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PubMed1989

The actions of Neurospora endo-exonuclease on double strand DNAs.

Neurospora crassa endo-exonuclease, an enzyme implicated in recombinational DNA repair, was found previously to have a distributive endonuclease activity with a high specificity for single strand DNA and a highly processive exonuclease activity. The activities of endo-exonuclease on double strand DNA substrates have been further explored. Endo-exonuclease was shown to have a low bona fide endonuclease activity with completely relaxed covalently closed circular DNA and made site-specific breaks in linear double strand DNA at a low frequency while simultaneously generating a relatively high level of single strand breaks (nicks) in the DNA. Sequencing at nicks induced by endo-exonuclease in pBR322 restriction fragments showed that the highest frequency of nicking occurred at the mid-points of two sites with the common sequence, p-AGCACT-OH. In addition, sequencing revealed less frequent nicking at identical or homologous hexanucleotide sequences in all other 54 cases examined where these sequences either straddled the break site itself or were within a few nucleotides on either side of the break site. The exonucleolytic action of endo-exonuclease on linear DNA showed about 100-fold preference for acting in the 5' to 3' direction. Removal of the 5'-terminal phosphates substantially reduced this activity, internal nicking, and the ability of endo-exonuclease to generate site-specific double strand breaks. On the other hand, nicking of the dephosphorylated double strand DNA with pancreatic DNase I stimulated the exonuclease activity by almost 5-fold, but no stimulation was observed when the DNA was nicked by Micrococcal nuclease. Thus, 5'-p termini either at double strand ends or at nicks in double strand DNA are entry points to the duplex from which endo-exonuclease diffuses linearly or "tracks" in the 5' to 3' direction to initiate its major endo- and exonucleolytic actions. The results are interpreted to show how it is possible for endo-exonuclease to generate single strand DNA for switching into a homologous duplex either at a nick or while remaining bound at a double strand break in the DNA. Such mechanisms are consistent with current models for recombinational double strand break repair in eukaryotes.

Base Composition↗
PubMed2002

Role of magnesium in the reduction of ischemic depolarization and lesion volume after experimental subarachnoid hemorrhage.

OBJECT: Ischemia-induced tissue depolarizations probably play an important role in the pathophysiology of cerebral ischemia caused by parent vessel occlusion. Their role in ischemia caused by subarachnoid hemorrhage (SAH) remains to be investigated. The authors determined whether ischemic depolarizations (IDs) or cortical spreading depressions (CSDs) occur after SAH, and how these relate to the extent of tissue injury measured on magnetic resonance (MR) images. In addition, they assessed whether administration of MgSO4 reduces depolarization time and lesion volume. METHODS: By means of the endovascular suture model, experimental SAH was induced in 52 rats, of which 37 were appropriate for analysis, including four animals that underwent sham operations. Before induction of SAH, serum Mg++ levels were measured and 90 mg/kg intravascular MgSO4 or saline was given. Extracellular direct current potentials were continuously recorded from six Ag/AgCl electrodes, before and up to 90 minutes following SAH, after which serum Mg++ levels were again measured. Next, animals were transferred to the MR imaging magnet for diffusion-weighted (DW) MR imaging. Depolarization times per electrode were averaged to determine a mean depolarization time per animal. No depolarizations occurred in sham-operated animals. Ischemic depolarizations occurred at all electrodes in all animals after SAH. Only two animals displayed a single spreading depression-like depolarization. The mean duration of the ID time was 41 +/- 25 minutes in the saline-treated controls and 31 +/- 30 minutes in the Mg++-treated animals (difference 10 minutes: p = 0.31). Apparent diffusion coefficient (ADC) maps of tissue H2O, obtained using DW images approximately 2.5 hours after SAH induction, demonstrated hypointensities in both hemispheres, but predominantly in the ipsilateral cortex. No ADC abnormalities were found in sham-operated animals. The mean lesion volume, as defined on the basis of a significant ADC reduction, was 0.32 +/- 0.42 ml in saline-treated controls and 0.11 +/- 0.06 ml in Mg++-treated animals (difference 0.21 ml; p = 0.045). Serum Mg++ levels were significantly elevated in the Mg++-treated group. CONCLUSIONS: On the basis of their data, the authors suggest that CSDs play a minor role, if any, in the acute pathophysiology of SAH. Administration of Mg++ reduces the cerebral lesion volume that is present during the acute period after SAH. The neuroprotective value of Mg++ after SAH may, in part, be explained by a reduction in the duration of the ID of brain cells.

Animals↗
PubMed1997

Motions of calmodulin characterized using both Bragg and diffuse X-ray scattering.

BACKGROUND: Calmodulin is a calcium-activated regulatory protein which can bind to many different targets. The protein resembles a highly flexible dumbbell, and bends in the middle as it binds. This and other motions must be understood to formulate a realistic model of calmodulin function. RESULTS: Using the Bragg reflections from X-ray crystallography, a multiple-conformer refinement of a calmodulin-peptide complex shows anisotropic displacements, with high variations of dihedral angles in several nonhelical domains: the flexible linker; three of the four calcium-binding sites (including both of the N-terminal sites); and a turn connecting the C-terminal EF-hand calcium-binding domains. Three-dimensional maps of the large scale diffuse X-ray scattering data show isotropic liquid-like motions with an unusually small correlation length. Three-dimensional maps of the small scale diffuse streaks show highly coupled, anisotropic motions along the head-to-tail molecular packing direction in the unit cell. There is also weak coupling perpendicular to the head-to-tail packing direction, particularly across a cavity occupied by the disordered linker domain of the molecule. CONCLUSIONS: Together, the Bragg and diffuse scattering present a self-consistent description of the motions in the flexible linker of calmodulin. The other mobile regions of the protein are also of great interest. In particular, the high variations in the calcium-binding sites are likely to influence how strongly they bind ions. This is especially important in the N-terminal sites, which regulate the activity of the molecule.

Algorithms↗
PubMed1977

Supersaturation by counterperfusion and diffusion of gases.

Gaseous supersaturation can be induced under steady-state conditions when two inert gases are transmitted in opposite directions across any system comprising a diffusion barrier adjacent to a zone of limited convective capacity. This has many implications for bubble formation in vivo and can explain the occurence of symptoms of decompression sickness without decompression.

Decompression Sickness↗
PubMed1980

Motions of tropomyosin. Crystal as metaphor.

Movements of tropomyosin play an essential role in muscle regulation. This fibrous protein is a two-chain alpha-helical coiled coil that bonds head to tail to form cables wound in the two long grooves of the actin helix. The regulatory switch consists of tropomyosin and a "globular" Ca2+-sensitive protein complex called troponin. The structure of the tropomyosin filaments has now been determined by x-ray crystallography to approximately 15 A resolution. The complete sequence of alpha-tropomyosin is known; by using mercury markers on the cysteine residues the ends of the molecules in the filaments have been identified. Details of the coiled-coil structure have also been visualized by refinement of models against the diffraction data. The average pitch of the coiled coil is approximately 137 A, so that each tropomyosin molecule can make similar contacts with seven actin monomers. The electron density map also indicates that departures from the alpha-helical coiled coil occur in a few localized regions of the molecule, especially at the overlapping ends. Motions of tropomyosin in the crystal lattice are displaced by the character of the Bragg reflections and the strong diffuse scatter. These effects depend markedly on temperature. It appears that the molecular filaments fluctuate freely in a direction perpendicular to their axes. Moreover, the C-terminal half of the molecule "unfolds" to some degree at less than physiological temperatures. Crystallographic results on co-crystals of tropomyosin and a component of troponin (TnT) suggest that this subunit consists of structurally distinct domains, so that the troponin complex is not in fact simply "globular". The interactions of the extended alpha-helical region of TnT may "stiffen" tropomyosin and influence its motions. We picture the tropomyosin/troponin switch in muscle as a restless cable, perpetually making and breaking bonds as it vibrates on the thin filament. These movements of tropomyosin probably depend on two aspects of its design: the regular pattern of coiled-coil linkages with actin; and the aperiodic features that allow flexibility and motion.

Animals↗
PubMed1991

An effectiveness factor you can see. Experimental visualization of the effectiveness factor concept in a biological system.

Effectiveness factor values corresponding to carrageenan immobilized yeast beads packed in a continuous tubular fermenter are obtained from the mathematical modelization of the reactor performing ethanol fermentation. Simultaneously, microscopical direct observation of transversal sections corresponding to two different points in the fermenter is in good agreement with the calculated values: An effectiveness factor near to unity gives a uniform cell distribution in beads, as an effectiveness factor near to 0.75 corresponds to a non-uniform cell growth in beads. This observation gives a visual evidence of the validity of the approach used to treat diffusional limitations in biocatalytic particles.

Biotechnology↗
PubMed2003

Expression and release of CD14 in astrocytic brain tumors.

CD14 is a membrane-bound lipopolysaccharide receptor or, lacking the glycosylphosphatidylinositol anchor, is secreted to modulate cellular and humoral immune response by interacting directly with T and B cells. Because immunodepletion is thought to contribute to the grim prognosis of glioblastoma patients, we analyzed expression and release of CD14 in rat and human astrocytomas and glioma cell lines. Immunohistochemistry of 50 glioma biopsy specimens from low-grade diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV), and of the C6 rat glioma model demonstrated significantly more CD14-immunoreactive macrophages/microglial cells in glioblastomas than in less malignant gliomas. In WHO grade II and III astrocytomas, only perivascular cells showed immunoreactivity with CD14. In glioblastomas, CD14-immunoreactive cells were mainly found scattered throughout the entire tumor parenchyma. Double labeling experiments demonstrated CD14 immunoreactivity predominantly in CD68-expressing macrophages/microglial cells and some glioma cells. Western blotting, reverse transcription-PCR and consecutive sequencing confirmed expression and release of CD14 by four of six analyzed glioma cell lines. These results demonstrate that CD14 is expressed, and more importantly released, from a subset of human glioma cells and infiltrating macrophages/microglial cells that may contribute to immunodepletion observed in these patients.

Adult↗
PubMed2005

Body sway during quiet standing: is it the residual chattering of an intermittent stabilization process?

This paper reviews different approaches for explaining body sway while quiet standing that directly address the instability of the human inverted pendulum. We argue that both stiffness control [Winter, D. A., Patla, A. E., Riedtyk, S., & Ishac, M. (2001). Ankle muscle stiffness in the control of balance during quiet standing. Journal of Neurophysiology, 85, 2630-2633] and continuous feedback control by means of a PID (Proportional, Integral, Derivative) mechanism [Peterka, R. J. (2000). Postural control model interpretation of stabilogram diffusion analysis. Biological Cybernetics, 83, 335-343.] can guarantee asymptotic stability of controlled posture at the expense of unrealistic assumptions: the level of intrinsic muscle stiffness in the former case, and the level of background noise in the latter, which also determines an unrealistic level of jerkiness in the sway. We show that the decomposition of the control action into a slow and a fast component (rambling and trembling, respectively, as proposed by [Zatsiorsky, V. M., & Duarte, M. (1999). Instant equilibrium point and its migration in standing tasks: Rambling and trembling components of the stabilogram. Motor Control, 4, 185-200; Zatsiorsky, V. M., & Duarte, M. (2000). Rambling and trembling in quiet standing. Motor Control, 4, 185-200.]) is useful but must be modified in order to take into account that rambling is not a stable equilibrium trajectory. We address the possibility of a form of stability weaker than asymptotic stability in light of the intermittent stabilization mechanism outlined by [Loram, I. D., & Lakie, M. (2002a). Human balancing of an inverted pendulum: position control by small, ballistic-like, throw and catch movements. Journal of Physiology, 540, 1111-1124.], and propose an indicator of intermittent stabilization that is related to the phase portrait of the human inverted pendulum. This indicator provides a further argument against the plausibility of PID-like control mechanisms. Finally, we draw attention to the sliding mode control theory that provides a useful theoretical framework for formulating realistic intermittent, stabilization models.

Adult↗
PubMed2006

The GIS-based SafeAirView software for the concentration assessment of radioactive pollutants after an accidental release.

The European Commission Joint Research Centre (JRC) in Ispra (Italy) has long been running nuclear installations for research purposes. The Nuclear Decommissioning and Facilities Management Unit (NDFM) is responsible for the surveillance of radioactivity levels in nuclear emergency conditions. The NDFM Unit has commissioned the implementation of a specifically developed decision support system, which can be used for quick emergency evaluation in the case of hypothetical accident and for emergency exercises. The requisites were to be a user-friendly software, able to quickly calculate and display values of air and ground radioactive contamination in the complex area around JRC, following an accidental release of radioactive substances from a JRC nuclear research installation. The developed software, named "SafeAirView", is an advanced implementation of GIS technology applied to an existing MS-DOS mode dispersion model, SAFE_AIR (Simulation of Air pollution From Emissions_Above Inhomogeneous Regions). SAFE_AIR is a numerical model which simulates transport, diffusion, and deposition of airborne pollutants emitted in the low atmosphere above complex orography at both local and regional scale, under non-stationary and inhomogeneous emission and meteorological conditions. SafeAirView makes use of user-friendly MS-Windows type interface which drives the dispersion model by a sequential and continuous input-output process, allowing a real time simulation. The GIS environment allows a direct interaction with the territory elements in which the simulation takes place, using data for the JRC Ispra region represented in geo-referenced cartography. Furthermore it offers the possibility to relate concentrations with population distribution and other geo-referenced maps, in a geographic view. Output concentration and deposition patterns can be plotted and/or exported. In spite of the selected specific databases, the SafeAirView software architecture is a general structure, therefore the decision support system could be easily modified to be applied in a region different from the JRC one. Beside the description of SafeAirView, the present paper presents a statistical evaluation of the software, which has considered three well known tracer experiments: Copenhagen, Indianapolis and Kincaid. The data sets related to these experiments are all included in the so called Model Validation Kit.

Data Interpretation, Statistical↗
PubMed2024

Diffusion within the synaptonemal complex can account for signal transduction along meiotic chromosomes.

Meiotic chromosomes efficiently transduce information along their length to regulate the distribution of genetic exchanges (crossovers). However, the mode of signal transduction remains unknown. A conserved protein interface called the synaptonemal complex forms between the parental chromosomes. The synaptonemal complex exhibits liquid-like behaviors, suggesting that the diffusion of signaling molecules along its length could coordinate crossover formation. Here, we directly test the feasibility of such a mechanism by tracking a component of the synaptonemal complex (SYP-3) and a conserved regulator of exchanges (ZHP-3) in live Caenorhabditis elegans gonads. While we find that both proteins diffuse within the synaptonemal complex, ZHP-3 diffuses 4- and 9-fold faster than SYP-3 before and after crossover designation, respectively. We use these measurements to parameterize a physical model for signal transduction. We find that ZHP-3, but not SYP-3, can explore the lengths of chromosomes on the time scale of crossover designation, consistent with a role in the spatial regulation of exchanges. Given the conservation of ZHP-3 paralogues across eukaryotes, we propose that diffusion along the synaptonemal complex may be a conserved mechanism of meiotic regulation. More broadly, our work explores how diffusion compartmentalized by condensates could regulate crucial chromosomal functions.

Synaptonemal Complex↗
PubMed2000

Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur.

In vitro and in vivo skin absorption of the pesticide propoxur (2-isopropoxyphenyl N-methyl carbamate, commercially Baygon(TM) and Unden (TM); log Po/w 1.56, MW 209.2) was investigated. In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In vitro experiments were carried out in static diffusion cells using viable full-thickness skin membranes (rat and human), non-viable epidermal membranes (rat and human) and a perfused-pig-ear model. Percutaneous penetration of propoxur in human volunteers was measured by analysis of its metabolite (2-isopropoxyphenol) in blood and urine; in all other studies radiolabeled propoxur ([ring-U-(14)C]propoxur) was used. In order to allow for direct comparison, experimental conditions were standardized with respect to dose (150 microg propoxur per cm(2)), vehicle (60% aqueous ethanol) and exposure time (4 h). In human volunteers, it was found that approximately 6% of the applied dose was excreted via the urine after 24 h, while the potential absorbed dose (amount applied minus amount washed off) was 23 microg/cm(2). In rats these values were 21% and 88 microg/cm(2), respectively. Data obtained in vitro were almost always higher than those obtained in human volunteers. The most accurate in vitro prediction of the human in vivo percutaneous absorption of propoxur was obtained on the basis of the potential absorbed dose. The absorbed dose and the maximal flux in viable full-thickness skin membranes correlated reasonably well with the human in vivo situation (maximal overestimation by a factor of 3). Epidermal membranes overestimated the human in vivo data up to a factor of 8, but the species-differences observed in vivo were reflected correctly in this model. The data generated in the perfused-pig-ear model were generally intermediate between viable skin membranes and epidermal membranes.

Animal Testing Alternatives↗
PubMed1993

Pressure propagation in pulsatile flow through random microvascular networks.

A microvascular network with random dimensions of vessels is built on the basis of statistical analysis of conjunctival beds reported in the literature. Our objective is to develop a direct method of evaluating the statistics of the pulsatile hydrodynamic field starting from a priori statistics which mimic the large-scale heterogeneity of the network. The model consists of a symmetric diverging-converging dentritic network of ten levels of vessels, each level described by a truncated Gaussian distribution of vessel diameters and lengths. In each vascular segment, the pressure distribution is given by a diffusion equation with random parameters, while the blood flow rate depends linearly on the pressure gradient. The results are presented in terms of the mean value and standard deviation of the pressure and flow rate waveforms at two positions along the network. It is shown that the assumed statistical variation of vessel lengths results in flow rate deviations as high as 50 percent of the mean, while the corresponding effect of vessel diameter variation is much smaller. For a given pressure drop, the statistical variation of lengths increases the mean flow while the effect on the mean pressure distribution is negligible.

Blood Pressure↗
PubMed2005

The influence of finite cavities on the sound insulation of double-plate structures.

Lightweight walls are often designed as frameworks of studs with plates on each side--a double-plate structure. The studs constitute boundaries for the cavities, thereby both affecting the sound transmission directly by short-circuiting the plates, and indirectly by disturbing the sound field between the plates. The paper presents a deterministic prediction model for airborne sound insulation including both effects of the studs. A spatial transform technique is used, taking advantage of the periodicity. The acoustic field inside the cavities is expanded by means of cosine-series. The transmission coefficient (angle-dependent and diffuse) and transmission loss are studied. Numerical examples are presented and comparisons with measurement are performed. The result indicates that a reasonably good agreement between theory and measurement can be achieved.

Journal Article↗
PubMed2005

Subtle difference between benzene and toluene dioxygenases of Pseudomonas putida.

Benzene dioxygenase and toluene dioxygenase from Pseudomonas putida have similar catalytic properties, structures, and gene organizations, but they differ in substrate specificity, with toluene dioxygenase having higher activity toward alkylbenzenes. The catalytic iron-sulfur proteins of these enzymes consist of two dissimilar subunits, alpha and beta; the alpha subunit contains a [2Fe-2S] cluster involved in electron transfer, the catalytic nonheme iron center, and is also responsible for substrate specificity. The amino acid sequences of the alpha subunits of benzene and toluene dioxygenases differ at only 33 of 450 amino acids. Chimeric proteins and mutants of the benzene dioxygenase alpha subunit were constructed to determine which of these residues were primarily responsible for the change in specificity. The protein containing toluene dioxygenase C-terminal region residues 281 to 363 showed greater substrate preference for alkyl benzenes. In addition, we identified four amino acid substitutions in this region, I301V, T305S, I307L, and L309V, that particularly enhanced the preference for ethylbenzene. The positions of these amino acids in the alpha subunit structure were modeled by comparison with the crystal structure of naphthalene dioxygenase. They were not in the substrate-binding pocket but were adjacent to residues that lined the channel through which substrates were predicted to enter the active site. However, the quadruple mutant also showed a high uncoupled rate of electron transfer without product formation. Finally, the modified proteins showed altered patterns of products formed from toluene and ethylbenzene, including monohydroxylated side chains. We propose that these properties can be explained by a more facile diffusion of the substrate in and out of the substrate cavity.

Base Sequence↗
PubMed2006

Gliomas: histopathologic evaluation of changes in directionality and magnitude of water diffusion at diffusion-tensor MR imaging.

PURPOSE: To retrospectively correlate changes in fractional anisotropy (FA) and mean diffusivity in gliomas at diffusion-tensor magnetic resonance (MR) imaging with the degree of tumor cell infiltration determined histologically. MATERIALS AND METHODS: The institutional review board required neither ethics committee approval nor patient informed consent for this study. Twenty patients (eight women, 12 men; age range, 18-53 years) with glioma (seven World Health Organization grade II and 13 grade III tumors) underwent diffusion-tensor MR imaging at 1.5 T. Diffusion-tensor data were obtained with an echo-planar imaging sequence with six diffusion directions (b = 1000 sec/mm(2)), isotropic 1.9-mm voxels, and five averages. FA and mean diffusivity values were calculated from diffusion-tensor data. Coregistration with a three-dimensional MR imaging data set (used for stereotactic brain biopsies) enabled correlation of FA and mean diffusivity values with the histopathologic findings total cell number (CN), tumor CN, and percentage tumor infiltration (TI) by using linear, exponential, and logarithmic models. Student t and Mann-Whitney U tests were performed. RESULTS: Histopathologic findings of 77 MR image-guided stereotactic biopsies in all 20 patients were correlated with FA and mean diffusivity values at the biopsy locus. For FA and mean diffusivity, a logarithmic model showed strongest correlation with tumor CN and total CN; a linear model showed strongest correlation with percentage TI. For FA there were negative logarithmic (R = -0.802, P < .001) and linear (R = -0.796, P < .001) correlations with tumor CN and percentage TI, respectively. For mean diffusivity there were positive logarithmic (R = 0.557, P < .001) and linear correlations (R = 0.521, P < .001) with tumor CN and percentage TI, respectively. Differences between correlations for FA and mean diffusivity versus tumor CN (P < .001) and percentage TI (P < .001) were significant. CONCLUSION: FA is better than mean diffusivity for assessment and delineation of different degrees of pathologic changes (ie, TI) in glioma.

Adolescent↗
PubMed2006

Methods for investigating placental fatty acid transport.

Fatty acids (FAs), especially essential fatty acids (EFAs) and their long chain polyunsaturated fatty acid (LCPUFAs) derivatives, are critical for proper fetal development. The fetus relies on the placental transfer of EFAs from the maternal circulation for development. In fact, fatty acid transfer is highly directional from the mother to the fetus. Significant changes in placental fatty acid transport and metabolism, the two primary processes that govern placental FA supply from mother to fetus, can subsequently result in aberrant fetal fatty acid/lipid homeostasis and dramatically increase the risk of abnormal fetal development. Besides passive diffusion, specific fatty acid transfer conferring proteins can actively mediate directional placental fatty acid uptake and transport. Enzymes for fatty acid beta-oxidation and synthesis and the ones participating PUFA metabolism, including cytochrome P450 (mainly CYP4A), cyclooxygenases (COXs), and lipooxygenases (LOXs), have also been identified in the placenta. Methods for studying functional placental fatty acid uptake/transport/metabolism are discussed, focusing on an in vitro placental trophoblast model and long chain unsaturated fatty acids. The relevant theory of FA transport pathways, kinetic data analysis (uptake rates, permeability, influx/efflux ratio, Km, and so on) and high-performance liquid chromatography identification are also discussed.

Animals↗
PubMed1992

Nonionic diffusion of salicylic acid through MDCK cell monolayers.

MDCK-I cells, grown on collagen-coated filters, were used as a model of the distal nephron to study the nonionic diffusion of salicylic acid. The apparent transcellular permeability (PSal, centimeters per second) and intracellular content (ContSal, picomoles) of [14C]salicylic acid (ionized and nonionized) were measured from both apical-to-basolateral and basolateral-to-apical unidirectional fluxes. During the measurement of apical-to-basolateral fluxes at 21 degrees C, both PSal and ContSal correlated directly with the proportion of nonionized salicylic acid in the apical medium over the pH range 6.0-7.4. This indicated that the observed permeability was due to pure nonionic diffusion. However, in the basolateral-to-apical direction, the correlation was less evident and ContSal was 10 to 20 times higher, although PSal was of the same magnitude. These observations could not be explained by facilitated transport of anionic salicylic acid, at 21 degrees C, because 1 mM probenecid, 1 mM p-aminohippurate and 1 mM cold salicylic acid did not abolish the higher intracellular content obtained during basolateral-to-apical fluxes. Raising the temperature produced only a gradual increase of PSal measured in the basolateral-to-apical direction and an unexpected decrease of ContSal. Because basolateral-to-apical facilitated transport does not play a significant role, the most plausible reason for the higher ContSal during basolateral-to-apical fluxes is that the apical membrane possesses a much lower (10- to 20-fold less) salicylic acid permeability than the basolateral membrane and constitutes the rate-limiting step for transcellular salicylic acid flux.

Animals↗
PubMed1998

Ocular fixation index and mathematical models.

Ocular fixation test and ocular fixation index (OFI) never have been interpreted in terms of mathematical models, despite their widespread diffusion. However, ocular fixation is a typical case of visual-vestibular interaction, and mathematical models have proven very helpful in interpreting some mechanisms of this interaction, e.g. those of the optokinetic-vestibular interaction. In the present paper, a first attempt is proposed toward a model interpretation of OFI. By using very simple mathematical models, the hypothesis is tested that visual suppression of vestibular nystagmus results from direct action of smooth pursuit system (SPS). The aim is to draw consequences and recognize possible limits of this hypothesis. Dependence of OFI on SPS performance is examined. Although the available experimental data are insufficient for comprehensive validation of the model, the results agree with the current interpretations. In particular, quantitative support is given to the sensitivity of OFI to central vestibular diseases. Although the interpretation of visual suppression and OFI in terms of mathematical models is still at a very preliminary stage, models may provide a theoretical reference framework for the interpretation of new experimental results and/or suggest new test protocols.

Fixation, Ocular↗