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An additional electrostatic interaction between adrenodoxin and P450c27 (CYP27A1) results in tighter binding than between adrenodoxin and p450scc (CYP11A1).

Mitochondrial cytochrome P450c27 (product of the CYP27A1 gene) is found to have significantly higher affinity for the common redox partner adrenodoxin than another mitochondrial P450, P450scc (product of the CYP11A1 gene). To investigate the basis of the approximately 30-fold difference in adrenodoxin binding, two sets of P450c27 mutants were generated, expressed in Escherichia coli, and purified. Mutations of one set were within the putative adrenodoxin-binding site containing conserved lysine residues also crucial in P450scc for binding adrenodoxin. The second set included mutations within a sequence aligning with the "meander region" of P450BM-3 proposed to be a site of redox-partner interactions in P450s (Hasemann, C. A., Kurumbail, R. G., Boddupalli, S. S., Peterson, J. A., and Deisenhofer, J. (1995) Structure 3, 41-62). Mutation of the P450c27 conserved lysines (K354A and K358A) led to a approximately 20-fold increase in apparent Ks for adrenodoxin, confirming that these two positively charged residues conserved in mitochondrial P450s are important for adrenodoxin binding. Mutation of Arg-418, conserved in the CYP27A1 family, to serine also decreased the affinity for adrenodoxin approximately 20-fold. This residue is predicted to be located in the meander region. A triple K354A/K358A/R418S mutation profoundly reduced adrenodoxin binding. Thus, in contrast to P450scc, where mutation of the two conserved positively charged residues results in virtually complete inhibition of adrenodoxin binding, in P450c27 there are three of such residues (Lys-354, Lys-358, and Arg-418) important for adrenodoxin interaction.

Adrenodoxin↗

From local to global spatiotemporal chaos in a cardiac tissue model.

Two kinds of chaos can occur in cardiac tissue, chaotic meander of a single intact spiral wave and chaotic spiral wave breakup. We studied these behaviors in a model of two-dimensional cardiac tissue based on the Luo-Rudy I action potential model. In the chaotic meander regime, chaos is spatially localized to the core of the spiral wave. When persistent spiral wave breakup occurs, there is a transition from local to global spatiotemporal chaos.

Action Potentials↗

Asymptotic step profiles from a nonlinear growth equation for vicinal surfaces

We study a recently proposed nonlinear evolution equation describing the collective step meander on a vicinal surface subject to the Bales-Zangwill growth instability [O. Pierre-Louis et al., Phys. Rev. Lett. 80, 4221 (1998)]. A careful numerical analysis shows that the dynamically selected step profile consists of sloped segments, given by an inverse error function and steepening as sqrt[t], which are matched to pieces of a stationary (time-independent) solution describing the maxima and minima. The effect of smoothening by step-edge diffusion is included heuristically, and a one-parameter family of evolution equations is introduced that contains relaxation by step-edge diffusion and by attachment-detachment as special cases. The question of the persistence of an initially imposed meander wavelength is investigated in relation to recent experiments.

Journal Article↗

Dynamics of spiral waves under the modulation of noise pulses.

This work aims at investigating the dynamics of spiral waves under the modulation of noise pulses. Both rigid rotating and meandering spirals are considered. The numerical simulations show that for meandering spirals there exists a minimal external radius of the tip trajectory at an optimal intensity when keeping the duration constant, or for an optimal duration when keeping the intensity constant. For rigid rotating spirals an interesting phenomenon is that the clockwise-counterclockwise transition of the trajectory occurs when we raise the duration of the noise pulse for a fixed intensity.

Journal Article↗

Preventing alternans-induced spiral wave breakup in cardiac tissue: an ion-channel-based approach.

The detailed processes involved in spiral wave breakup, believed to be one major mechanism by which tachycardia evolves into fibrillation, are still poorly understood. This has rendered difficult the proper design of an efficient and practical control stimulus protocol to eliminate such events. In order to gain new insights into the underlying electrophysiological and dynamical mechanisms of breakup, we applied linear perturbation theory to a steadily rotating spiral wave in two spatial dimensions. The tissue was composed of cells modeled using the Fenton-Karma equations whose parameters were chosen to emphasize alternans as a primary mechanism for breakup. Along with one meandering mode, not just one but several unstable alternans modes were found with differing growth rates, frequencies, and spatial structures. As the conductance of the fast inward current was increased, the instability of the modes increased, consistent with increased meandering and propensity for spiral breakup in simulations. We also explored a promising new approach, based on the theory, for the design of an energy efficient electrical stimulus protocol to control spiral wave breakup. The novelty lies in addressing the problem directly at the ion channel level and taking advantage of the inherent two dimensional nature of the rotating wave. With the help of the eigenmode method, we were able to calculate the exact timing and amplitude of the stimulus, and locate it optimally to maximize efficiency. The analysis led to a special-case example that demonstrated that a single, properly timed stimulus can have a global effect, suppressing all growing alternans modes over the entire tissue, thus inhibiting spiral wave breakup.

Animals↗

Stabilization of unstable rigid rotation of spiral waves in excitable media.

Depending on the parameters of two-dimensional excitable or oscillatory media rigidly rotating or meandering spiral waves are observed. The transition from rigid rotation to meandering motion occurs via a supercritical Hopf bifurcation. To stabilize rigid rotation in a parameter range beyond the Hopf bifurcation, we propose and successfully apply a proportional control algorithm as well as time delay autosynchronization. Both control methods are noninvasive. This allows for determination of the parameters of unstable rigid rotation of spiral waves either for a model or an experimental system. Using the Oregonator model for the light-sensitive Belousov-Zhabotinsky reaction as a representative example we show that quite naturally some latency time appears in the control loop, and propose an efficient method to overcome its destabilizing influence.

Journal Article↗

Regular and alternant spiral waves of contractile motion on rat ventricle cell cultures.

We demonstrate that meandering as well as regular spiral waves can form in a well-controlled culture layer of rat ventricle cells and that the meandering spiral wave, in particular, can generate an alternant rhythm. These observations are made possible by a newly developed, noninvasive phase contrast macro-optics that is simple but highly effective in visualizing the contractile motion of the populations of cardiac cells.

Animals↗

Spirals, chaos, and new mechanisms of wave propagation.

The chaos theory is based on the idea that phenomena that appear disordered and random may actually be produced by relatively simple deterministic mechanisms. The disordered (aperiodic) activation that characterizes a chaotic motion is reached through one of a few well-defined paths that are characteristic of nonlinear dynamical systems. Our group has been studying VF using computerized mapping techniques. We found that in electrically induced VF, reentrant wavefronts (spiral waves) are present both in the initial tachysystolic stage (resembling VT) and the later tremulous incoordination stage (true VF). The electrophysiological characteristics associated with the transition from VT to VF is compatible with the quasiperiodic route to chaos as described in the Ruelle-Takens theorem. We propose that specific restitution of action potential duration (APD) and conduction velocity properties can cause a spiral wave (the primary oscillator) to develop additional oscillatory modes that lead to spiral meander and breakup. When spiral waves begin to meander and are modulated by other oscillatory processes, the periodic activity is replaced by unstable quasiperiodic oscillation, which then undergoes transition to chaos, signaling the onset of VF. We conclude that VF is a form of deterministic chaos. The development of VF is compatible with quasiperiodic transition to chaos. These results indicate that both the prediction and the control of fibrillation are possible based on the chaos theory and with the advent of chaos control algorithms.

Animals↗

Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties.

Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5x10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by approximately 70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1:1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0+/-1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response. The full text of this article is available at http://www.circresaha.org.

Acetylcholine↗

Afterdepolarizations promote the transition from ventricular tachycardia to fibrillation in a three-dimensional model of cardiac tissue.

Recent experimental results regarding the action potential duration restitution curve have explained the transition from ventricular tachycardia (VT) to fibrillation (VF) in terms of spiral wave (SW) meandering and breakup. However, it remains unclear whether VF always has a steep restitution curve. The present study was designed to test the hypothesis that afterdepolarizations occur at excitable gaps during VF and affect the SW dynamics, even if the restitution curve is gentle. Homogeneous and isotropic 3-dimensional tissue was simulated with a LRd model. Because of the gentle restitution curve, it was not expected that SW instabilities would occur in this condition. In the tissue, a stationary SW reentry was initially observed; however, afterdepolarizations erupted from the excitable gap near the SW tip, and the SW then meandered widely. Following that, afterdepolarizations erupted far from the SW tip, resulting in SW breakup. In this manner, the wave dynamics degenerated into a chaotic state within a few seconds. Furthermore, not only triggered activity but also subthreshold afterdepolarizations were found to cause SW instabilities. These results suggest that afterdepolarizations may play an important role in the transition to VF and that the mechanism is independent of restitution properties.

Computer Simulation↗

A transmission electron microscopic study on sinusoidal cells of guinea pig liver, with special reference to the occurrence of a canalicular system and "pored domes" in the endothelium.

Hepatic sinusoidal cells in the guinea pig were examined by transmission electron microscopy (TEM). A meandering canalicular system was detected in the sinusoidal endothelial cell both in thicker portions of cytoplasmic extensions and in small areas of the perikaryon. It consisted of meandering canaliculi with vacuolar expansions and constrictions, which penetrated the endothelial cytoplasm, forming as a whole a network. The canaliculi possessed more than two openings which usually communicated with the sinusoid, but occasionally poured themselves into the Disse's space. This network of canaliculi seems to permit infiltration of blood plasma. The "pored domes" recorded by Fujita and his collaborators on the glomerular endothelium of the rat and rabbit kidney were also revealed on the perikaryonal cytoplasm of the sinusoidal endothelium of guinea pig liver. Osmium-blackened lipid droplets were found in the sinusoidal endothelium, which suggested the release of lipid into the sinusoid. Short-term administrations of excessive vitamin A exerted no influence on the endothelial lipid droplets. The guinea pig is a rodent species which stores a very small amount of lipid droplets in its fat-storing cells and the so-called empty fat-storing cells were frequently detected. A single cilium was often found in the fat-storing cells in the guinea pig as in other species.

Animals↗

Nitrate removal in a riparian wetland of the Appalachian Valley and Ridge physiographic province.

Riparian zones within the Appalachian Valley and Ridge physiographic province are often characterized by localized variability in soil moisture and organic carbon content, as well as variability in the distribution of soils formed from alluvial and colluvial processes. These sources of variability may significantly influence denitrification rates. This investigation studied the attenuation of nitrate (NO3- -N) as wastewater effluent flowed through the shallow ground water of a forested headwater riparian zone within the Appalachian Valley and Ridge physiographic province. Ground water flow and NO3- -N measurements indicated that NO3- -N discharged to the riparian zone preferentially flowed through the A and B horizons of depressional wetlands located in relic meander scars, with NO3- -N decreasing from > 12 to < 0.5 mg L(-1). Denitrification enzyme activity (DEA) attributable to riparian zone location, soil horizon, and NO3- -N amendments was also determined. Mean DEA in saturated soils attained values as high as 210 microg N kg(-1) h(-1), and was significantly higher than in unsaturated soils, regardless of horizon (p < 0.001). Denitrification enzyme activity in the shallow A horizon of wetland soils was significantly higher (p < 0.001) than in deeper soils. Significant stimulation of DEA (p = 0.027) by N03- -N amendments occurred only in the meander scar soils receiving low NO3- -N (<3.6 mg L(-1)) concentrations. Significant denitrification of high NO3- -N ground water can occur in riparian wetland soils, but DEA is dependent upon localized differences in the degree of soil saturation and organic carbon content.

Carbon↗

Influence of geomorphological variability in channel characteristics on sediment denitrification in agricultural streams.

Within fluvial systems, the spatial variability of geomorphological characteristics of stream channels and associated streambed properties can affect many biogeochemical processes. In agricultural streams of the midwestern USA, it is not known how geomorphological variability affects sediment denitrification rates, a potentially important loss mechanism for N. Sediment denitrification was measured at channelized and meandering headwater reaches in east-central Illinois, a region dominated by intensive agriculture and high NO(3)-N stream export, between June 2003 and February 2005 using the chloramphenicol-amended acetylene inhibition procedure. Sediment denitrification rates were greatest in separation zones, ranging from 0.6 to 76.4 mg N m(-2) h(-1), compared with riffles, point bars, pools, and a run ranging from 0 to 36.5 mg N m(-2) h(-1). Differences in benthic organic matter (r = 0.70) and the percentage of fine-grained sediments (r = 0.93) in the streambeds controlled much of the spatial variations in sediment denitrification among the geomorphological features. Although two meandering study reaches removed 390 and 99% more NO(3)-N by sediment denitrification than adjacent channelized reaches, NO(3)-N loss rates from all reaches were between 0.1 and 15.7% d(-1), except in late summer. Regardless of geomorphological characteristics, streams in east-central Illinois were not able to process the high NO(3)-N loads, making sediment denitrification in this region a limited sink for N.

Agriculture↗

How does the ecological foraging behavior of desert kangaroo rats (Dipodomys deserti) relate to their behavior on radial mazes?

Experiment 1 showed that laboratory-reared desert kangaroo rats, like domestic Norway rats, efficiently search for food on a radial arm maze (RAM) by avoiding revisiting arms within a trial. By placing an RAM on the floor so the animals could approach food from any direction, Experiment 2 tested whether efficient search by kangaroo rats was based on tactics of distance minimizing, central-place foraging, trail following, or meandering. In contrast to the dominant trail-following tactic of domestic Norway rats (Hoffman, Timberlake, Leffel, & Gont, 1999), kangaroo rats tended to distance minimize, whether maze arms were present or not. Experiment 3 indicated that kangaroo rats treated a floor configuration of eight food cups as two patches of four, based on beeline travel between patches and meandering within them. We conclude that similar performance in an elevated RAM by different species can be based on different tactics, and we suggest that a laboratory apparatus can be used to cast light on niche-related mechanisms.

Animals↗

[Observations on Demodex folliculorum by scanning electron microscopy].

Additional observations on some fine structures of Demodex folliculorum under SEM were presented in this paper, including supracoxal spines, hypostome, palpal claws, male and female podosomal setae, leg claw-basal spur, femoral spur, etc. The supracoxal spines were rivet-shaped and the hypostome was pearshaped. The claws on the tarsal coxa of the pulpus meander to the ventral side instead of meandering to the dorsal side. Based on these structural characteristics, it was inferred that podosomal seta may be a sensilla and claw-basal spur as well as femoral spur can protect mites against being expelled from follicules.

Animals↗

Collateral mesenteric circulation.

The origins of historical terms, such as "Arc of Riolan" and "marginal artery of Drummond" are traced herein with emphasis on the inherent confusion caused when these terms are used. Basic mesenteric anatomy is briefly mentioned and pathologic anatomy with its altered direction of blood flow induced by atherosclerosis is stressed. The significance of the meandering mesenteric artery as the main collateral vessel between the superior and inferior mesenteric artery is emphasized along with preoperative and intraoperative ways to ascertain whether or not the origin of this latter vessel can be safely ligated. Specific operations, such as abdominal aortic aneurysmorrhaphy and sigmoid colectomy, which can potentially interfere with blood flow in the meandering mesenteric artery, are discussed in an attempt to prevent postoperative necrosis of any portion of the intestine that may have deficient mesenteric blood flow.

Blood Vessel Prosthesis↗

Glial fibrillary acidic protein-like immunoreactivity in the iris: development, distribution, and reactive changes following transplantation.

Using immunohistochemistry with antisera raised against the glial fibrillary acidic protein (GFA), we have studied the appearance and distribution of GFA-like immunoreactivity in whole mounts of rodent iris and in sectioned cat and cow iris. In the adult rat iris, a dense plexus of GFA-positive fibers was seen in both the dilator plate and the sphincter. The fluorescent fibers formed large meandering bundles and a dense irregular network of thinner fibers. In the sphincter, mainly thinner fibers were seen. Thin fibers were also seen winding around blood vessels in the dilator plate. In adult mouse iris, the GFA-positive fibers had a quite different distribution with a few radially oriented fiber bundles superimposed on a more regular network of thinner fibers. Adult guinea pig irides showed still another pattern of GFA-positive fibers with a low number of bundles and thinner fibers forming a sparse irregular network. In thicker fiber bundles of all three rodent species, as well as at branching sites of the thinner fibers, negative or weakly fluorescent swellings surrounded by GFA-like immunoreactivity were present. These structures probably represent the cellular origin of the GFA-positive fibers. Thick, strongly fluorescent fiber bundles, as well as numerous thinner fibers, were seen in sections of cat and cow iris. Prenatally, fibers were visualized at embryonic day 18 in the rat. In these irides as well as in irides from 21-day-old embryos and 1-day-old pups, most fibers were organized in a gradually increasing system of thin meandering fiber bundles that showed limited branching. At postnatal day 6, a more mature network of thinner fibers had developed between the now more numerous fiber bundles. No obvious increase or decrease in the amount of GFA-positive fibers was seen in irides grafted to the anterior eye chamber of adult rat recipients examined 1 and 6 days after grafting. However, in these irides, as well as in the host irides, strongly fluorescent spider-like cells with short branching processes and a negative nucleus were seen. These cells were more numerous and more strongly fluorescent in grafted irides as compared to recipient irides and in the 6-day iris grafts as compared to the 2-day grafts. In all probability, the GFA-positive fibers and cells forming a network in adult irides from different species and in embryonic and grafted rat irides represent Schwann cells and their processes. The cellular origin of the spider-like cells in the iris grafts is less clear.

Animals↗

[Studies on inferior mesenteric arterial stump blood pressure and aortographic findings in surgical cases of abdominal aortic aneurysm: in relation to ischemic colitis].

In 18 cases with unruptured abdominal aortic aneurysm, preoperative aortographic findings and the mean ratio of inferior mesenteric arterial stump blood pressure to systemic blood pressure (IMA/Syst. Pr. Ratio) were analyzed. In all cases IMA was ligated at operation because IMA/Syst. Pr. Ratio was more than 0.4, and one developed ischemic colitis. Preoperative aortogram was useful to identify meandering mesenteric artery and its flow direction to predict colon ischemia. IMA/Syst. Pr. Ratio following aortic reconstruction ranged from 0.41 to 1.0 with mean value of 0.70. In a case of ischemic colitis the ratio was the lowest value (0.5) except one case. Thus the ratio had diagnostic value to predict colon ischemia. Aortogram and IMA/Syst. Pr. Ratio were summed up to evaluate collateral circulation to colonic blood supply. Hypogastric arteries played an important role in some cases with intact IMA, and meandering mesenteric artery frequently in cases with occluded IMA. Consequently, it is important to preserve hypogastric arterial blood flow especially in the cases with intact IMA. In two cases whose internal iliac arteries were ligated bilaterally, IMA stump pressure was enough, and ischemic colitis was not encountered. The problems of peripheral vascular reconstruction in these two cases were also discussed.

Adult↗