Use of A192621 to provide evidence for involvement of endothelin ET(B)-receptors in endothelin-1-mediated cardiomyocyte hypertrophy.

Increased plasma levels of endothelin-1 correlate with the severity of left ventricular hypertrophy in vivo. The aim of the study was to determine the relative contribution of stimulation of endothelin ETA and endothelin ETB receptors, and the associated activation of protein kinase C, to the hypertrophic response initiated by endothelin-1 in adult rat ventricular cardiomyocytes maintained in culture (24 h). Endothelin-1 (10-7 M) increased the total mass of protein and the incorporation of [14C] phenylalanine into protein to 26% and 25% greater (P

Evidence for two endothelin Et(A) receptor subtypes in rabbit arteriolar smooth muscle.

1. Effects of endothelin-1 (Et-1) were studied on membrane currents in choroidal arteriolar smooth muscle by using perforated patch-clamp recordings. 2. Et-1 (10 nM) activated oscillatory Ca(2+)-activated Cl(-)-currents (I(Cl(Ca))) which could not be reversed by washing out. 3. Currents through L-type Ca(2+) channels were resolved in a divalent free medium (I(Ca(L)Na)). Et-1 reduced I(Ca(L)Na) by 75 +/- 7% within 30 s and this effect faded over 5 min, when the depression remained constant. On washing out Et-1, I(Ca(L)Na) almost completely recovered within 10 s. 4. BQ123 (1 microM), a peptide Et(A) receptor blocker, prevented the activation of I(Cl(Ca)), but failed to inhibit I(Cl(Ca)) transients once they had been initiated. In contrast, BQ123 not only prevented but also reversed the inhibition of I(Ca(L)Na) by Et-1. BQ788 (1 microM), an Et(B) receptor antagonist, did not prevent the activation of I(Cl(Ca)) or the inhibition of I(Ca(L)Na) by Et-1. 5. ABT-627 (10 nM), a non-peptide Et(A) receptor antagonist also blocked the activation of I(Cl(Ca)). However, on I(Ca(L)Na), ABT-627 (10 nM) mimicked the action of Et-1 an effect blocked by BQ123 suggesting that ABT-627 acted as an agonist. 6. The data are consistent with choroidal arteriolar smooth muscle cells having two types of Et(A) receptor, one where BQ123 is an antagonist and ABT-627 an agonist, where ligands dissociate freely and this receptor is coupled to inhibition of L-type Ca(2+) channels. In the other, BQ123 and ABT-627 are both antagonists and with Et-1 the receptor converts to a high affinity state producing the classical irreversible activation I(Cl(Ca)).

Asymmetric Total Synthesis of (+)-Inthomycin C Via O-Directed Free Radical Alkyne Hydrostannation with Phb>3b>SnH and Catalytic Etb>3b>B: Reinstatement of the Zeeck-Taylor (3R)-Structure for (+)-Inthomycin C

A new pathway to (+)-inthomycin C is reported that exploits an O-directed free radical hydrostannation reaction on (−)-12 and a Stille cross-coupling as key steps. Significantly, the latter process was effected on 19 where a gauche-pentane repulsive interaction could interfere. Our stereochemical studies on the alkynol (−)-12 and the enyne (+)-7 confirm that Ryu and Hatakeyama’s (3S)-stereochemical revision of (+)-inthomycin C is invalid and that Zeeck and Taylor’s original (3R)-stereostructure for (+)-inthomycin C is correct.<br/>

Synthesis of the C(7)-C(22)-Sector of (+)-Acutiphycin Via O-Directed Double Free Radical Alkyne Hydrostannation with Phb>3b>SnH/Etb>3b>B, Double I-Sn Exchange and Double Stille Coupling

<br/>Abstract Image<br/><br/>Herein a new double O-directed free radical hydrostannation reaction is reported on the structurally complex dialkyldiyne 11. Through our use of a conformation-restraining acetal to help prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two vinylstannanes of 10 were concurrently constructed with high stereocontrol using Ph3SnH/Et3B/O2. Distannane 10 was thereafter elaborated into the bis-vinyl iodide 9 via O-silylation and double I–Sn exchange; double Stille coupling of 9, O-desilylation, and oxidation thereafter furnished 8.<br/>

B-type supergiants in the SMC: Chemical compositions and comparison of static and unified models

High-resolution UCLES/AAT spectra are presented for nine B-type supergiants in the SMC, chosen on the basis that they may show varying amounts of nuclear-synthetically processed material mixed to their surface. These spectra have been analysed using a new grid of approximately 12 000 non-LTE line blanketed tlusty model atmospheres to estimate atmospheric parameters and chemical composition. The abundance estimates for O, Mg and Si are in excellent agreement with those deduced from other studies, whilst the low estimate for C may reflect the use of the C II doublet at 4267 Å. The N estimates are approximately an order of magnitude greater than those found in unevolved B-type stars or H II regions but are consistent with the other estimates in AB-type supergiants. These results have been combined with results from a unified model atmosphere analysis of UVES/VLT spectra of B-type supergiants (Trundle et al. 2004, A&A, 417, 217) to discuss the evolutionary status of these objects. For two stars that are in common with those discussed by Trundle et al., we have undertaken a careful comparison in order to try to understand the relative importance of the different uncertainties present in such analyses, including observational errors and the use of static or unified models. We find that even for these relatively luminous supergiants, tlusty models yield atmospheric parameters and chemical compositions similar to those deduced from the unified code fastwind.

The VLT-FLAMES survey of massive stars: atmospheric parameters and rotational velocity distributions for B-type stars in the Magellanic Clouds

Aims.We aim to provide the atmospheric parameters and rotational velocities for a large sample of O- and early B-type stars, analysed in a homogeneous and consistent manner, for use in constraining theoretical models. Methods: Atmospheric parameters, stellar masses, and rotational velocities have been estimated for approximately 250 early B-type stars in the Large (LMC) and Small (SMC) Magellanic Clouds from high-resolution VLT-FLAMES data using the non-LTE TLUSTY model atmosphere code. This data set has been supplemented with our previous analyses of some 50 O-type stars (Mokiem et al. 2006, 2007) and 100 narrow-lined early B-type stars (Hunter et al. 2006; Trundle et al. 2007) from the same survey, providing a sample of ~400 early-type objects. Results: Comparison of the rotational velocities with evolutionary tracks suggests that the end of core hydrogen burning occurs later than currently predicted and we argue for an extension of the evolutionary tracks. We also show that the large number of the luminous blue supergiants observed in the fields are unlikely to have directly evolved from main-sequence massive O-type stars as neither their low rotational velocities nor their position on the H-R diagram are predicted. We suggest that blue loops or mass-transfer binary systems may populate the blue supergiant regime. By comparing the rotational velocity distributions of the Magellanic Cloud stars to a similar Galactic sample, we find that (at 3s confidence level) massive stars (above 8 M?) in the SMC rotate faster than those in the solar neighbourhood. However there appears to be no significant difference between the rotational velocity distributions in the Galaxy and the LMC. We find that the v sin i distributions in the SMC and LMC can modelled with an intrinsic rotational velocity distribution that is a Gaussian peaking at 175 km s-1 (SMC) and 100 km s-1 (LMC) with a 1/e half width of 150 km s-1. We find that in NGC 346 in the SMC, the 10-25 M? main-sequence stars appear to rotate faster than their higher mass counterparts. It is not expected that O-type stars spin down significantly through angular momentum loss via stellar winds at SMC metallicity, hence this could be a reflection of mass dependent birth spin rates. Recently Yoon et al. (2006) have determined rates of GRBs by modelling rapidly rotating massive star progenitors. Our measured rotational velocity distribution for the 10-25 M? stars is peaked at slightly higher velocities than they assume, supporting the idea that GRBs could come from rapid rotators with initial masses as low as 14 M? at low metallicities.

The VLT-FLAMES survey of massive stars: atmospheric parameters and rotational velocity distributions for B-type stars in the Magellanic Clouds (vol 457, pg 265, 2006)

We correct the estimates of the dispersions in the rotational velocities for early-type stars in our Galaxy (Dufton et al. 2006, A&A, 457, 265) and the Magellanic Clouds (Hunter et al. 2008, A&A, 479, 541). The corrected values are pi(1/4) (i.e. approximately 33%) larger than those published in the original papers.

The empirical metallicity dependence of the mass-loss rate of O- and early B-type stars

We present a comprehensive study of the observational dependence of the mass-loss rate in stationary stellar winds of hot massive stars on the metal content of their atmospheres. The metal content of stars in the Magellanic Clouds is discussed, and a critical assessment is given of state-of-the-art mass-loss determinations of OB stars in these two satellite systems and the Milky-Way. Assuming a power-law dependence of mass loss on metal content,. M. Z(m), and adopting a theoretical relation between the terminal flow velocity and metal content, v(infinity). Z(0.13) (Leitherer et al. 1992, ApJ, 401, 596), we find m = 0.83 +/- 0.16 for non-clumped outflows from an analysis of the wind momentum luminosity relation (WLR) for stars more luminous than 105.2 L circle dot. Within the errors, this result is in agreement with the prediction m = 0.69 +/- 0.10 by Vink et al. (2001, A& A, 369, 574). Absolute empirical values for the mass loss, based on Ha and ultraviolet (UV) wind lines, are found to be a factor of two higher than predictions in this high luminosity regime. If this difference is attributed to inhomogeneities in the wind, and this clumping does not impact the predictions, this would imply that luminous O and early-B stars have clumping factors in their Ha and UV line forming regions of about a factor of four. For lower luminosity stars, the winds are so weak that their strengths can generally no longer be derived from optical spectral lines (essentially Ha) and one must currently rely on the analysis of UV lines. We confirm that in this low-luminosity domain the observed Galactic WLR is found to be much steeper than expected from theory (although the specific sample is rather small), leading to a discrepancy between UV mass-loss rates and the predictions by a factor 100 at luminosities of L similar to 10(4.75) L circle dot, the origin of which is unknown. We emphasize that even if the current mass-loss rates of hot luminous stars would turn out to be overestimated as a result of wind clumping, but the degree of clumping would be rather independent of metallicity, the scalings derived in this study are expected to remain correct.

A metal deficient early B-type star near the edge of the galactic disk

High resolution spectra of an early B-type star associated with the H II region detected by de Geus et al. (1993) are analysed using LTE model atmosphere techniques to derive stellar atmospheric parameters and a chemical composition. A distance to the star of 8.2 kpc is estimated, placing it near the edge of the galactic disk and closer than the kinematic distance of 20 kpc to the H II region, calculated by de Geus et al. A differential line by line abundance analysis with respect to the spectroscopic standard tau Sco indicates a significant metal depletion, with elements down on average by -0.5 dex.

Some further implications of incorporating the warm glow of giving into welfare measures: A comment on the use of donation mechanisms by Champ et al

Champ er al. [J. Environ. Management 33, 151-162 (1997)] claim that they have (a) explored the welfare implication of warm glow for Hicksian measures of value for public goods and (b) established that actual donations place a

Organizational structure and the periphery of the gene regulatory network in B-cell lymphoma

Background: <br/>The physical periphery of a biological cell is mainly described by signaling pathways which are triggered by transmembrane proteins and receptors that are sentinels to control the whole gene regulatory network of a cell. However, our current knowledge about the gene regulatory mechanisms that are governed by extracellular signals is severely limited.Results: The purpose of this paper is three fold. First, we infer a gene regulatory network from a large-scale B-cell lymphoma expression data set using the C3NET algorithm. Second, we provide a functional and structural analysis of the largest connected component of this network, revealing that this network component corresponds to the peripheral region of a cell. Third, we analyze the hierarchical organization of network components of the whole inferred B-cell gene regulatory network by introducing a new approach which exploits the variability within the data as well as the inferential characteristics of C3NET. As a result, we find a functional bisection of the network corresponding to different cellular components.<br/><br/>Conclusions: <br/>Overall, our study allows to highlight the peripheral gene regulatory network of B-cells and shows that it is centered around hub transmembrane proteins located at the physical periphery of the cell. In addition, we identify a variety of novel pathological transmembrane proteins such as ion channel complexes and signaling receptors in B-cell lymphoma. © 2012 Simoes et al.; licensee BioMed Central Ltd.