytoskeletal injury in a mouse model of diffuse head injury by measuring the 150- and 145-kDa alpha-spectrin breakdown products (SBDP). Secondly, in experiment 2, we examined the effect of early (20 min postinjury) administration of the novel calpain inhibitor SJA6017 on functional outcome measured 24 h following injury and its effect on posttraumatic alpha-spectrin degradation. Lastly, in experiment 3, we examined the effect of delayed (4 or 6 h postinjury) administration of SJA6017 on 24-h postinjury functional outcome. In experiment 1, isoflurane-anesthetized male CF-1 mice (18-22 g) were subjected to a 750 g-cm weight drop-induced injury and were sacrificed for SBDP analysis at postinjury times of 30 min, and 1, 2, 6, 24 and 48 h (plus sham). In experiments 2 and 3, mice were injured as described, and delivered a single tail vein injection of either SJA6017 (0.3, 1, or 3 mg/kg) or vehicle (administered immediately, 4 or 6 h postinjury [3 mg/kg]). Functional outcome was evaluated in both studies, and, in experiment 2, 24-h postinjury assessment of SBDPs was determined. Following injury, the level of SBDP 145 was significantly different from sham at 24 and 48 h in cortical and at 24 h in the hippocampal tissues and at 48 h in the striatum. Immediate postinjury administration of SJA6017 resulted in a dose-related improvement in 24-h functional outcome (p < 0.05 at 3 mg/kg). Significance was maintained after a 4-h delay of the 3 mg/kg, but was lost after a 6-h delay. Despite improvement in functional outcome at 24 h, SJA6017 did not reduce spectrin breakdown in cortical or hippocampal tissues. These results support a role for calpain-mediated neuronal injury and the potential for a practical therapeutic window for calpain inhibition following traumatic brain injury. However, measurements of regional spectrin degradation may not be the most sensitive marker for determining the effects of calpain inhibition.

Animals↗

Intraparticle phosphorus diffusion in a drinking water treatment residual at room temperature.

Phosphorus (P) has been recognized as one of the major limiting nutrients that are responsible for eutrophication of surface waters, worldwide. Efforts have been concentrated on reducing P loads reaching water bodies, via surface runoff and/or leaching through a soil profile. Use of drinking water treatment residuals (WTRs) is an emerging cost-effective practice to reduce soluble P in poorly P-sorbing soils or systems high in P. Literature suggests that WTRs have huge P sorption capacities. We hypothesized that P sorption would be limited by diffusional constraints imposed by the WTR particles. Selected chemical and physical (specific surface area, particle size distribution) characteristics of an iron-based WTR were measured. Sorption P isotherms at room temperature were constructed, and sorption kinetics were monitored. An intraparticle diffusion model was utilized to fit the kinetic data. Results showed that the WTR dramatically reduced soluble P, showing nonequilibrium characteristics, even after 80 d of reaction. Specific surface area (SSA) measured with CO2 gas was significantly greater than the traditional BET-N2 value (28 versus 3.5 m2 g(-1)), suggesting that a large amount of internal surfaces might be present in the WTR. The intraparticle P diffusion model was modified to include the wide particle size distribution of the WTR. The intraparticle diffusion model fitted the data well (r2 = 0.83). We calculated a maximum apparent P diffusion coefficient value of 4 x 10(-15) cm2 s(-1), which agrees with published values for intraparticle diffusion in microporous sorbents. This work may be useful for predicting long-term sorption characteristics of WTRs, since WTRs have been suggested as potential long-term immobilizers of sorbed P in P-sensitive ecosystems.

Adsorption↗

Lysozyme extraction from egg white using reverse micelles in a Graesser contactor: mass transfer characterization.

The gentle mixing characteristics of a Graesser contactor can help to avoid the formation of stable emulsions, which is one advantage of this type of contactor when used with reversed micellar extraction. In this study, the performance of the Graesser contactor in lysozyme extraction from hen egg white is investigated. The concentration profile of lysozyme in the aqueous and organic phases indicated that, while substantial axial mixing occurred in the contactor, the extraction yield was in the range of 97% to 99%. The number of mass transfer units (N(ox)) was determined using a diffusion model, and the influence of aqueous-to-organic phase flow ratio, rotor speed, and total throughput on contactor performance was studied. It was found that the diffusion model could describe quite well the extraction of lysozyme from hen egg white using reversed micelles. The optimal conditions for the extraction at steady state were found to be a rotor speed of 5 rpm, an aqueous-to-organic phase flow ratio of 60:20 mL/min, and a total throughput of 80 mL/min. In addition, back-extraction was also performed using the conventional method (1.5 M KBr at pH 11.5) in the contactor. It was found that this mass transfer was not well described by a diffusion model, although 85% of the lysozyme could be recovered with the operating conditions used: a rotor speed of 10 rpm, and an aqueous-to-organic flow rate of 10:10 mL/min.

Biotechnology↗

[Model of diffuse axonal injury and focal brain injury in rats].

OBJECTIVE: To establish a rather ideal experimental brain injury model in rats, in which diffuse axonal injury(DAI) and focal brain contusion were made concurrently. METHODS: The pathophysiological changes were monitored, and the histological changes were observed under naked eye, microscope and electric microscope. RESULTS: 1. The mortality in the group suffering from DAI with focal contusion(Group A) was much higher than that in DAI(Group B) and sham group(Group C); 2. The time of post-injury primary coma in Group A [(5.19 +/- 0.49) h] was longer than that in Group B [(2.75 +/- 0.16) h] and Group C [(2.77 +/- 0.20) h] significantly(P < 0.01); 3. Immunohistological examination showed that the diffuse axonal injury could be seen in several parts of the brain(subcortical, corpus callosum and brainstem) in Group A; 4. We observed in Group A under electric microscope that the axons were swollen and degenerated fragmently, neurofilaments ranged disorderly and there was vacuolation. CONCLUSION: The model is cheap, simple and can be easily repeated. Furthermore it can be used to research the changes of pathophysiology, histology and moleculobiochemistry of head injury in human beings.

Animals↗

The in vitro permeability coefficient and short-term absorption rates for vinyl toluene using human cadaver skin mounted in a static diffusion cell model.

Vinyl toluene is one of several methylstyrene monomers that provide improved performance in resins for specialty paints, hydrocarbon resins for adhesives, specialty polymers, and unsaturated polyester resins. The purpose of this study was to determine a permeability coefficient (Kp) and short-term absorption rate for vinyl toluene using human cadaver skin mounted in an in vitro static diffusion cell model with an exposure area of 0.64 cm2. For the Kp determination, vinyl toluene was applied at a rate of 100 microL/cm2 to 6 skin replicates representing 4 human subjects. Serial receptor fluid samples were collected at 1, 2, 4, 8, 12, 24, 36, and 48 h postapplication and analyzed for vinyl toluene by HPLC-UV. Based on the slope at steady-state (203.3 microg cm(-2) h(-1) +/- 120.0 microg cm(-2) h(-1)) and the concentration of the applied dose of vinyl toluene, taken as its density (894,600 microg/cm3), the Kp was calculated to be 2.27 x 10(-4) cm/h (+/-1.34 x 10(-4) cm/h). For the short-term absorption experiments, 12 skin replicates representing 3 human subjects were employed. Following 10- and 60-min exposures to a finite dose of vinyl toluene (10 microL/cm2), the respective short-term absorption rates were calculated to be 66.0 (+/-29.9) and 104.2 (+/-63.0) microg cm(-2) h(-1). These data provide industrial hygienists and safety personnel values to estimate the amount of vinyl toluene that may be absorbed via the dermal exposure route, given a variety of exposure scenarios, and the time it takes (skin absorption time) to reach a body burden equal to the Occupational Safety and Health Administrative permissible exposure level (OSHA PEL) or ACGIH TLV.

Cadaver↗

Film rupture in the diffuse interface model coupled to hydrodynamics.

The process of dewetting of a thin liquid film is usually described using a long-wave approximation yielding a single evolution equation for the film thickness. This equation incorporates an additional pressure term-the disjoining pressure-accounting for the molecular forces. Recently a disjoining pressure was derived coupling hydrodynamics to the diffuse interface model [L. M. Pismen and Y. Pomeau, Phys. Rev. E 62, 2480 (2000)]. Using the resulting evolution equation as a generic example for the evolution of unstable thin films, we examine the thickness ranges for linear instability and metastability for flat films, the families of stationary periodic and localized solutions, and their linear stability. The results are compared to simulations of the nonlinear time evolution. From this we conclude that, within the linearly unstable thickness range, there exists a well defined subrange where finite perturbations are crucial for the time evolution and the resulting structures. In the remainder of the linearly unstable thickness range the resulting structures are controlled by the fastest flat film mode assumed up to now for the entire linearly unstable thickness range. Finally, the implications for other forms of disjoining pressure in dewetting and for spinodal decomposition are discussed.

Journal Article↗