73 research outputs found

    Clusters, phason elasticity, and entropic stabilisation: a theory perspective

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    Personal comments are made about the title subjects, including: the relation of Friedel oscillations to Hume-Rothery stabilisation; how calculations may resolve the random-tiling versus ideal pictures of quasicrystals; and the role of entropies apart from tile-configurational.Comment: IOP macros; 8pp, 1 figure. In press, Phil. Mag. A (Proc. Intl. Conf. on Quasicrystals 9, Ames Iowa, May 2005

    SUMOylation of Syntaxin1A regulates presynaptic endocytosis

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    Neurotransmitter release from the presynaptic terminal is under very precise spatial and temporal control. Following neurotransmitter release, synaptic vesicles are recycled by endocytosis and refilled with neurotransmitter. During the exocytosis event leading to release, SNARE proteins provide most of the mechanical force for membrane fusion. Here, we show one of these proteins, Syntaxin1A, is SUMOylated near its C-terminal transmembrane domain in an activity-dependent manner. Preventing SUMOylation of Syntaxin1A reduces its interaction with other SNARE proteins and disrupts the balance of synaptic vesicle endo/exocytosis, resulting in an increase in endocytosis. These results indicate that SUMOylation regulates the emerging role of Syntaxin1A in vesicle endocytosis, which in turn, modulates neurotransmitter release and synaptic function

    Experience-Driven Axon Retraction in the Pharmacologically Inactivated Visual Cortex Does Not Require Synaptic Transmission

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    BACKGROUND: Experience during early postnatal development plays an important role in the refinement of specific neural connections in the brain. In the mammalian visual system, altered visual experiences induce plastic adaptation of visual cortical responses and guide rearrangements of afferent axons from the lateral geniculate nucleus. Previous studies using visual deprivation demonstrated that the afferents serving an open eye significantly retract when cortical neurons are pharmacologically inhibited by applying a gamma-aminobutyric acid type A receptor agonist, muscimol, whereas those serving a deprived eye are rescued from retraction, suggesting that presynaptic activity can lead to the retraction of geniculocortical axons in the absence of postsynaptic activity. Because muscimol application suppresses the spike activity of cortical neurons leaving transmitter release intact at geniculocortical synapses, local synaptic interaction may underlie the retraction of active axons in the inhibited cortex. METHOD AND FINDINGS: New studies reported here determined whether experience-driven axon retraction can occur in the visual cortex inactivated by blocking synaptic inputs. We inactivated the primary visual cortex of kittens by suppressing synaptic transmission with cortical injections of botulinum neurotoxin type E, which cleaves a synaptic protein, SNAP-25, and blocks transmitter release, and examined the geniculocortical axon morphology in the animals with normal vision and those deprived of vision binocularly. We found that afferent axons in the animals with normal vision showed a significant retraction in the inactivated cortex, as similarly observed in the muscimol-treated cortex, whereas the axons in the binocularly deprived animals were preserved. CONCLUSIONS: Therefore, the experience-driven axon retraction in the inactivated cortex can proceed in the absence of synaptic transmission. These results suggest that presynaptic mechanisms play an important role in the experience-driven refinement of geniculocortical axons

    Regulation of STIM1 and SOCE by the Ubiquitin-Proteasome System (UPS)

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    The ubiquitin proteasome system (UPS) mediates the majority of protein degradation in eukaryotic cells. The UPS has recently emerged as a key degradation pathway involved in synapse development and function. In order to better understand the function of the UPS at synapses we utilized a genetic and proteomic approach to isolate and identify novel candidate UPS substrates from biochemically purified synaptic membrane preparations. Using these methods, we have identified Stromal interacting molecule 1 (STIM1). STIM1 is as an endoplasmic reticulum (ER) calcium sensor that has been shown to regulate store-operated Ca2+ entry (SOCE). We have characterized STIM1 in neurons, finding STIM1 is expressed throughout development with stable, high expression in mature neurons. As in non-excitable cells, STIM1 is distributed in a membranous and punctate fashion in hippocampal neurons. In addition, a population of STIM1 was found to exist at synapses. Furthermore, using surface biotinylation and live-cell labeling methods, we detect a subpopulation of STIM1 on the surface of hippocampal neurons. The role of STIM1 as a regulator of SOCE has typically been examined in non-excitable cell types. Therefore, we examined the role of the UPS in STIM1 and SOCE function in HEK293 cells. While we find that STIM1 is ubiquitinated, its stability is not altered by proteasome inhibitors in cells under basal conditions or conditions that activate SOCE. However, we find that surface STIM1 levels and thapsigargin (TG)-induced SOCE are significantly increased in cells treated with proteasome inhibitors. Additionally, we find that the overexpression of POSH (Plenty of SH3ā€²s), an E3 ubiquitin ligase recently shown to be involved in the regulation of Ca2+ homeostasis, leads to decreased STIM1 surface levels. Together, these results provide evidence for previously undescribed roles of the UPS in the regulation of STIM1 and SOCE function

    Synaptic AMPA receptor composition in development, plasticity and disease

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    Transport of Pb and Zn by carboxylate complexes in basinal ore fluids and related petroleum-field brines at 100Ā°C: the influence of pH and oxygen fugacity

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    It is well established through field observations, experiments, and chemical models that oxidation (redox) state and pH exert a strong influence on the speciation of dissolved components and the solubility of minerals in hydrothermal fluids. log [Image: see text] ā€“pH diagrams were used to depict the influence of oxygen fugacity and pH on monocarboxylate- and dicarboxylate-transport of Pb and Zn in low-temperature (100Ā°C) hydrothermal ore fluids that are related to diagenetic processes in deep sedimentary basins, and allow a first-order comparison of Pb and Zn transport among proposed model fluids for Mississippi Valley-type (MVT) and red-bed related base metal (RBRBM) deposits in terms of their approximate pH and [Image: see text] conditions. To construct these diagrams, total Pb and Zn concentrations and Pb and Zn speciation were calculated as a function of log [Image: see text] and pH for a composite ore-brine with concentrations of major elements, total sulfur, and total carbonate that approximate the composition of MVT and RBRBM model ore fluids and modern basinal brines. In addition to acetate and malonate complexation, complexes involving the ligands Cl(-), HS(-), H(2)S, and OH(- )were included in the model of calculated total metal concentration and metal speciation. Also, in the model, Zn and Pb are competing with the common-rock forming metals Ca, Mg, Na, Fe, and Al for the same ligands. Calculated total Pb concentration and calculated total Zn concentration are constrained by galena and sphalerite solubility, respectively. Isopleths, in log [Image: see text] ā€“pH space, of the concentration of Pb and concentration of Zn in carboxylate (acetate + malonate) complexes illustrate that the oxidized model fluids of T. H. Giordano (in Organic Acids in Geological Processes, ed. E. D. Pittman and M. D. Lewan, Springer-Verlag, New York, 1994, pp. 319ā€“354) and G. M. Anderson (Econ. Geol., 1975, 70, 937ā€“942) are capable of transporting sufficient amounts of Pb (up to 10 ppm) and Zn (up to 100 ppm) in the form of carboxylate complexes to form economic deposits of these metals. On the other hand, the reduced ore fluid models of D. A. Sverjensky (Econ. Geol., 1984, 79, 23ā€“37) and T. H. Giordano and H. L. Barnes (Econ. Geol., 1981, 76, 2200ā€“2211) can at best transport amounts of Pb and Zn, as carboxylate complexes, that are many orders of magnitude below the 1 to 10 ppm minimum required to form economic deposits. Lead and zinc speciation (mol% of total Pb or Zn) in the model ore fluid was calculated at specific log [Image: see text] ā€“pH conditions along the 100, 0.01, and 0.001 ppm total Pb and total Zn isopleths. Along the 100 ppm isopleth conditions are oxidized (āˆ‘SO(4 )>> āˆ‘H(2)S) with Pb and Zn predominantly in the form of chloride complexes under acid to mildly alkaline conditions (pH from 3 to approximately 7.5), while hydroxide complexes dominate Pb and Zn speciation under more alkaline conditions. Sulfide complexes are insignificant under these oxidized conditions. For more reduced conditions along the 0.01 and 0.001 ppm isopleths chloride complexes dominate Pb and Zn speciation in the SO(4)(2- )field and near the SO(4)(2-)-reduced sulfur boundary from pH = 4 to approximately 7.5, while hydroxide complexes dominate Pb and Zn speciation under alkaline conditions above pH = 7.5 in the SO(4)(2- )field. In the most reduced fluids (āˆ‘H(2)S >> āˆ‘SO(4)) along the 0.01 and 0.001 isopleths, sulfide complexes account for almost 100% of the Pb and Zn in the model fluid. Acetate (monocarboxylate) complexation is significant only under conditions of chloride and hydroxide complex dominance and its effect is maximized in the pH range 5 to 7, where it complexes 2 to 2.6% of the total Pb and 1 to 1.25% of the total Zn. Malonate (dicarboxylate) complexes are insignificant along all isopleths. The speciation results from this study show that deep formation waters characterized by temperatures near 100Ā°C, high oxidation states and āˆ‘H(2)S < 0.03 mg L(-1 )([Image: see text] < 10(-6)), high chlorinities (~ 100000 mg L(-1)), and high but reasonable concentrations of carboxylate anions can mobilize up to 3% of the total Pb and up to 1.3% of the total Zn as carboxylate complexes. Furthermore, these percentages, under the most favorable conditions, correspond to approximately 1 to 100 ppm of these metals in solution; concentrations that are adequate to form economic deposits of these metals. However, the field evidence suggests that all of these optimum conditions for carboxylate complexation are rarely met at the same time. A comparison of the composite ore fluid compositions from this study and modern brine data shows that the ore brines, corresponding to log [Image: see text] ā€“pH conditions based on the Anderson (1975) and Giordano (1994) model fluids, are similar in many respects to modern, high trace-metal petroleum-field brines. The principal differences between modern high trace-metal brines and the composite ore fluids of Anderson (1975) and Giordano (1994) relate to their carboxylate anion content. The reported concentrations of monocarboxylate anions (āˆ‘monocbx) and dicarboxylate anions (Edicbx) in high trace-metal petroleum-field brines (< 1 to 300 mg L(-1 )and < 1 mg L(-1), respectively) are significantly lower than the concentrations assumed in the modelled brines of this study (āˆ‘monocbx = 7 700 mg L(-1 )and āˆ‘dicbx = 300 mg L(-1)). There are also major differences in the corresponding total chloride to carboxylate ratio (āˆ‘m(Cl)/āˆ‘m(cbx)) and monocarboxylate to dicarboxylate ratio (āˆ‘m(monocbx)/āˆ‘m(dicbx)). Modern high trace-metal brines have much higher āˆ‘m(Cl)/āˆ‘m(cbx )values and, therefore, the contribution of carboxylate complexes to the total Pb and Zn content in these modern brines is likely to be significantly less than the 1 to 3 percent for the composite ore fluids of Anderson (1975) and Giordano (1994). The composite ore-brine based on the Giordano and Barnes (1981) MVT ore fluid is comparable to the high salinity (> 170 000 mg L(-1 )TDS) subset of modern brines characterized by low trace-metal content and high total reduced sulfur (āˆ‘H(2)S). A comparison of the Sverjensky (1984) composite ore-brine with modern petroleum-field brines in terms of āˆ‘H(2)S and Zn content, reveals that this ore fluid corresponds to a "border-type" brine, between modern high trace-metal brines and those with low trace-metal content and high āˆ‘H(2)S. A brine of this type is characterized by values of āˆ‘H(2)S, āˆ‘Zn, and/or āˆ‘Pb within or near the 1 to 10 mg L(-1 )range. Based on brine-composition data from numerous references cited in this paper, border-type brines do exist but are rare. The model results and field evidence presented in this study are consistent with other chemical simulation studies of carboxylate complexation in modern petroleum-field brines. Thus, it appears that carboxylate complexation plays a minor, if not insignificant, role as a transport mechanism for Pb and Zn in high salinity Naā€“Cl and Naā€“Caā€“Cl basinal brines and related ore fluids

    Directed Self-Assembly: Expectations and Achievements

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    Nanotechnology has been a revolutionary thrust in recent years of development of science and technology for its broad appeal for employing a novel idea for relevant technological applications in particular and for mass-scale production and marketing as common man commodity in general. An interesting aspect of this emergent technology is that it involves scientific research community and relevant industries alike. Topā€“down and bottomā€“up approaches are two broad division of production of nanoscale materials in general. However, both the approaches have their own limits as far as large-scale production and cost involved are concerned. Therefore, novel new techniques are desired to be developed to optimize production and cost. Directed self-assembly seems to be a promising technique in this regard; which can work as a bridge between the topā€“down and bottomā€“up approaches. This article reviews how directed self-assembly as a technique has grown up and outlines its future prospects

    Diretrizes para cessaĆ§Ć£o do tabagismo - 2008

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    Synaptic AMPA receptor composition in development, plasticity and disease

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