890 resultados para Suppression neuronale


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A systematic x-ray and neutron powder diffraction study of the giant tetragonality multiferroic (1-x) BiFeO3-(x) PbTiO3 have revealed that the compositions close to the morphotropic phase boundary present two different structural phase transition scenarios on cooling from the cubic phase: (i) cubic -> tetragonal (T-2) + tetragonal (T-1) -> tetragonal (T-1) and (ii) cubic -> tetragonal (T-2) + tetragonal (T-1) + rhombohedral (R3c) -> tetragonal (T-1) + rhombohedral (R3c). The comparatively larger tetragonality (c/a - 1) of the T-1 phase as compared to the coexisting isostructural T-2 phase is shown to be a result of significantly greater degree of overlap of the Pb/Bi-6s and Ti/Fe-3d with the O-2p orbitals as compared to that in the T-2 phase. The formation/suppression of the minor metastable rhombohedral phase seems to be governed by subtle play of local kinetic factors. In the scenario when the minor rhombohedral (R) phase is formed along with the tetragonal phases it is able to accommodate the large transformation stress in the system due to formation of the tetragonal phases, and prevent the solid from disintegration into powder after sintering. When the metastable rhombohedral phase is not formed, the large transformation strain ruptures the grain boundaries leading to fragmentation of the dense solid to powder. (C) 2013 American Institute of Physics. http://dx.doi.org/10.1063/1.4792215]

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Key points center dot Active calcium signal propagation occurs when an initial calcium trigger elicits calcium release through endoplasmic reticulum (ER) receptors. A high concentration of the calcium trigger in thin-calibre dendrites would suppress release of calcium through hippocampal inositol trisphosphate receptors (InsP3Rs). center dot Could the high-density expression of A-type K+ channels in thin-calibre dendrites be a mechanism for inhibiting this suppression, thereby restoring the utility of the ER as a substrate for active calcium propagation? center dot Quantitative analyses involving experimentally constrained models reveal a bell-shaped dependence of calcium released through InsP3Rs on the A-type K+ channel density, during the propagation of a calcium wave. center dot A-type K+ channels regulated the relative contribution of ER calcium to the induction of synaptic plasticity in the presence of model metabotropic glutamate receptors. center dot These results identify a novel form of interaction between active dendrites and the ER membrane and suggest that A-type K+ channels are ideally placed for inhibiting the suppression of InsP3Rs in thin-calibre dendrites. Abstract The A-type potassium current has been implicated in the regulation of several physiological processes. Here, we explore a role for the A-type potassium current in regulating the release of calcium through inositol trisphosphate receptors (InsP3R) that reside on the endoplasmic reticulum (ER) of hippocampal pyramidal neurons. To do this, we constructed morphologically realistic, conductance-based models equipped with kinetic schemes that govern several calcium signalling modules and pathways, and constrained the distributions and properties of constitutive components by experimental measurements from these neurons. Employing these models, we establish a bell-shaped dependence of calcium release through InsP3Rs on the density ofA-type potassium channels, during the propagation of an intraneuronal calcium wave initiated through established protocols. Exploring the sensitivities of calcium wave initiation and propagation to several underlying parameters, we found that ER calcium release critically depends on dendritic diameter and that wave initiation occurred at branch points as a consequence of a high surface area to volume ratio of oblique dendrites. Furthermore, analogous to the role ofA-type potassium channels in regulating spike latency, we found that an increase in the density ofA-type potassium channels led to increases in the latency and the temporal spread of a propagating calcium wave. Next, we incorporated kinetic models for the metabotropic glutamate receptor (mGluR) signalling components and a calcium-controlled plasticity rule into our model and demonstrate thatthe presence of mGluRs induced a leftward shift in a BienenstockCooperMunro-like synaptic plasticity profile. Finally, we show that the A-type potassium current could regulate the relative contribution of ER calcium to synaptic plasticity induced either through 900 pulses of various stimulus frequencies or through theta burst stimulation. Our results establish a novel form of interaction between active dendrites and the ER membrane, uncovering a powerful mechanism that could regulate biophysical/biochemical signal integration and steer the spatiotemporal spread of signalling microdomains through changes in dendritic excitability.

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Hedgehog (HH) signaling is a significant regulator of cell fate decisions during embryogenesis, development, and perpetuation of various disease conditions. Testing whether pathogen-specific HH signaling promotes unique innate recognition of intracellular bacteria, we demonstrate that among diverse Gram-positive or Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly, sustained tumor necrosis factor alpha (TNF-alpha) secretion by macrophages was essential for robust SHH activation, as TNF-alpha(-/-) macrophages exhibited compromised ability to activate SHH signaling. Neutralization of TNF-alpha or blockade of TNF-alpha receptor signaling significantly reduced the infection-induced SHH signaling activation both in vitro and in vivo. Intriguingly, activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2 (TLR2) signaling events to regulate a battery of genes associated with divergent functions of M1/M2 macrophages. Genome-wide expression profiling as well as conventional gain-of-function or loss-of-function analysis showed that SHH signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH signaling signatures could be detected in vivo in tuberculosis patients and M. bovis BCG-challenged mice. Collectively, these investigations identify SHH signaling to be what we believe is one of the significant regulators of host-pathogen interactions.

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The main theme of this paper is to study the flammability suppression of hydrocarbons by blending with carbon dioxide, and to evaluate these mixtures as possible working fluids in organic Rankine cycle for medium temperature concentrated solar power applications. The analysis takes into account inevitable irreversibilities in the turbine, the pump, and heat exchangers. While the isopentane + CO2 mixture suffers from high irreversibility mainly in the regenerator owing to a large temperature glide, the propane + CO2 mixture performs more or less the same as pure propane albeit with high cycle pressures. In general, large temperature glides at condensing pressures extend the heat recovery into the two-phase dome, which is an advantage. However, at the same time, the shift of the pinch point towards the warm end of the regenerator is found to be a major cause of irreversibility. In fact, as the number of carbon atoms in alkanes decreases, their blend with CO2 moves the pinch point to the colder end of the regenerator. This results in lower entropy generation in the regenerator and improved cycle efficiency of propane + CO2 mixtures. With this mixture, real cycle efficiencies of 15-18% are achievable at a moderate source temperature of 573 K. Applicability for a wide range of source temperatures is found to be an added advantage of this mixture.

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Silicon nanowires were grown on Si substrates by electron beam evaporation (EBE) was demonstrated using Indium as an alternate catalyst to gold. We have studied the effect of substrate (growth) temperature, deposition time on the growth of nanowires. It was observed that a narrow temperature window from 300 degrees C to 400 degrees C for the nanowires growth. At growth temperature >= 400 degrees C suppression of nanowires growth was observed due to evaporation of catalyst particle. It is also observed that higher deposition times also leading to the absence of nanowire growth as well as uncatalyzed deposition on the nanowires side walls due to limited surface diffusion of ad atoms and catalyst evaporation.

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Pathogenic mycobacteria employ several immune evasion strategies such as inhibition of class II transactivator (CIITA) and MHC-II expression, to survive and persist in host macrophages. However, precise roles for specific signaling components executing down-regulation of CIITA/MHC-II have not been adequately addressed. Here, we demonstrate that Mycobacterium bovis bacillus Calmette-Guerin (BCG)-mediated TLR2 signaling-induced iNOS/NO expression is obligatory for the suppression of IFN-gamma-induced CIITA/MHC-II functions. Significantly, NOTCH/PKC/MAPK-triggered signaling cross-talk was found critical for iNOS/NO production. NO responsive recruitment of a bifunctional transcription factor, KLF4, to the promoter of CIITA during M. bovis BCG infection of macrophages was essential to orchestrate the epigenetic modifications mediated by histone methyltransferase EZH2 or miR-150 and thus calibrate CIITA/MHC-II expression. NO-dependent KLF4 regulated the processing and presentation of ovalbumin by infected macrophages to reactive T cells. Altogether, our study delineates a novel role for iNOS/NO/KLF4 in dictating the mycobacterial capacity to inhibit CIITA/MHC-II-mediated antigen presentation by infected macrophages and thereby elude immune surveillance.

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The subiculum, a para-hippocampal structure positioned between the cornu ammonis 1 subfield and the entorhinal cortex, has been implicated in temporal lobe epilepsy in human patients and in animal models of epilepsy. The structure is characterized by the presence of a significant population of burst firing neurons that has been shown previously to lead epileptiform activity locally. Phase transitions in epileptiform activity in neurons following a prolonged challenge with an epileptogenic stimulus has been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of phase transitions in the burst firing neurons of the subiculum in an in vitro rat brain slice model of epileptogenesis. Whole-cell patch-clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable state was followed by a late suppressed state upon continuous perfusion with epileptogenic 4-aminopyridine and magnesium-free medium. The suppressed state was characterized by inhibitory post-synaptic potentials in pyramidal excitatory neurons and bursting activity in local fast-spiking interneurons at a frequency of 0.1-0.8Hz. The inhibitory post-synaptic potentials were mediated by GABA(A) receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These inhibitory post-synaptic potentials ceased following a cut between the cornu ammonis 1 and subiculum. The suppression of epileptiform activity in the subiculum thus represents a homeostatic response towards the induced hyperexcitability. Our results suggest the importance of feedforward inhibition in exerting this homeostatic control.

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We demonstrate observation of Raman signals of different analytes adsorbed on carbonaceous materials, such as, chemically reduced graphene, graphene oxide (GO), multi-walled carbon nanotube (MWCNT), graphite and activated carbon. The analytes selected for the study were Rhodamine 6G (R6G) (in resonant conditions), Rhodamine B (RB), Nile blue (NBA), Crystal Violet (CV) and acetaminophen (paracetamol). All the analytes except paracetamol absorb and fluoresce in the visible region. In this article we provide experimental evidence of the fact that observation of Raman signals of analytes on such carbonaceous materials are more due to resonance effect, suppression of fluorescence and efficient adsorption and that this property in not unique to graphene or nanotubes but prevalent for various type of carbon materials.

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Background: Genetic variants of NOD2 are linked to inflammatory bowel disease (IBD) etiology. Results: DSS model of colitis in wild-type and inducible nitric-oxide synthase (iNOS) null mice revealed that NOD2-iNOS/NO-responsive microRNA-146a targets NUMB gene facilitating Sonic hedgehog (SHH) signaling. Conclusion: miR-146a-mediated NOD2-SHH signaling regulates gut inflammation. Significance: Identification of novel regulators of IBD provides new insights into pathophysiology and development of new therapy concepts. Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disorder of the intestine. The interactions between enteric bacteria and genetic susceptibilities are major contributors of IBD etiology. Although genetic variants with loss or gain of NOD2 functions have been linked to IBD susceptibility, the mechanisms coordinating NOD2 downstream signaling, especially in macrophages, during IBD pathogenesis are not precisely identified. Here, studies utilizing the murine dextran sodium sulfate model of colitis revealed the crucial roles for inducible nitric-oxide synthase (iNOS) in regulating pathophysiology of IBDs. Importantly, stimulation of NOD2 failed to activate Sonic hedgehog (SHH) signaling in iNOS null macrophages, implicating NO mediated cross-talk between NOD2 and SHH signaling. NOD2 signaling up-regulated the expression of a NO-responsive microRNA, miR-146a, that targeted NUMB gene and alleviated the suppression of SHH signaling. In vivo and ex vivo studies confirmed the important roles for miR-146a in amplifying inflammatory responses. Collectively, we have identified new roles for miR-146a that established novel cross-talk between NOD2-SHH signaling during gut inflammation. Potential implications of these observations in therapeutics could increase the possibility of defining and developing better regimes to treat IBD pathophysiology.

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We demonstrate the electrical transport behavior of carbon nanotubes (CNTs) upon exposure to organic analytes (namely ethanol, benzene, acetone and toluene). The resulting nonlinear current-voltage characteristics revealed a power law dependence of the differential conductivity on the applied bias voltage. Moreover, suppression of differential conductivity at zero bias is found to be dependent on different selective analytes. The power law exponent values have been monitored before, during and after exposure to the chemicals, which revealed a reversible change in the number of electron conducting channels. Therefore, the reduction in the number of conductive paths can be attributed to the interaction of the chemical analyte on the CNT surfaces, which causes a decrease in the differential conductivity of the CNT sample. These results demonstrate chemical selectivity of CNTs due to varying electronic interaction with different chemical analytes.

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Prevention or suppression of protein aggregation is of great importance in the context of protein storage, transportation and delivery. Traditionally chaperones or other chemically active agents are used to stop or diffuse native protein aggregation. We have used gold nanoparticles to prevent thermal aggregation of alcohol dehydrogenase (ADH), a protein that maintains the alcohol level in the liver and stomach. A light-scattering assay has been used to investigate the effect of gold nanoparticles on thermal aggregation of ADH and the result of our study has been summarized in Fig. 1. The scattered light intensity from the solution containing ADH decreases when 45 nm gold nanoparticles are added prior to heating (thermal denaturation) the solution, which indicates prevention of aggregation. The aggregation of the protein is suppressed to the extent of 96% with picomolar concentration of 45 nm gold nanoparticles while micromolar amounts of other proteins and biological substances are necessary to achieve the same effect. The extent varies with the size and the concentration of the gold NPs for the same protein concentration.

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We propose to employ bilateral filters to solve the problem of edge detection. The proposed methodology presents an efficient and noise robust method for detecting edges. Classical bilateral filters smooth images without distorting edges. In this paper, we modify the bilateral filter to perform edge detection, which is the opposite of bilateral smoothing. The Gaussian domain kernel of the bilateral filter is replaced with an edge detection mask, and Gaussian range kernel is replaced with an inverted Gaussian kernel. The modified range kernel serves to emphasize dissimilar regions. The resulting approach effectively adapts the detection mask according as the pixel intensity differences. The results of the proposed algorithm are compared with those of standard edge detection masks. Comparisons of the bilateral edge detector with Canny edge detection algorithm, both after non-maximal suppression, are also provided. The results of our technique are observed to be better and noise-robust than those offered by methods employing masks alone, and are also comparable to the results from Canny edge detector, outperforming it in certain cases.

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The mechanical and electrical characteristics of cellular network of the carbon nanotubes (CNT) impregnated with metallic and nonmetallic nanoparticles were examined simultaneously by employing the nanoindentation technique. Experimental results show that the nanoparticle dispersion not only enhances the mechanical strength of the cellular CNT by two orders of magnitude but also imparts variable nonlinear electrical characteristics; the latter depends on the contact resistance between nanoparticles and CNT, which is shown to depend on the applied load while indentation. Impregnation with silver nanoparticles enhances the electrical conductance, the dispersion with copper oxide and zinc oxide nanoparticles reduces the conductance of CNT network. In all cases, a power law behavior with suppression in the differential conductivity at zero bias was noted, indicating electron tunneling through the channels formed at the CNT-nanoparticle interfaces. These results open avenues for designing cellular CNT foams with desired electro-mechanical properties and coupling. (C) 2014 AIP Publishing LLC.

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The addition of 3 wt% Cu to heat-resistant SUS 304H austenitic steel enhances its high temperature mechanical properties. To further improve the properties, particularly the creep resistance and ductility at high temperatures, a post-solutionizing heat-treatment method that involves an intermediated annealing either at 700 or 800 degrees C after solutionizing for durations up to 180 min was employed. The purpose this heat-treatment is to precipitate planar Cr23C6 at the grain boundaries, which results in the boundaries getting serrated. Detailed microstructural analyses of these `grain boundary engineered' alloys was conducted and their mechanical performance, both at room temperature and at 750 degrees C, was evaluated. While the grain size and texture are unaffected due to the high temperature hold, the volume fraction of Sigma 3 twin boundaries was found to increase significantly. While the strength enhancement was only marginal, the ductility was found to increase significantly, especially at high temperature. A marked increase in the creep resistance was also noted, which is attributed to the reduction of the grain boundary sliding by the grain boundary serrations and the suppression of grain boundary cavitation through the optimization of the volume fraction and spacing of the Cr23C6 precipitates. The special heat-treatment performed with holding time of 3 h at 700 degrees C resulted in the optimum combination of strength, ductility and creep resistance at high temperature. (C) 2014 Elsevier B.V. All rights reserved.

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Anthropogenic fires in seasonally dry tropical forests are a regular occurrence during the dry season. Forest managers in India, who presently follow a fire suppression policy in such forests, would benefit from a system of assessing the potential risk to fire on a particular day. We examined the relationship between weather variables (seasonal rainfall, relative humidity, temperature) and days of fire during the dry seasons of 2004-2010, based on MODIS fire incident data in the seasonally dry tropical forests of Mudumalai in the Western Ghats, southern India. Logistic regression analysis showed that high probabilities of a fire day, indicating successful ignition of litter and grass fuel on the forest floor, were associated with low levels of early dry season rainfall, low daily average relative humidity and high daily average temperatures. These weather conditions are representative of low moisture levels of fine fuels, suggesting that the occurrence of fire is moderated by environmental conditions that reduce the flammability of fine fuels in the dry tropics. We propose a quantitative framework for assessing risk of a fire day to assist forest managers in anticipating fire occurrences in this seasonally dry tropical forest, and possibly for those across South Asia.