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Insensitive
Selected AbstractsA Gonadotropin-Releasing Hormone Insensitive, Thapsigargin-Sensitive Ca2+ Store Reduces Basal Gonadotropin Exocytosis and Gene Expression: Comparison with Agonist-Sensitive Ca2+ StoresJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2003J. D. Johnson Abstract We examined whether distinct Ca2+ stores differentially control basal and gonadotropin (GTH-II)-releasing hormone (GnRH)-evoked GTH-II release, long-term GTH-II secretion and contents, and GTH-II- , mRNA expression in goldfish. Thapsigargin (Tg)-sensitive Ca2+ stores mediated neither caffeine-evoked GTH-II release, nor salmon (s)GnRH- and chicken (c)GnRH-II-stimulated secretion; the latter responses were previously shown to involve ryanodine (Ry)-sensitive Ca2+ stores. Surprisingly, Tg decreased basal GTH-II release. This response was attenuated by prior exposure to sGnRH and caffeine, but was insensitive to the phosphatase inhibitor okadaic acid, the inhibitor of constitutive release brefeldin A and cGnRH-II. GTH-II- , mRNA expression was decreased at 24 h by 2 µm Tg, and by inhibiting (10 µm Ry) and stimulating (1 nm Ry) Ry receptors. Transient increases in GTH-II- , mRNA were observed at 2 h and 12 h following 10 µm and 1 nm Ry treatment, respectively. Effects of Tg, Ry and GnRH on long-term GTH-II secretion, contents and apparent production differed from one another, and these changes were not well correlated with changes in GTH-II- , mRNA expression. Our data show that GTH-II secretion, storage and transcription can be independently controlled by distinct Ca2+ stores. [source] Mitochondrial S -Adenosyl- l -Methionine Transport is Insensitive to Alcohol-Mediated Changes in Membrane DynamicsALCOHOLISM, Issue 7 2009Anna Fernández Background:, Alcohol-induced liver injury is associated with decreased S -adenosyl- l -methionine (SAM)/S -adenosyl- l -homocysteine (SAH) ratio and mitochondrial glutathione (mGSH) depletion, which has been shown to sensitize hepatocytes to tumor necrosis factor (TNF). Aims:, As the effect of alcohol on mitochondrial SAM (mSAM) has been poorly characterized, our aim was to examine the status and transport of mSAM in relation to that of mGSH during alcohol intake. Methods:, Sprague,Dawley rats were pair fed Lieber,DeCarli diets containing alcohol for 1 to 4 weeks and liver fractionated into cytosol and mitochondria to examine the mSAM transport and its sensitivity to membrane dynamics. Results:, We found that cytosol SAM was depleted from the first week of alcohol feeding, with mSAM levels paralleling these changes. Cytosol SAH, however, increased during the first 3 weeks of alcohol intake, whereas its mitochondrial levels remained unchanged. mGSH depletion occurred by 3 to 4 weeks of alcohol intake due to cholesterol-mediated impaired transport from the cytosol. In contrast to this outcome, the transport of SAM into hepatic mitochondria was unaffected by alcohol intake and resistant to cholesterol-mediated perturbations in membrane dynamics; furthermore cytosolic SAH accumulation in primary hepatocytes by SAH hydrolase inhibition reproduced the mSAM depletion by alcohol due to the competition of SAH with SAM for mitochondrial transport. However, alcohol feeding did not potentiate the sensitivity to inhibition by SAH accumulation. Conclusions:, Alcohol-induced mSAM depletion precedes that of mGSH and occurs independently of alcohol-mediated perturbations in membrane dynamics, disproving an inherent defect in the mSAM transport by alcohol. These findings suggest that the early mSAM depletion may contribute to the alterations of mitochondrial membrane dynamics and the subsequent mGSH down-regulation induced by alcohol feeding. [source] Alcohol-Induced Tolerance and Physical Dependence in Mice With Ethanol Insensitive ,1 GABAA ReceptorsALCOHOLISM, Issue 2 2009David F. Werner Background:, Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, ,-aminobutyric acid type A receptors (GABAA -Rs) have been extensively implicated in ethanol action. The ,1 GABAA -R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that ,1-GABAA -Rs mediate in part these effects of ethanol. Methods:, Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin (KI) mice that have ethanol-insensitive ,1 GABAA -Rs and wildtype (WT) controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex (LORR) assays. Chronic tolerance was assessed on the LORR, fixed speed rotarod, hypothermia, and radiant tail-flick assays following 10 consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess ,1 protein levels. Results:, Compared with controls, KI mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between WT and KI mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in ,1 protein levels, but KIs did not. Conclusions:, We conclude that ,1-GABAA -Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on ,1-containing GABAA -Rs. [source] A High-Active Oxygen Electroreduction Catalyst Insensitive to the Presence of Methanol.CHEMINFORM, Issue 13 2003Keijiro Sawai Abstract For Abstract see ChemInform Abstract in Full Text. [source] Barycentric Coordinates on SurfacesCOMPUTER GRAPHICS FORUM, Issue 5 2010Raif M. Rustamov This paper introduces a method for defining and efficiently computing barycentric coordinates with respect to polygons on general surfaces. Our construction is geared towards injective polygons (polygons that can be enclosed in a metric ball of an appropriate size) and is based on replacing the linear precision property of planar coordinates by a requirement in terms of center of mass, and generalizing this requirement to the surface setting. We show that the resulting surface barycentric coordinates can be computed using planar barycentric coordinates with respect to a polygon in the tangent plane. We prove theoretically that the surface coordinates properly generalize the planar coordinates and carry some of their useful properties such as unique reconstruction of a point given its coordinates, uniqueness for triangles, edge linearity, similarity invariance, and smoothness; in addition, these coordinates are insensitive to isometric deformations and can be used to reconstruct isometries. We show empirically that surface coordinates are shape-aware with consistent gross behavior across different surfaces, are well-behaved for different polygon types/locations on variety of surface forms, and that they are fast to compute. Finally, we demonstrate effectiveness of surface coordinates for interpolation, decal mapping, and correspondence refinement. [source] Reference-Free Damage Classification Based on Cluster AnalysisCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 5 2008Hoon Sohn The ultimate goal of this study was to develop an in-site non-destructive testing (NDT) technique that can continuously and autonomously inspect the bonding condition between a carbon FRP (CFRP) layer and a host reinforced concrete (RC) structure, when the CRFP layer is used for strengthening the RC structure. The uniqueness of this reference-free NDT is two-fold: First, features, which are sensitive to CFRP debonding but insensitive to operational and environmental variations of the structure, have been extracted only from current data without direct comparison with previously obtained baseline data. Second, damage classification is performed instantaneously without relying on predetermined decision boundaries. The extraction of the reference-free features is accomplished based on the concept of time reversal acoustics, and the instantaneous decision-making is achieved using cluster analysis. Monotonic and fatigue load tests of large-scale CFRP-strengthened RC beams are conducted to demonstrate the potential of the proposed reference-free debonding monitoring technique. Based on the experimental studies, it has been shown that the proposed reference-free NDT technique may minimize false alarms of debonding and unnecessary data interpretation by end users. [source] Numerical Model for Biaxial Earthquake Response of Reinforced ConcreteCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 4 2007Cemalettin Dönmez The model is tested using data from two types of experiments with reinforced concrete elements: (1) elements subjected to varying pseudo-static biaxial lateral loads and (2) elements that responded biaxially to simulated earthquake motions. The goal for the model was not only to help determine the absolute maxima for earthquake response but also to enable calculation of the entire waveform, including the ranges of low- and moderate-amplitude response. The comparisons of measured and calculated results and sensitivity of the proposed model to variations in the input parameters are discussed. The output was found to be insensitive to the changes in input parameters related to concrete and sensitive to input parameters related to reinforcing steel. The results of the calculations were tested using experimental data. [source] Global simulation of a Czochralski furnace for silicon crystal growth against the assumed thermophysical propertiesCRYSTAL RESEARCH AND TECHNOLOGY, Issue 7 2006Y. R. Li Abstract In order to understand the effects of the thermophysical properties of the melt on the transport phenomena in the Czochralski (Cz) furnace for the single crystal growth of silicon, a set of global analyses of momentum, heat and mass transfer in small Cz furnace (crucible diameter: 7.2 cm, crystal diameter: 3.5 cm, operated in a 10 Torr argon flow environment) was carried out using the finite-element method. The global analysis assumed a pseudosteady axisymmetric state with laminar flow. The results show that different thermophysical properties will bring different variations of the heater power, the deflection of the melt/crystal interface, the axial temperature gradient in the crystal on the center of the melt/crystal interface and the average oxygen concentration along the melt/crystal interface. The application of the axial magnetic field is insensitive to this effect. This analysis reveals the importance of the determination of the thermophysical property in numerical simulation. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Cell hydration and mTOR-dependent signallingACTA PHYSIOLOGICA, Issue 1-2 2006F. Schliess Abstract Insulin- and amino acid-induced signalling by the mammalian target of rapamycin (mTOR) involves hyperphosphorylation of the p70 ribosomal S6 protein kinase (p70S6-kinase) and the eukaryotic initiation factor 4E (eIF4E) binding protein 4E-BP1 and contributes to regulation of protein metabolism. This review considers the impact of cell hydration on mTOR-dependent signalling. Although hypoosmotic hepatocyte swelling in some instances activates p70S6-kinase, the hypoosmolarity-induced proteolysis inhibition in perfused rat liver is insensitive to mTOR inhibition by rapamycin. Likewise, swelling-dependent proteolysis inhibition by insulin and swelling-independent proteolysis inhibition by leucine, a potent activator of p70S6-kinase and 4E-BP1 hyperphosphorylation, in perfused rat liver is insensitive to rapamycin, indicating that at least rapamycin-sensitive mTOR signalling is not involved. Hyperosmotic dehydration in different cell types produces inactivation of signalling components around mTOR, thereby attenuating insulin-induced glucose uptake, glycogen synthesis, and lipogenesis in adipocytes, and MAP-kinase phosphatase MKP-1 expression in hepatoma cells. Direct inactivation of mTOR, stimulation of the AMP-activated protein kinase, and the destabilization of individual proteins may impair mTOR signalling under dehydrating conditions. Further investigation of the crosstalk between the mTOR pathway(s) and hyperosmotic signalling will improve our understanding about the contribution of cell hydration changes in health and disease and will provide further rationale for fluid therapy of insulin-resistant states. [source] Assessment of myosin II, Va, VI and VIIa loss of function on endocytosis and endocytic vesicle motility in bone marrow-derived dendritic cellsCYTOSKELETON, Issue 10 2007Jeffrey P. Holt Abstract An essential feature of dendritic cell immune surveillance is endocytic sampling of the environment for non-self antigens primarily via macropinocytosis and phagocytosis. The role of several members of the myosin family of actin based molecular motors in dendritic cell endocytosis and endocytic vesicle movement was assessed through analysis of dendritic cells derived from mice with functionally null myosin mutations. These include the dilute (myosin Va), Snell's waltzer (myosin VI) and shaker-1 (myosin VIIa) mouse lines. Non muscle myosin II function was assessed by treatment with the inhibitor, blebbistatin. Flow cytometric analysis of dextran uptake by dendritic cells revealed that macropinocytosis was enhanced in Snell's waltzer dendritic cells while shaker-1 and blebbistatin-treated cells were comparable to controls. Comparison of fluid phase uptake using pH insensitive versus pH sensitive fluorescent dextrans revealed that in dilute cells rates of uptake were normal but endosomal acidification was accelerated. Phagocytosis, as quantified by uptake of E. coli, was normal in dilute while dendritic cells from Snell's waltzer, shaker-1 and blebbistatin treated cells exhibited decreased uptake. Microtubule mediated movements of dextran-or transferrin-tagged endocytic vesicles were significantly faster in dendritic cells lacking myosin Va. Loss of myosin II, VI or VIIa function had no significant effects on ratesof endocytic vesicle movement. Cell Motil. Cytoskeleton 2007. © 2007 Wiley-Liss, Inc. [source] Play fighting in androgen-insensitive tfm rats: Evidence that androgen receptors are necessary for the development of adult playful attack and defenseDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2006Evelyn F. Field Abstract The frequency of playful attack and the style of playful defense, are modifiable by gonadal steroids and change after puberty in male and female rats. The present study examined the play behavior exhibited by testicular feminized mutation (tfm) -affected males, who are insensitive to androgens but can bind estrogens aromatized from androgens, to determine the relative contributions of androgens and estrogens to the age-related changes in play behavior. tfm males did not exhibit a decrease in playful attack with age and were more likely to maintain the use of complete rotations, a juvenile form of playful defense, into adulthood. tfm males did however, show age related changes in the use of partial rotations and upright postures, two other forms of playful defense, that were similar to normal males. These data suggest that the development of play fighting and defense in males is dependent on both androgen- and estrogen-receptor-mediated effects. © 2006 Wiley Periodicals, Inc. Dev Psyshobiol 48: 111,120, 2006. [source] The underutilization of street markets as a source of food security indicators in Famine Early Warning Systems: a case study of EthiopiaDISASTERS, Issue 3 2008Michèle Companion Famine Early Warning Systems (EWS) are reliant on data aggregated from multiple sources. Consequently, they are often insensitive to localized changes in food security status, leading to delayed response or interventions. While price and infrastructural data are often gathered, this case study suggests that local street markets and vendor knowledge are underutilized. Few efforts have been made to monitor systematically the street markets as an indicator of local stressors. Findings from Ethiopia show that knowledge generated by expanding food security indicators in this sector can be used in combination with EWS to facilitate earlier intervention in, or to monitor more effectively, on-going humanitarian crises. Indicators developed from this study are accurate, cost effective, and sensitive to local climatic and food stressors. [source] Utility of esophageal biopsy in the diagnosis of nonerosive reflux diseaseDISEASES OF THE ESOPHAGUS, Issue 3 2003R. I. Narayani SUMMARY This study evaluated the accuracy of esophageal biopsy for the diagnosis of nonerosive reflux disease (NERD) in adults. Thirty-five patients with reflux symptoms and a normal endoscopy were prospectively evaluated using esophageal biopsies, 24-h ambulatory pH monitoring and symptomatic response 4 weeks after an increase in antireflux therapy. Biopsies were scored for the total number of typical histologic reflux features seen. Patients were considered to have NERD if both pH-metry was positive and step-up therapy was successful. Biopsies were then compared to this predefined gold standard. Biopsy was most sensitive (62%) but poorly specific (27%) when one or more histologic reflux features were seen. A threshold of three or more histologic features improved the specificity (91%) but reduced sensitivity (31%). Response to step-up therapy was associated with 100% sensitivity and 100% negative predictive value when compared to biopsy and pH-metry as an alternate combined gold standard. In conclusion, biopsy is insensitive in diagnosing NERD but reasonably specific if three or more typical histologic reflux features are present. [source] Pounding of structures modelled as non-linear impacts of two oscillatorsEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 5 2001K. T. Chau Abstract A new formulation is proposed to model pounding between two adjacent structures, with natural periods T1 and T2 and damping ratios ,1 and ,2 under harmonic earthquake excitation, as non-linear Hertzian impact between two single-degree-of-freedom oscillators. For the case of rigid impacts, a special case of our analytical solution has been given by Davis (,Pounding of buildings modelled by an impact oscillator' Earthquake Engineering and Structural Dynamics, 1992; 21:253,274) for an oscillator pounding on a stationary barrier. Our analytical predictions for rigid impacts agree qualitatively with our numerical simulations for non-rigid impacts. When the difference in natural periods between the two oscillators increases, the impact velocity also increases drastically. The impact velocity spectrum is, however, relatively insensitive to the standoff distance. The maximum relative impact velocity of the coupled system can occur at an excitation period Tn* which is either between those of the two oscillators or less than both of them, depending on the ratios T1/T2 and ,1/,2. Although the pounding force between two oscillators has been primarily modelled by the Hertz contact law, parametric studies show that the maximum relative impact velocity is not very sensitive to changes in the contact parameters. Copyright © 2001 John Wiley & Sons, Ltd. [source] Regional Response of Myocardial Acceleration During Isovolumic Contraction During Dobutamine Stress Echocardiography: A Color Tissue Doppler Study and Comparison with Angiocardiographic FindingsECHOCARDIOGRAPHY, Issue 10 2005Linda B. Pauliks M.D. Background: Color tissue Doppler imaging permits noninvasive quantitation of regional wall motion. In experimental studies, a new marker, the slope of the isovolumic contraction wave, isovolumic acceleration (IVA) was more insensitive to ventricular loading conditions than myocardial velocities. This study compared the regional response IVA to dobutamine stress echocardiography to angiographic findings. Methods: The Myocardial Doppler in Stress Echocardiography (MYDISE) study prospectively recruited 149 consecutive patients with chest pain for dobutamine stress tissue Doppler echocardiography prior to coronary angiography. This color tissue Doppler database was analyzed for IVA in 1192 basal and mid segments at rest and again at peak stress. Angiographic findings were compared to IVA and peak systolic velocities (PSV) in corresponding cardiac segments. The diagnostic accuracy of IVA to predict coronary artery stenosis was determined using cut-off values for three representative segments and with the MYDISE diagnostic model including eight segments. Results: Regional IVA increased in a dose-dependent manner during dobutamine infusion. The response was blunted in the supply territory of stenosed coronary artery branches. IVA performed slightly better than PSV as single marker for coronary artery stenosis. A diagnostic model incorporating IVA and PSV was 85,95% accurate (area under receiver operating characterstic curves). Conclusions: Regional changes of isovolumic acceleration during dobutamine stress echocardiography reflect regional wall motion and can be used to predict coronary artery stenosis with similar accuracy as a model based on systolic myocardial velocities. As a single marker, IVA performed better than myocardial velocities. (ECHOCARDIOGRAPHY, Volume 22, November 2005) [source] In Vitro Validation of a New Approach for Quantitating Regurgitations Using Proximal Isovelocity Surface AreaECHOCARDIOGRAPHY, Issue 7 2000A. Delouche The present work has been designed to validate the calculation of the effective regurgitant orifice (ERO) area with the use of a new formula that takes into account the velocity profile (Vr vs r) and that is insensitive to errors in the determination of the position of the orifice. Assuming a hemispheric model, ERO = 2,r2· Vr/Vo (with Vo= velocity at the orifice) and (Vo/Vr)0.5= (2,/ERO)0.5r. Thus, the slope of the corresponding linear regression allows ERO to be calculated as: ERO = 2,/slope2. This approach was tested in vitro in pulsatile conditions on circular, conical, and slit-like orifices. The calculated ERO was compared with the actual jet cross sectional area derived from the transverse velocity profile at the jet origin. For the purpose of comparison, the "classical" ERO was calculated for all the configurations, angulations, and threshold velocities. The relationship between (Vo/Vr)0.5 was linear (r > 0.98) over a wide range of velocities. The nonhemispheric components were found to modify the constant and not the slope. The mean variation of the calculated ERO was 6.5%. The correlation between the calculated and the actual ERO was very close (>0.97) with slope equal to 0.96. By comparison with the new method, the classical formula gave an underestimation of the ERO that dramatically increased when studying the flow closer to the orifice or in the case of error on the measurement of r. In conclusion, a method using velocity profiles instead of isolated values improves the accuracy of the proximal isovelocity surface area (PISA) method for measuring the ERO. [source] EDUCATIONAL BENEFITS AND MILITARY SERVICE: AN ANALYSIS OF ENLISTMENT, REENLISTMENT, AND VETERANS' BENEFIT USAGE 1991,2005,ECONOMIC INQUIRY, Issue 4 2010CURTIS J. SIMON Montgomery GI Bill (MGIB) educational benefits are a prime recruiting tool in today's all-volunteer military. This paper studies the effects of changes in education benefits using data of the period 1990,2005. Higher benefits lead to higher separation due to both pure incentive effects and by attracting more college-oriented youth into military service. We deal with potential selection issues by distinguishing between anticipated and unanticipated benefit changes. Higher education benefits are associated with higher separation from the Army and Air Force, but not the other services. A $10,000 increase in MGIB benefits is estimated to increase usage by about 5 percentage points, but the duration of usage is estimated to be insensitive to benefit levels. (JEL H52, I21, J24) [source] Reagentless Glucose Biosensor Based on the Direct Electrochemistry of Glucose Oxidase on Carbon Nanotube-Modified ElectrodesELECTROANALYSIS, Issue 11 2006Xiliang Luo Abstract The direct electrochemistry of glucose oxidase (GOD) was revealed at a carbon nanotube (CNT)-modified glassy carbon electrode, where the enzyme was immobilized with a chitosan film containing gold nanoparticles. The immobilized GOD displays a pair of redox peaks in pH,7.4 phosphate buffer solutions (PBS) with the formal potential of about ,455,mV (vs. Ag/AgCl) and shows a surface-controlled electrode process. Bioactivity remains good, along with effective catalysis of the reduction of oxygen. In the presence of dissolved oxygen, the reduction peak current decreased gradually with the addition of glucose, which could be used for reagentless detection of glucose with a linear range from 0.04 to 1.0,mM. The proposed glucose biosensor exhibited high sensitivity, good stability and reproducibility, and was also insensitive to common interferences such as ascorbic and uric acid. The excellent performance of the reagentless biosensor is attributed to the effective enhancement of electron transfer between enzyme and electrode surface by CNTs, and the biocompatible environment that the chitosan film containing gold nanoparticles provides for immobilized GOD. [source] Othello and the Geography of PersuasionENGLISH LITERARY RENAISSANCE, Issue 1 2010Catherine Nicholson Othello is a revealing commentary on the unstable geographic underpinnings of early modern English theories of persuasion, which vacillate between affirming the authority of the commonplace and recognizing the allure of the novel and the strange. Thomas Rymer attacks the play as a tissue of improbabilities: Rymer's rigidly Aristotelian critique has been dismissed as a willfully insensitive and racist misreading, but his insistence on conflating credibility with racial identity coincides with Othello's own representation of its hero as doubly far-fetched. Othello's strangeness is both the key to his eloquence and the root of his vulnerability to Iago's skillful deployment of insider knowledge and plausible fictions. The play's racial dynamics thus play out rhetorically: Brabantio's locally-specific likelihoods may yield to Othello's exotic figures of speech, but Iago's commonplaces triumph in the end. This contest between plausibility and extravagance doesn't merely echo the play's geographic plotting, it points to the inextricability of early modern ideas about eloquence and about place. (C.N.) [source] Effect of Cu stress on the invertase activity and root growth in two populations of Rumex dentatus L. with different Cu toleranceENVIRONMENTAL TOXICOLOGY, Issue 4 2008Yu Huang Abstract There has been no study on key enzymes in sucrose cleavage in metallophyte plants so far, which may be crucial for the plants' root growth and heavy metal tolerance maintenance. Acid invertases are rate-limiting enzymes in sucrose metabolism. Here, we tested the hypothesis that the roots of copper-tolerant plants should manifest a higher activity of acid invertases than nontolerant plants both for supporting growth and for their maintaining tolerance under Cu stress. Two populations of Rumex dentatus L., one from an ancient waste heap at a Cu mine (Cu-tolerant population), and the other from a noncontaminated site (Cu nontolerant population), were used in the experiments. The seedlings of Rumex dentatus L. were exposed to 0, 10, and 40 ,M CuCl2 for 14 days. Cu exposure had a stronger inhibition on root growth and thus resulted in a lower root/shoot ratio in the plants of nontolerant population compared with the Cu-tolerant population. Cu exposure showed a stronger inhibition of acid invertase activity of Cu nontolerant plants than Cu tolerant plants, whereas neutral/alkaline invertase was insensitive to Cu. A positive correlation between the activity of acid invertases and the root growth and root/shoot ratio was observed. The results suggested that the higher activities in acid invertases of Cu-tolerant population might at least partly associate with the plants' Cu tolerance, and their higher activities in acid invertases in turn played an role in maintenance of the Cu tolerance by supplying carbon and energy for tolerance mechanisms. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Effects of insecticide exposure on feeding inhibition in mayflies and oligochaetesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Alexa C. Alexander Abstract The present study examined the effects of pulse exposures of the insecticide imidacloprid on the mayfly, Epeorus longimanus Eaton (Family Heptageniidae), and on an aquatic oligochaete, Lumbriculus variegatus Müller (Family Lumbriculidae). Pulse exposures of imidacloprid are particularly relevant for examination, because this insecticide is relatively soluble (510 mg/L) and is most likely to be at effect concentrations during runoff events. Experiments examined the recovery of organisms after a 24-h pulse exposure to imidacloprid over an environmentally realistic range of concentrations (0, 0.1, 0.5, 1, 5, and 10 ,g/L). Effects on feeding were measured by quantifying the algal biomass consumed by mayflies or foodstuffs egested by oligochaetes. Imidacloprid was highly toxic, with low 24-h median lethal concentrations (LC50s) in early mayfly instars (24-h LC50, 2.1 ± 0.8 ,g/L) and larger, later mayfly instars (24-h LC50, 2.1 ± 0.5 ,g/L; 96-h LC50, 0.65 ± 0.15 ,g/L). Short (24-h) pulses of imidacloprid in excess of 1 ,g/L caused feeding inhibition, whereas recovery (4 d) varied, depending on the number of days after contaminant exposure. In contrast to mayflies, oligochaetes were relatively insensitive to imidacloprid during the short (24-h) pulse; however, immobility of oligochaetes was observed during a 4-d, continuous-exposure experiment, with 96-h median effective concentrations of 6.2 ± 1.4 ,g/L. Overall, imidacloprid reduced the survivorship, feeding, and egestion of mayflies and oligochaetes at concentrations greater than 0.5 but less than 10 ,g/L. Inhibited feeding and egestion indicate physiological and behavioral responses to this insecticide. [source] Risk assessment of Magnacide® H herbicide at Río Colorado irrigation channels (Argentina). tier 3: Studies on native speciesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2007Andrés Venturino Abstract We evaluated the potential environmental risk of the herbicide Magnacide® (Baker Petrolite, TX, USA) using native species from Argentina, representing the ecosystem at the Irrigation Corporation (CORFO) channels at the Colorado River mouth, Buenos Aires, Argentina. Six species including fish, toads, snails, crustaceans, and insects were selected to perform studies on acute toxicity and repeated exposure effects. Magnacide H susceptibility ranking was Bufo arenarum (lethal concentration 50 [LC50] = 0.023 mg/L), Onchorhynchus mykiss (LC50 = 0.038 mg/L), Heleobia parchappii (LC50 = 0.21 mg/L), Hyalella curvispina (LC50 = 0.24 mg/L), Simulium spp. (LC50 = 0.60 mg/L), and Chironomus spp. (LC50 = 2.83 mg/L). The risk limit of 10th percentile (0.013 mg/L) determined by probit analysis on sensitivity distribution was similar to the one calculated from literature data. Risk assessment based on field application data suggested lethal exposures for more than 70 to 90% of the species up to 20 km downstream from the application point. Repeated exposures to Magnacide H of amphibian larvae at the lowest-observed-effect concentration caused some effects during the first exposure, but without cumulative effects. Amphipods were insensitive to repeated exposures, showing no cumulative effects. Whether short-term exposures may result in long-term sublethal effects on the organism's life history was not addressed by these laboratory tests. In conclusion, tier 3 studies indicate that Magnacide H application schedule is extremely toxic for most native species at CORFO,Río Colorado channels, representing a high potential risk in the environment. The real environmental impact must be addressed by field studies at tier 4 giving more information on population effects and communities. [source] MR imaging of the brain in patients with hepatic form of Wilson's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2003D. Kozi The aim of this study was to detect the sites and frequency of possible lesions by brain magnetic resonance imaging (MRI; 1,5T) in a group of 16 neurologically asymptomatic patients with hepatic form of Wilson's disease (WD; seven untreated and nine under treatment). Abnormal MR findings of the brain were found in 75% of patients. Lesions in brain parenchyma were detected in all untreated, drug-naive patients and in 44% of treated patients. Abnormal signal in globus pallidus, putamen, and caudate nucleus was revealed in 86, 71 and 71% of treated and in 33, 33 and 22% of untreated patients, respectively. In five of eight patients with putaminal pathology (62.5%) and in four of seven patients with caudate nuclei involvement (57%), only proton density 2-weighted sequence (PDW) exhibited sensitivity for lesion detection, with both T1W and long echo T2W sequences being insensitive. This superiority of PDW sequence was even more pronounced in the group of untreated patients in whom 80% of putaminal pathology was visible exclusively on this sequence. The lower frequency of lesions in the group of treated in comparison with untreated patients indicated that they might be reversible in the course of chronic chelating therapy. [source] Early processing in the human lateral occipital complex is highly responsive to illusory contours but not to salient regionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2009Marina Shpaner Abstract Human electrophysiological studies support a model whereby sensitivity to so-called illusory contour stimuli is first seen within the lateral occipital complex. A challenge to this model posits that the lateral occipital complex is a general site for crude region-based segmentation, based on findings of equivalent hemodynamic activations in the lateral occipital complex to illusory contour and so-called salient region stimuli, a stimulus class that lacks the classic bounding contours of illusory contours. Using high-density electrical mapping of visual evoked potentials, we show that early lateral occipital cortex activity is substantially stronger to illusory contour than to salient region stimuli, whereas later lateral occipital complex activity is stronger to salient region than to illusory contour stimuli. Our results suggest that equivalent hemodynamic activity to illusory contour and salient region stimuli probably reflects temporally integrated responses, a result of the poor temporal resolution of hemodynamic imaging. The temporal precision of visual evoked potentials is critical for establishing viable models of completion processes and visual scene analysis. We propose that crude spatial segmentation analyses, which are insensitive to illusory contours, occur first within dorsal visual regions, not the lateral occipital complex, and that initial illusory contour sensitivity is a function of the lateral occipital complex. [source] Metabotropic glutamate receptor 1 activity generates persistent, N -methyl- d -aspartate receptor-dependent depression of hippocampal pyramidal cell excitabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2009J. P. Clement Abstract Metabotropic glutamate receptors (mGluRs) are involved in many forms of neuronal plasticity. In the hippocampus, they have well-defined roles in long-lasting forms of both synaptic and intrinsic plasticity. Here, we describe a novel form of long-lasting intrinsic plasticity that we call (S)-3,5-dihydroxyphenylglycine (DHPG)-mediated long-term depression of excitability (DHPG-LDE), and which is generated following transient pharmacological activation of group I mGluRs. In extracellular recordings from hippocampal slices, DHPG-LDE was expressed as a long-lasting depression of antidromic compound action potentials (cAPs) in CA1 or CA3 cells following a 4-min exposure to the group I mGluR agonist (S)-DHPG. A similar phenomenon was also seen for orthodromic fibre volleys evoked in CA3 axons. In single-cell recordings from CA1 pyramids, DHPG-LDE was manifest as persistent failures in antidromic action potential generation. DHPG-LDE was blocked by (S)-(+)- a -amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), an antagonist of mGluR1, but not 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 inhibitor. Although insensitive to antagonists of ,-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate/kainate and ,-aminobutyric acidA receptors, DHPG-LDE was blocked by antagonists of N -methyl- d -aspartate (NMDA) receptors. Similarly, in single-cell recordings, DHPG-mediated antidromic spike failures were eliminated by NMDA receptor antagonism. Long after (S)-DHPG washout, DHPG-LDE was reversed by mGluR1 antagonism. A 4-min application of (S)-DHPG also produced an NMDA receptor-dependent persistent depolarization of CA1 pyramidal cells. This depolarization was not solely responsible for DHPG-LDE, because a similar level of depolarization elicited by raising extracellular K+ increased the amplitude of the cAP. DHPG-LDE did not involve HCN channels or protein synthesis, but was eliminated by blockers of protein kinase C or tyrosine phosphatases. [source] Proteolytic cleavage of the voltage-gated Ca2+ channel ,2, subunit: structural and functional featuresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Arturo Andrade Abstract By mediating depolarization-induced Ca2+ influx, high-voltage-activated Ca2+ channels control a variety of cellular events. These heteromultimeric proteins are composed of an ion-conducting (,1) and three auxiliary (,2,, , and ,) subunits. The ,2, subunit enhances the trafficking of the channel complex to the cell surface and increases channel open probability. To exert these effects, ,2, must undergo important post-translational modifications, including a proteolytic cleavage that separates the extracellular ,2 from its transmembrane , domain. After this proteolysis both domains remain linked by disulfide bonds. In spite of its central role in determining the final conformation of the fully mature ,2,, almost nothing is known about the physiological implications of this structural modification. In the current report, by using site-directed mutagenesis, the proteolytic site of ,2, was mapped to amino acid residues Arg-941 and Val-946. Substitution of these residues renders the protein insensitive to proteolytic cleavage as evidenced by the lack of molecular weight shift upon treatment with a disulfide-reducing agent. Interestingly, these mutations significantly decreased whole-cell patch-clamp currents without affecting the voltage dependence or kinetics of the channels, suggesting a reduction in the number of channels targeted to the plasma membrane. [source] Regulated expression of HCN channels and cAMP levels shape the properties of the h current in developing rat hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Rainer Surges Abstract The hyperpolarization-activated current (Ih) contributes to intrinsic properties and network responses of neurons. Its biophysical properties depend on the expression profiles of the underlying hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and the presence of cyclic AMP (cAMP) that potently and differentially modulates Ih conducted by HCN1, HCN2 and/or HCN4. Here, we studied the properties of Ih in hippocampal CA1 pyramidal cells, the developmental evolution of the HCN-subunit isoforms that contribute to this current, and their interplay with age-dependent free cAMP concentrations, using electrophysiological, molecular and biochemical methods. Ih amplitude increased progressively during the first four postnatal weeks, consistent with the observed overall increased expression of HCN channels. Activation kinetics of the current accelerated during this period, consonant with the quantitative reduction of mRNA and protein expression of the slow-kinetics HCN4 isoform and increased levels of HCN1. The sensitivity of Ih to cAMP, and the contribution of the slow component to the overall Ih, decreased with age. These are likely a result of the developmentally regulated transition of the complement of HCN channel isoforms from cAMP sensitive to relatively cAMP insensitive. Thus, although hippocampal cAMP concentrations increased over twofold during the developmental period studied, the coordinated changes in expression of three HCN channel isoforms resulted in reduced effects of this signalling molecule on neuronal h currents. [source] Respiratory responses evoked by blockades of ionotropic glutamate receptors within the Bötzinger complex and the pre-Bötzinger complex of the rabbitEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Donatella Mutolo Abstract The respiratory role of excitatory amino acid (EAA) receptors within the Bötzinger complex (BötC) and the pre-Bötzinger complex (pre-BötC) was investigated in ,-chloralose,urethane anaesthetized, vagotomized, paralysed and artificially ventilated rabbits by using bilateral microinjections (30,50 nL) of EAA receptor antagonists. Blockade of both N -methyl- d -aspartic acid (NMDA) and non-NMDA receptors by 50 mm kynurenic acid (KYN) within the BötC induced a pattern of breathing characterized by low-amplitude, high-frequency irregular oscillations superimposed on tonic phrenic activity and successively the disappearance of respiratory rhythmicity in the presence of intense tonic inspiratory discharges (tonic apnea). KYN microinjections into the pre-BötC caused similar respiratory responses that, however, never led to tonic apnea. Blockade of NMDA receptors by D(,)-2-amino-5-phosphonopentanoic acid (D-AP5; 1, 10 and 20 mm) within the BötC induced increases in respiratory frequency and decreases in peak phrenic amplitude; the highest concentrations caused tonic apnea insensitive to chemical stimuli. Blockade of non-NMDA receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1, 10 and 20 mm) within the BötC produced only less pronounced increases in respiratory frequency. Responses to D-AP5 in the pre-BötC were similar, although less pronounced than those elicited in the BötC and never characterized by tonic apnea. In the same region, CNQX provoked increases in respiratory frequency similar to those elicited in the BötC, associated with slight reductions in peak phrenic activity. The results show that EAA receptors within the investigated medullary subregions mediate a potent control on both the intensity and frequency of inspiratory activity, with a major role played by NMDA receptors. [source] Fractalkine reduces N -methyl- d -aspartate-induced calcium flux and apoptosis in human neurons through extracellular signal-regulated kinase activationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Kumaran Deiva Abstract Our purpose was to investigate in human neurons the neuroprotective pathways induced by Fractalkine (FKN) against glutamate receptor-induced excitotoxicity. CX3CR1 and FKN are expressed constitutively in the tested human embryonic primary neurons and SK-N-SH, a human neuroblastoma cell line. Microfluorometry assay demonstrated that CX3CR1 was functional in 44% of primary neurons and in 70% of SK-N-SH. Fractalkine induced ERK1/2 phosphorylation within 1 min and Akt phosphorylation after 10 min, and both phosphorylation decreased after 20 min. No p38 and SAPK/JNK activation was observed after FKN treatment. Application of FKN triggered a 53% reduction of the NMDA-induced neuronal calcium influx, which was insensitive to pertussis toxin and LY294002 an inhibitor of Akt pathway, but abolished by PD98059, an ERK1/2 pathway inhibitor. Moreover, FKN significantly reduced neuronal NMDA-induced apoptosis, which was pertussis toxin insensitive and abolished in presence of PD98059 and LY294002. In conclusion, FKN protected human neurons from NMDA-mediated excitotoxicity in at least two ways with different kinetics: (i) an early ERK1/2 activation which reduced NMDA-mediated calcium flux; and (ii), a late Akt activation associated with the previously induced ERK1/2 activation. [source] Bidirectional modulation of visual plasticity by cholinergic receptor subtypes in the frog optic tectumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2003Chuan-Jiang Yu Abstract Cholinergic input to the optic tectum is necessary for visual map maintenance. To understand why, we examined the effects of activation of the different cholinergic receptor subtypes in tectal brain slices and determined whether the retinotectal map was affected by manipulations of their activity in vivo. Both ,-bungarotoxin sensitive and insensitive nicotinic receptor agonists increased spontaneous postsynaptic currents (sPSCs) in a subpopulation of patch-clamped tectal cells; application of subtype selective receptor antagonists reduced nicotine-induced increases in sPSCs. Activation of ,-bungarotoxin insensitive nicotinic receptors also induced substantial inward current in some cells. Muscarinic receptor mediated outward current responses were blocked by the M2-like muscarinic receptor antagonists himbacine or AF-DX 384 and mimicked by application of the M2-like agonist oxotremorine. A less frequently observed muscarinic response involving a change in sPSC frequency appeared to be mediated by M1-like muscarinic receptors. In separate experiments, pharmacological manipulation of cholinergic receptor subtype activation led to changes in the activity-dependent visual map created in the tectum by retinal ganglion cell terminals. Chronic exposure of the tectum to either ,-bungarotoxin insensitive, ,-bungarotoxin sensitive or M1-like receptor antagonists resulted in map disruption. However, treatment with the M2-like receptor antagonist, AF-DX 384, compressed the map. We conclude that nicotinic or M1-like muscarinic receptors control input to tectal cells while ,-bungarotoxin insensitive nicotinic receptors and M2-like muscarinic receptors change tectal cell responses to that input. Blockade of the different cholinergic receptor subtypes can have opposing effects on map topography that are consistent with expected effects on tectal cell activity levels. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||