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Asymmetric Distribution (asymmetric + distribution)
Selected AbstractsCaveolin-1 polarization in migrating endothelial cells is directed by substrate topology not chemoattractant gradientCYTOSKELETON, Issue 11 2006Virginie Santilman Abstract Polarization is a hallmark of migrating cells, and an asymmetric distribution of proteins is essential to the migration process. Caveolin-1 is highly polarized in migrating endothelial cells (EC). Several studies have shown caveolin-1 accumulation in the front of migrating EC while others report its accumulation in the EC rear. In this paper we address these conflicting results on polarized localization of caveolin-1. We find evidence for the hypothesis that different modes of locomotion lead to differences in protein polarization. In particular, we show that caveolin-1 is primarily localized in the rear of cells migrating on a planar substrate, but in the front of cells traversing a three-dimensional pore. We also show that a chemoattractant, present either as a gradient or ubiquitously in the medium, does not alter caveolin-1 localization in cells in either mode of locomotion. Thus we conclude that substrate topology, and not the presence of a chemoattractant, directs the polarization of caveolin-1 in motile ECs. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source] High-frequency stimuli preferentially release large dense-core vesicles located in the proximity of nonspecialized zones of the presynaptic membrane in sympathetic gangliaDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2008F. Cifuentes Abstract We characterized the effect of a brief high-frequency stimulus on the number, distribution, and optical density of large dense-core vesicles (LDCVs) in the nerve terminals of the rat superior cervical ganglia. From 4.21 ± 0.37 LDCVs/bouton detected in control nerve terminals, a stimulus of 40 Hz for 1 min released 41% of LDCVs, decreasing their number to 2.48 ± 0.14 LDCVs/bouton (p = 0.0009). In control ganglia, most dense vesicles were located close to the plasma membrane (at ,100 nm); in contrast, in stimulated ganglia they were broadly distributed with respect to the active zone. The mean distance of LDCVs to membrane and active zones was 95 ± 8 nm and 473 ± 15 nm, respectively. The analysis of the core density showed that both groups had a similar asymmetric distribution with the same average. Stimulation preferentially released those vesicles located ,100 nm from the plasma membrane that had no apparent relationship with the active zone. After the stimulus, the average distances of LDCVs to the plasma membrane and active zone did not change, suggesting that the stimulus also caused the relocation of inner LDCVs. Interestingly, optical density analysis showed that the released vesicles had low range densities, and suggested that LDCVs release their entire content. We conclude that LDCV exocytosis mainly involves those vesicles located ,100 nm from the plasma membrane and occurs in regions of synaptic boutons presumed to be nonspecialized. These results agree with the characteristics of the classical model that proposes full content release. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Use of Chronic Epilepsy Models in Antiepileptic Drug Discovery: The Effect of Topiramate on Spontaneous Motor Seizures in Rats with Kainate-induced EpilepsyEPILEPSIA, Issue 1 2005Heidi L. Grabenstatter Summary:,Purpose: Potential antiepileptic drugs (AEDs) are typically screened on acute seizures in normal animals, such as those induced in the maximal electroshock and pentylenetet-razole models. As a proof-of-principle test, the present experiments used spontaneous epileptic seizures in kainate-treated rats to examine the efficacy of topiramate (TPM) with a repeated-measures, crossover protocol. Methods: Kainic acid was administered in repeated low doses (5 mg/kg) every hour until each Sprague,Dawley rat experienced convulsive status epilepticus for >3 h. Six 1-month trials (n = 6,10 rats) assessed the effects of 0.3,100 mg/kg TPM on spontaneous seizures. Each trial involved six pairs of TPM and saline-control treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Data analysis included a log transformation to compensate for the asymmetric distribution of values and the heterogeneous variances, which appeared to arise from clustering of seizures. Results: A significant effect of TPM was observed for 12 h (i.e., two 6-h periods) after a 30-mg/kg injection, and full recovery from the drug effect was complete within 43 h. TPM exerted a significant effect at doses of 10, 30, and 100 mg/kg, and the effects of TPM (0.3,100 mg/kg) were dose dependent. Conclusions: These data suggest that animal models with spontaneous seizures, such as kainate- and pilocarpine-treated rats, can be used efficiently for rapid testing of AEDs with a repeated-measures, crossover protocol. Furthermore, the results indicate that this design allows both dose,effect and time-course-of-recovery studies. [source] Desmocollin 1 expression and desmosomal remodeling during terminal differentiation of human anagen hair follicle: an electron microscopic studyEXPERIMENTAL DERMATOLOGY, Issue 5 2004Elena Donetti Abstract:, The terminal differentiation (TD) program of keratinocytes of the human hair follicle (HF) occurs with specific temporal and spatial features in the various layers of the inner root sheath (IRS) and in the innermost layer of the outer root sheath (companion layer). This process is characterized by complex nuclear and cytoplasmic morphological changes, accompanied by profound modifications in intercellular junctions. As no correlation exists between the structure and the molecular composition of desmosomes during TD of the IRS/companion unit, the aim of our study was to investigate by transmission electron microscopy the remodeling of desmosomes in keratinizing cells of these compartments. By immunogold post embedding technique, we studied in anagen HFs the modulation of the synthesis of desmocollin 1 (Dsc1), a transmembrane glycoprotein specifically synthesized in the IRS and in the companion layer. Dsc1 immunoreactivity was actually confined to these compartments and tended to increase just before the level of TD, particularly in the Henle's layer and in the IRS cuticle. In Huxley's layer, the immunolabeling was patchy and in the companion layer Dsc1 synthesis was detected above the level of keratinization of Huxley's layer. In the whole IRS, concomitantly with TD, there was an abrupt and almost complete disappearance of Dsc1 synthesis. An asymmetric distribution of Dsc1 was noticed (i) between cells at different stages of differentiation and (ii) between cells belonging to layers with different spatial/temporal features of TD. Our results show that the ultrastructural modifications of desmosomes during TD of HF are paralleled by the modulation of the synthesis of desmocollin 1. [source] A discourse on cancer cell chemotaxis: Where to from here?IUBMB LIFE, Issue 2 2007Lilian L. Soon Abstract The study of cancer cell chemotaxis on two-dimensional surfaces in vitro has relevance to the diverse migratory behaviours exhibited in vivo that involve a directed path. These may include translocation along collagen fibres, invasion into the basement membrane and across stroma, intravasation and extravasation to arrive at a secondary destination designated for cancer cell colonization. Chemotaxis invariably denotes the ability of cells to sense gradients, polarize, adhere and deadhere to substrate, and translocate in the right direction. Amongst these, the sensing function is perhaps the unifying aspect of different migration styles, permitting the cells to resolve its orientation and path. This review examines the decision-making processes that take place during chemotaxis and illustrates that a universal mechanism is involved. In various cell types from Dictyostelium to neutrophils, there are some unifying principles that dictate sensing and how the putative leading edge and trailing end of cells are determined. Some of these principles have recently been applied in the study of cancer cell chemotaxis albeit different pathways are substituted. In amoeboid-like cancer cells, local excitation of the EGFR/PLC,/cofilin pathway and parallel, global inhibition of cofilin by LIMK occur to promote the asymmetric distribution and amplification of these internal signals in response to an external EGF gradient. IUBMB Life, 59: 60-67, 2007 [source] Dielectric study of equimolar acetaminophen,aspirin, acetaminophen,quinidine, and benzoic acid,progesterone molecular alloys in the glass and ultraviscous states and their relevance to solubility and stabilityJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2010G.P. Johari Abstract Equimolar mixtures of acetaminophen,aspirin, acetaminophen,quinidine, and benzoic acid,progesterone have been vitrified and dielectric properties of their glassy and ultraviscous alloys have been studied. For 20,K/min heating rate, their Tgs are 266, 330, and 263,K, respectively. The relaxation has an asymmetric distribution of times, and the distribution parameter increases with increase in temperature. The dielectric relaxation time varies with T according to the Vogel,Fulcher,Tammann equation, log10(,0),=,AVFT,+,[BVFT/(T,,,T0)], where AVFT, BVFT, and T0 are empirical constants. The equilibrium permittivity is highest for the aspirin,acetaminophen and lowest for the benzoic acid-progesterone alloy, indicating a substantial interpharmaceutical hydrogen bonding that makes the alloy more stable against crystallization than the pure components. The benzoic acid,progesterone alloy is thermodynamically the most nonideal. It showed cold crystallization on heating, which is attributed to its relatively greater magnitude of the JG relaxation in relation to its ,-relaxation. It is argued that the difference between the free energy of an alloy and the pure components would have an effect on the solubility. Studies of solution thermodynamics of a glassy molecular alloy may be useful for optimizing choice of components and composition to form molecular alloys and to impact drug delivery. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1358,1374, 2010 [source] Dielectric studies of molecular motions in amorphous solid and ultraviscous acetaminophenJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2005G.P. Johari Abstract The dielectric permittivity and loss spectra of glassy and ultraviscous states of acetaminophen have been measured over the frequency range 10 Hz,0.4 MHz. The relaxation spectra show an asymmetric distribution of times expressed in terms of the Kohlrausch exponent, ,, which remains constant at 0.79,±,0.02 over the 305,341 K range. The dielectric relaxation time increases on cooling according to the Vogel,Fulcher,Tammann equation. However, the values of the parameters are considerably different from the values deduced from earlier work by other researchers using the heat capacity of ultraviscous acetaminophen and relating it to its molecular mobility. The calorimetric glass softening temperature of 296 K obtained from differential scanning calorimetry is close to the value measured from dielectric relaxation. The equilibrium permittivity of ultraviscous acetaminophen decreases on heating like that of a normal dipolar liquid, as anticipated from the Curie law. But, its value decreases rapidly with time when it begins to crystallize. The equilibrium permittivity of this crystal phase is ,3.1 at 300 K and increases with temperature, which indicates a partial, orientational-disordering of its structure. The results show limitations of the procedures used in the modeling of the kinetics of molecular motions, that is, estimating physical stability, using thermodynamic considerations based on thermal analyses of the amorphous solid phase of acetaminophen. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2207,2223, 2005 [source] Parameters of drug antagonism: re-examination of two modes of functional competitive drug antagonism on intraocular musclesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2004Popat N. Patil There are two distinct kinetic functional pharmacological procedures by which the equilibrium affinity constant, KB, of a competitive reversible blocker is obtained. The classical method on an organ system requires the study of the parallel displacement of the agonist concentration-response curve in the presence of the blocker. In the second method, the agonist-evoked functional mechanical response is reduced to half by the blocker IC50 (the concentration required for 50% inhibition). In relation to these parameters the role of the ionization constant pKa and liposolubility log Pc or log D of blockers was examined. On the ciliary muscle from human eye, IC50/KB ratios for (±)-atropine, its quaternary analogue (±)-methylatropine, (-)-scopolamine, (±)-cyclopentolate, (-)-tropicamide, (±)-oxybutynin and pirenzepine were 15, 23, 4.4, 2.6, 1.66, 1.46 and 1.71, respectively. The ratios on the iris sphincter were comparable with those of ciliary muscle. When compared with large proportions of ionized molecules with water soluble properties of (±)-atropine and (±)-methylatropine, relatively high amounts of un-ionized and/or with greater partitioning of all other blockers in the lipoid barrier co-related well to low IC50/KB ratios, as predicted by the classical theory of competitive drug antagonism. It was hypothesized that due to receptor biophase access, the reduction of the mechanical response of the agonist by the highly ionized water-soluble antagonist at IC50 represented time-distorted "pseudo-equilibrium" estimation, where a higher concentration of the blocker was needed. On the other cholinergic effectors, like that of rat anococcygeus muscle or frog rectus abdominus muscle, IC50/KB ratios of respective blockers atropine or (+)-tubocurarine and hexamethonium were close to 1. Thus physicochemical properties, which affect the distribution coefficient log D and the tissue morphology (where asymmetric distribution of receptors may occur), appeared to be a critical factor in the analysis of the affinity parameters of the competitive reversible blocker. On the intraocular muscles, two functional pharmacological procedures for obtaining KB and IC50 values were not kinetically equivalent. [source] Nasal-temporal differences in cone-opponency in the near peripheral retinaOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 3 2009A. Panorgias Abstract The purpose of this study is to establish whether nasal-temporal differences in cone photoreceptor distributions are linked to differences in colour matching performance in the two hemi-fields. Perceived shifts in chromaticity were measured using an asymmetric matching paradigm. They were expressed in terms of hue rotations and relative saturation changes and also in terms of activation levels of L,M or S,(L+M) cone-opponent channels. Up to 19° eccentricity there was little difference in chromaticity shifts between nasal and temporal retina for either channel. For matches beyond 19° L,M activation is significantly lower in the nasal field and the S,(L+M) channel was equally activated in both fields. The data are consistent with the asymmetric distribution of L- and M-cones in the nasal and temporal retinae. [source] EXAMINING THE ASYMMETRIC BEHAVIOUR OF MACROECONOMIC AGGREGATES IN ASIAN ECONOMIESPACIFIC ECONOMIC REVIEW, Issue 5 2008Paresh Kumar Narayan Abstract., The goal of this paper is to test for asymmetric behaviour of macroeconomic aggregates for three Asian economies; namely, Malaysia, Hong Kong and Korea. Whether macroeconomic aggregates can be characterised as asymmetric has important implications for policy-making and econometric modelling including forecasting. We examine two forms of asymmetries; specifically deepness, which arises when a detrended time series contains an asymmetric distribution, and steepness, which arises when the first difference of a series contains an asymmetric distribution. Overall, our findings suggest that for all three countries, the bulk of the series display asymmetry behaviour. [source] Case of the hidden assumptionsBIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 1 2002Daniel E. Koshland Jr The Ogston "three point attachment" model to explain how proteins discriminate between d and l isomers was originally proposed to explain the asymmetric distribution of isotopes that passed through a symmetric intermediate. It has been a standard in textbooks and the literature until the recent finding of Mesecar and Koshland [6] that it could not explain data of isocitrate dehydrogenase and other enzymes and must be replaced by a "four location model." The hidden assumptions that are part of the Ogston model are seen to be an interesting feature of the scientific method that can both advance and hinder scientific progress. [source] Adherens junctions: new insight into assembly, modulation and functionBIOESSAYS, Issue 8 2002Ulrich Tepass Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1,3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.5 BioEssays 24:690,695, 2002. © 2002 Wiley Periodicals, Inc. [source] REVIEW: Evidence for asymmetric distribution of lower intestinal tract endometriosisBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2004Paolo Vercellini First page of article [source] Surface topology and structural integrity of the Theromyzon tessulatum (Annelida: Hirudinea: Glossiphoniidae) cocoonJOURNAL OF MORPHOLOGY, Issue 7 2008Jon'elle Coleman Abstract Cocoons secreted by the aquatic leech Theromyzon tessulatum comprise a tubular, membranous ovoid, sealed at each end by a glue-like substance, called an operculum. Scanning electron microscopy showed surface features of the T. tessulatum cocoon that included a circuitous bulge, cups that conformed to the shape of embryos, relief folds that radiated from opercula, and asymmetric distributions of protuberances on the upper aspect of the cocoon surface. The structural integrity of the T. tessulatum cocoon was assessed after exposure to a variety of denaturing conditions (e.g., extreme heat, detergents, acids). Although both the fibrous cocoon membrane and opercula were strikingly resilient, the membrane/operculum boundary appeared to be the weakest structural component of the cocoon, consistent with its functional role as an escape hatch for juvenile leeches. The operculum itself was more sensitive to denaturation than the cocoon membrane, and thus was probably the source of a major protein component isolated from the T. tessulatum cocoon (i.e., Tcp; Theromyzon cocoon protein). J. Morphol., 2008. © 2008 Wiley-Liss, Inc. [source] The total median in statistical quality controlAPPLIED STOCHASTIC MODELS IN BUSINESS AND INDUSTRY, Issue 4 2004Fernanda Figueiredo Abstract In industry, most of the process observations are assumed to come from a normal population, but usually we merely want to control the process mean value. It is thus sensible to find control statistics, which are ,robust' to monitor the process mean, giving the expected rate of false alarms whenever that mean is close to the target value, although not under a normal regime. Simulation studies for a few symmetric and asymmetric distributions allow us to suggest the total median as a robust median estimator. We shall here analyse such a robustness, as well as the robustness of the total median chart comparatively to the sample mean chart, whenever we want to control the mean value of a symmetric underlying parent. Some indication is also provided on the comparative out-of-control behaviour of the two charts. Copyright © 2004 John Wiley & Sons, Ltd. [source] | |||||||||||||