Functional coupling of the human dopamine D-2 receptor with G alpha(i1), G alpha(i2), G alpha(i3) and G alpha(o) G proteins: evidence for agonist regulation of G protein selectivity

1 The human dopamine D-2long (D-2L) receptor was expressed with four different G proteins in Sf9 cells using the baculovirus expression system. When co-expressed with G(i)/G(o) G proteins (G(i1)alpha, G(i2)alpha, G(i3)alpha, or G(o)alpha, plus Gbeta(1) and Ggamma(2)) the receptor displayed a high-affinity binding site for the agonists (dopamine and NPA), which was sensitive to GTP (100 mum), demonstrating interaction between the receptor and the different G proteins. 2 The receptor to G protein ratio (R: G ratio) was evaluated using [H-3]-spiperone saturation binding (R) and [S-35]-GTPgammaS saturation binding (G). R: G ratios of 1: 12, 1: 3, 1: 14 and 1: 5 were found for G(i1), G(i2), G(i3), and Go preparations, respectively. However, when R:G ratios of 1:2 and 1: 12 were compared for G(i2) and G(o), no difference was found for the stimulation of [S-35]-GTPgammaS binding. 3 Several agonists were tested for their ability to stimulate [S-35]-GTPgammaS binding to membranes co-expressing the receptor and various G proteins. All the compounds tested showed agonist activity in preparations expressing G(i3) and G(o). However, for G(i2) and G(i1) preparations, compounds such as S-(-)-3-PPP and p-tyramine were unable to stimulate [S-35]-GTPyS binding. 4 Most of the compounds showed higher relative efficacies (compared to dopamine) and higher potencies in the preparation expressing G(o). Comparison of the effects of different agonists in the different preparations showed that each agonist differentially activates the four G proteins. 5 We conclude that the degree of selectivity of G protein activation by the D-2L receptor can depend on the conformation of the receptor stabilised by an agonist.

Report of the inaugural meeting of the TFOS i2 = initiating innovation Series:targeting the unmet need for dry eye treatment

On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i2 = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i2 meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i2 meeting.

Production of Gaseous Radiotracers Ch3i and I2 Through Na123i Salt

The objective of the present work was to develop, separately, methodology for production of two gaseous tracers through the sodium iodide NaI marked with 123I. Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. These two forms of the gaseous iodine, the methyl iodide, CH3I, and molecular iodine, I2, are very unstable and volatile in the ambient temperature and presents different problems in clean-up and monitoring systems. The syntheses were processed with sodium iodide (NaI) 1M aqueous solution marked with 123I. The production of gas I2 was realized with in chlorine acid (HCl) and sodium iodate salt (NaIO3) and the CH3I was used, the salt of NaI and the reagent (CH3)2SO4. The production of gases was initially realized through in unit in glass with an inert material and the purpose was to study the kinetic of reaction and to determine the efficiency of production. The two synthesis occurs in the reaction bottle and after of produced, the gas is stored in the collect bottle that contains a starch solution for fixed the I2, and in syntheses of CH3I contains a silver nitrate solution for your fixation. To determine the efficiency of production of gases, analytic tests were realized, where the consumption of iodide ions of the bottle of reaction are measured. The optimization of production of the each gaseous tracer was studied varying parameter as: concentration of iodide, concentration of acid and temperature. After, the syntheses of the radiotracers were realized in the compact unit, having been used as main reagent the salt radiated of sodium iodide, Na123I. The transportation of elementary iodine and methyl iodine was studied by a scintillation detector NaI (2 x 2)” positioned in the reaction bottle.

Production of Gaseous Tracer I2 from the Sodiumiodide Salt

Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. The iodine is very unstable and volatile in the ambient temperature and the I2 is one of the diverse gaseous forms found. In this work was developed methodology for production of gaseous tracer from the sodium iodide (NaI) 0,1 M marked with 123I. The synthesis was processed with in chlorine acid (HCl) 1M and sodium iodate salt (NaIO3). The production of gas I2 initially was carried through in unit of glass with the inert material and the purpose was to study the kinetic of reaction. The synthesis occurs in the reaction bottle and the produced gas is stored in the collect bottle that contains a starch solution (5 g/100 mL water). To determine the efficiency of production of gas I2, analytic tests had been carried through, where the consumption of iodide ions of the bottle of reaction is measured. The optimization of production of the gaseous tracer was studied varying parameters as: concentration of iodide and iodate, concentration of acid and temperature. Then, the synthesis of the radiotracer was realized in the compact unit, being utilized as main reagent the salt radiated of sodium iodide, Na123I. The transportation of elementary iodine was studied by a scintillation detector NaI (2 x 2)” placed in the reaction bottle. To acquire the data, the detector use a set of electronic modules for the acquisition of signals generated.

A comment on "Inherited Trust and Growth"

Algan and Cahuc (2010) argue that “inherited trust” is a key factor in explaining growth rates across countries. They derive a measure of inherited trust by linking respondents’ “home countries: in the United States General Social Survey (1972-2004) and the 2000 wave of the World Values Survey. Algan and Cahuc then estimate trust levels for people born before 1910 (inherited trust in 1935) and afterwards (inherited trust in 2000). They show a strong link between economic growth rates and inherited trust. We do not challenge this result, but we do argue that: (1) The 2000 World Values Survey has many anomalous results; (2) the estimates for inherited trust in 1935 are mostly based upon tiny samples for most ethnic heritage groups in the General Social Survey; and (3) Algan and Cahuc’s findings are based upon two-tailed rather than one-tailed tests. We reestimate their model using the more reliable waves of the World Values Survey and find much weaker relationships between inherited trust in 1935 and trust in the home country. We also suggest caution in the overall measure of inherited trust in 1935.

Testing the effects of the Japanese vehicle emission-control law on the international palladium futures market

This paper tested the effects of the 2005 vehicle emission-control law issued in Japan on the market linkages between the U.S. and Japanese palladium futures markets, To determine these effects, we applied a cointegration test both with and without break points in the time series and found that the market linkages between the two countries changed after the break in October 2005. Our results show that the 2005 long-term regulation of vehicle emissions enacted in Japan influenced the international palladium futures market.

Tests on price linkage between the U.S. and Japanese gold and silver futures markets

We tested the price linkage, the law of one price (LOP) condition, and the causality of the price linkage between the U.S. and Japanese gold and silver futures markets with consideration of structural breaks in the price series. The LOP condition did not hold for both the gold and silver markets when structural breaks were not considered but it sustained in some periods when it was tested for the break periods. We found from the causality test that the price linkage between the U.S. and Japanese gold and silver futures markets were led by the U.S. market.

Diffusion-driven formation of MoS2 nanotube bundles containing MoS2 nanopods

MoS2 nanotube bundles along with embedded nested fullerenes were formed in a gas phase reaction of molybdenum carbonyl and H2S gas with the assistance of I2. The amorphous Mo-S-I intermediates obtained through quenching a modified MOCVD reaction in a large temperature gradient were annealed at elevated temperature in an inert atmosphere. Under the influence of the iodine the amorphous precursor formed a surface film with an enhanced mobility of the molybdenum and sulfur components. Point defects within the MoS2 layers combined with the enhanced surface diffusion lead to a scrolling of the inherently instable MoS2 lamellae.