Carbachol and bradykinin elevate cyclic AMP and rapidly deplete ATP in cultured rat sympathetic neurons

The agonists carbachol (CCh) and bradykinin (BK) and 54 mM KCl (high K+) were among the most potent stimulants of cyclic AMP (cAMP) production in cultured rat sympathetic neurons, measured with the use of a high-fidelity assay developed for small samples. The rise in cAMP evoked by CCh (through muscarinic receptors), BK, and high K+ was inhibited in Ca2(+)-depleted medium (1.3 mM Ca2+ and 2 mM BAPTA or EGTA), which also prevented the sustained rise in [Ca2+]i evoked by each of these stimuli, showing that elevation of cAMP requires extracellular Ca2+ and, possibly, Ca2+ influx. Preliminary results obtained with the novel calmodulin inhibitor CGS 9343B, which blocked the elevation of cAMP, and with the cyclogenase inhibitor indomethacin, which partially blocked the actions of the agonists but not those of high K+, suggest that calmodulin and arachidonate metabolites may be two components of the signaling pathway. In addition to their effects on cAMP metabolism, CCh, muscarine, and BK, but not nicotine, caused a 30-40% decrease in ATP levels. This effect was much greater than that evoked by high K+ and was largely inhibited by CGS 9343B but slightly enhanced in the Ca(+)-depleted medium, showing that agonists are still active in the absence of [Ca2+]o. Thus, agonists that activate phosphoinositide metabolism can also increase cAMP production and substantially deplete cells of ATP. These novel actions may have to be taken into account when the mechanisms by which such agonists regulate cell function are being considered

Ca2+ transients are not required as signals for long-term neurite outgrowth from cultured sympathetic neurons

A method for clamping cytosolic free Ca2+ ([Ca2+]i) in cultures of rat sympathetic neurons at or below resting levels for several days was devised to determine whether Ca2+ signals are required for neurite outgrowth from neurons that depend on Nerve Growth Factor (NGF) for their growth and survival. To control [Ca2+]i, normal Ca2+ influx was eliminated by titration of extracellular Ca2+ with EGTA and reinstated through voltage-sensitive Ca2+ channels. The rate of neurite outgrowth and the number of neurites thus became dependent on the extent of depolarization by KCl, and withdrawal of KCl caused an immediate cessation of growth. Neurite outgrowth was completely blocked by the L type Ca2+ channel antagonists nifedipine, nitrendipine, D600, or diltiazem at sub- or micromolar concentrations. Measurement of [Ca2+]i in cell bodies using the fluorescent Ca2+ indicator fura-2 established that optimal growth, similar to that seen in normal medium, was obtained when [Ca2+]i was clamped at resting levels. These levels of [Ca2+]i were set by serum, which elevated [Ca2+]i by integral of 30 nM, whereas the addition of NGF had no effect on [Ca2+]i. The reduction of [Ca2+]o prevented neurite fasciculation but this had no effect on the rate of neurite elongation or on the number of extending neurites. These results show that neurite outgrowth from NGF-dependent neurons occurs over long periods in the complete absence of Ca2+ signals, suggesting that Ca2+ signals are not necessary for operating the basic machinery of neurite outgrowth

Coexisting Chalcophile and Lithophile Uranium in Qingzhen (EH3) Chondrite

Mineralogical and textural studies of Qingzhen have shown that it is highly unequilibrated and that it contains a population of chondrules and isolated enstatite grains which preserve the record of more oxidizing nebular conditions (Rambaldi et al., 1983, 1984). Even though in the majority of cases these objects have been affected by various degrees of reduction, some still contain silicates with high (up to 10%) FeO contents

State-to-State Differential and Relative Integral Cross Sections for Rotationally Inelastic Scattering of H2O by Hydrogen

State-to-state differential cross sections (DCSs) for rotationally inelastic scattering of H2O by H2 have been measured at 71.2 meV (574 cm-1) and 44.8 meV (361 cm-1) collision energy using crossed molecular beams combined with velocity map imaging. A molecular beam containing variable compositions of the (J = 0, 1, 2) rotational states of hydrogen collides with a molecular beam of argon seeded with water vapor that is cooled by supersonic expansion to its lowest para or ortho rotational levels (JKaKc= 000 and 101, respectively). Angular speed distributions of fully specified rotationally excited final states are obtained using velocity map imaging. Relative integral cross sections are obtained by integrating the DCSs taken with the same experimental conditions. Experimental state-specific DCSs are compared with predictions from fully quantum scattering calculations on the most complete H2O-H2 potential energy surface. Comparison of relative total cross sections and state-specific DCSs show excellent agreement with theory in almost all detailsComment: 46 page

Extended Huckel theory for bandstructure, chemistry, and transport. II. Silicon

In this second paper, we develop transferable semi-empirical parameters for the technologically important material, silicon, using Extended Huckel Theory (EHT) to calculate its electronic structure. The EHT-parameters areoptimized to experimental target values of the band dispersion of bulk-silicon. We obtain a very good quantitative match to the bandstructure characteristics such as bandedges and effective masses, which are competitive with the values obtained within an $sp^3 d^5 s^*$ orthogonal-tight binding model for silicon. The transferability of the parameters is investigated applying them to different physical and chemical environments by calculating the bandstructure of two reconstructed surfaces with different orientations: Si(100) (2x1) and Si(111) (2x1). The reproduced $\pi$- and $\pi^*$-surface bands agree in part quantitatively with DFT-GW calculations and PES/IPES experiments demonstrating their robustness to environmental changes. We further apply the silicon parameters to describe the 1D band dispersion of a unrelaxed rectangular silicon nanowire (SiNW) and demonstrate the EHT-approach of surface passivation using hydrogen. Our EHT-parameters thus provide a quantitative model of bulk-silicon and silicon-based materials such as contacts and surfaces, which are essential ingredients towards a quantitative quantum transport simulation through silicon-based heterostructures.Comment: 9 pages, 9 figure

A tight binding model for water

We demonstrate for the first time a tight binding model for water incorporating polarizable anions. A novel aspect is that we adopt a "ground up" approach in that properties of the monomer and dimer only are fitted. Subsequently we make predictions of the structure and properties of hexamer clusters, ice-XI and liquid water. A particular feature, missing in current tight binding and semiempirical hamiltonians, is that we reproduce the almost two-fold increase in molecular dipole moment as clusters are built up towards the limit of bulk liquid. We concentrate on properties of liquid water which are very well rendered in comparison with experiment and published density functional calculations. Finally we comment on the question of the contrasting densities of water and ice which is central to an understanding of the subtleties of the hydrogen bond

The Ile-84-->Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein.

In plasma the thyroid hormone-binding protein transthyretin (TTR) forms a tight complex with the specific retinol carrier retinol-binding protein (RBP). The Ile-84–>Ser mutation and several other point mutations in TTR are associated with familial amyloidotic polyneuropathy, which is characterized by extracellular depositions of amyloid fibrils mainly consisting of mutated TTRs. The interactions with human RBP of recombinant human normal and Ser-84 TTRs were investigated by monitoring the fluorescence anisotropy of RBP-bound retinol. A nearly negligible affinity of the recombinant Ser-84 TTR for RBP was found. This result indicates the participation of a region on the outer surface of TTR that comprises Ile-84 in the recognition of RBP. In preliminary studies the Ser-84 TTR was the only one among several amyloidogenic variant TTRs to display negligible interaction with RBP. Therefore, in general a substantially altered binding of TTR to RBP is not associated with familial amyloidotic polyneuropathy. Instead, the altered binding of Ser-84 TTR to RBP appears to be responsible for an abnormal plasma transport of RBP. The recombinant normal TTR exhibits binding properties, in its interaction with human RBP, approximately similar to those of TTR purified from human plasma. Two independent and equivalent RBP binding sites on recombinant normal TTR are characterized by a dissociation constant of about 0.4 microM

Electronic structure and the glass transition in pnictide and chalcogenide semiconductor alloys. Part I: The formation of the ppσpp\sigma-network

Semiconductor glasses exhibit many unique optical and electronic anomalies. We have put forth a semi-phenomenological scenario (J. Chem. Phys. 132, 044508 (2010)) in which several of these anomalies arise from deep midgap electronic states residing on high-strain regions intrinsic to the activated transport above the glass transition. Here we demonstrate at the molecular level how this scenario is realized in an important class of semiconductor glasses, namely chalcogen and pnictogen containing alloys. Both the glass itself and the intrinsic electronic midgap states emerge as a result of the formation of a network composed of $\sigma$-bonded atomic $p$-orbitals that are only weakly hybridized. Despite a large number of weak bonds, these $pp\sigma$-networks are stable with respect to competing types of bonding, while exhibiting a high degree of structural degeneracy. The stability is rationalized with the help of a hereby proposed structural model, by which $pp\sigma$-networks are symmetry-broken and distorted versions of a high symmetry structure. The latter structure exhibits exact octahedral coordination and is fully covalently-bonded. The present approach provides a microscopic route to a fully consistent description of the electronic and structural excitations in vitreous semiconductors.Comment: 22 pages, 17 figures, revised version, final version to appear in J. Chem. Phy