A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

The inclusion of electrostatic and dispersion interactions into potentials of mean torque for solutes dissolved in uniaxial liquid crystal solvents

A potential of mean torque is derived for a solute at infinite dilution in a uniaxial liquid crystal solvent, which contains terms originating from the dispersion interaction, and the electrostatic interaction between quadrupole moments on both molecules. It is shown that the electrostatic term is non-zero only if the solute-solvent vectors are distributed with lower than spherical symmetry. If this distribution has cylindrical symmetry then both the electrostatic and dispersion terms in the potential of mean torque are shown to depend on order parameters for the orientational distribution of the solute-solvent vectors, as well as on the order parameters of the solvent molecules.     

Certification of the sulphur content of three rapeseed reference materials

Summary The sulphur content of three rapeseed reference materials has been certified on the basis of measurements made by inductively coupled plasma-optical emission spectroscopy, isotope-dilution mass spectrometry and ion chromatography. Their suitability for the calibration of x-ray fluorescence spectrometers used for measuring sulphur in rapeseed samples was established.     

Total surface areas of Group IVA organometallic compounds: Predictors of toxicity to algae and bacteria

There is a high correlation between molecular surface area (TSA) of triorganotin and triorganolead compounds and their toxicity towards a bacterium (Escherichia coli) and an alga (Selenastrum capricornutum). Parallel attempts to correlate other Group IVA organometals incorporating silicon or germanium were unsuccessful. It was further demonstrated, however, that a high correlation was obtainable between certain series of compounds with the same organic substituent but different metal centers involving all Group IVA elements. In both instances, the inability to obtain a quantitative structure-activity relationship (QSAR) for all systems studied appears to be a function of the solubility of the compounds. While organotin TSA values have been found to correlate well with their toxicities toward various organisms, this study clearly suggests that this type of QSAR can be readily extended to include other organometal systems, provided that there is no solubility problem and the toxicity is a function of the hydrophobicity of the organometal compounds.     

Synthesis of 1-(3-alkyl-2,3-dideoxy-D-pentofuranosyl)uracils with potential anti-HIV activity.

1-(3-Alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)uracils and 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-threo-pentofuranosyl)uracils have been prepared from (E)-4,5-di-O-acetyl-2,3-dideoxy-aldehydo-D-glycero-pent-2-enose by a Michael addition reaction of the appropriate organocopper reagent followed in subsequent order by glycosidation of the resulting 3-alkyl-4,5-diacetoxypentanal with methanolic hydrogen chloride, protection with p-methoxybenzoyl chloride, and trimethylsilyl triflate catalyzed coupling with 2,4-di-O-(trimethylsilyl)uracil. The nucleosides were deprotected by treatment with 33% methylamine in absolute ethanol and separated by reversed-phase HPLC.     

Spontaneous photorefractive effect in Sr1−x CaxTiO3 (x=0.014)

The temperature dependence of the principal values of the refractive index in Sr_1−x Ca_xTiO₃ (x=0.014) has been measured in the 17–275 K range under various conditions of sample illumination with 1.96 eV photons. The spontaneous photorefractive contribution δn ^ph to the temperature-induced variation of the refractive index of Sr_1−x Ca_xTiO₃, which appears after illumination of the sample in the ferrophase (transition temperature T _c=32 K) and persists in the paraphase under heating up to 150 K, has been separated. The photoinduced polarization has been estimated. Fiz. Tverd. Tela (St. Petersburg) 39, 711–713 (April 1997)     

Photothermal techniques applied to the determination of the water vapor diffusion coefficient and thermal diffusivity of edible films.

Water vapor diffusion coefficient (WVDC) and thermal diffusivity (alpha) were determined in gelatin-starch films through photothermal techniques. The effect of different variables in the elaboration of these films, such as starch and glycerol concentrations and pH, were evaluated through the response surface methodology. The results indicated that an increase in the glycerol concentration and pH favored the WVDC of the films. On the other hand, alpha was influenced principally by the starch content and pH of the film-forming solution. The minimum alpha value was 4.5 x 10(-4) cm2/s, which is compared with alpha values reported for commercial synthetic polymers.     

Ethylene/1‐hexene copolymerization with tetramethyldisiloxane‐bridged bis(indenyl) metallocenes

Ethylene/1‐hexene copolymerizations with disiloxane‐bridged metallocenes, rac‐ and meso‐1,1,3,3‐tetramethyldisiloxanediyl‐bis(1‐indenyl)zirconium dichloride (rac‐ 1 , meso‐ 1 ) activated by modified methylaluminoxane were performed to investigate the influence of conformational dynamics on comonomer selectivity. Although ¹H NOESY (nuclear Overhauser and exchange spectroscopy) analysis indicated that the most stable conformation for the meso isomer in solution was that in which both indenes project over the metal coordination site, this isomer showed higher 1‐hexene selectivity in copolymerization (r_e = 140 ± 30, r_h = 0.024 ± 0.004) than the rac isomer with only one indene over the coordination site (r_e = 240 ± 20, r_h = 0.005 ± 0.001). The meso isomer showed high 1‐hexene selectivity, a high product of reactivity ratios (r_er_h = 3.3 ± 0.5) and produced copolymers that could be separated into fractions with different ethylene content suggesting that the active species exhibited multisite behavior and populated conformations with different comonomer selectivities during the copolymerization. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3323–3331, 2004