Synthesis and alkyne-coupling chemistry of cyclomanganated 1- and 3-acetylindoles, 3-formylindole and analogues

The syntheses are reported of new cyclomanganated indole derivatives (1-acetyl-κO-indolyl-κC2)dicarbonylbis(trimethylphosphite)manganese (2), (1-methyl-3-acetyl-κO-indolyl-κC2)tetracarbonylmanganese (4), (3-formyl-κO-indolyl-κC2)tetracarbonylmanganese (5a) and (1-methyl-3-formyl-κO-indolyl-κC2)tetracarbonylmanganese (5b). The unusually complicated crystal structure of 5b has been determined, the first for a cyclomanganated aryl aldehyde. The preparations of a mitomycin-related pyrrolo-indole and related products by thermally promoted and oxidatively (Me3NO) initiated alkyne-coupling reactions of the previously known complex (1-acetyl-κO-indolyl-κC2)tetracarbonylmanganese (1) are reported for different alkynes and solvents. X-ray crystal structures are reported for the dimethyl acetylenedicarboxylate coupling product of 1 (dimethyl 1-methyl-l-hydroxypyrrolo[1,2a]-indole-2,3-dicarboxylate; 6a), and an unusually-cyclised triple insertion product 8 from the coupling of acetylene with 4, in which a cyclopentadiene moiety is η3-allyl-coordinated to Mn through only one double bond and an exocyclic carbon, but which rearranges on heating to an η5-cyclopentadienyl complex

Characterisation of the heterotrimeric presynaptic phospholipase A<inf>2</inf> neurotoxin complex from the venom of the common death adder (Acanthophis antarcticus)

While Australo-Papuan death adder neurotoxicity is generally considered to be due to the actions of reversible competitive postsynaptic α-neurotoxins, the neurotoxic effects are often poorly reversed by antivenom or anticholinesterases. This suggests that the venom may contain a snake presynaptic phospholipase A2 (PLA2) neurotoxin (SPAN) that binds irreversibly to motor nerve terminals to inhibit neurotransmitter release. Using size-exclusion liquid chromatography under non-reducing conditions, we report the isolation and characterisation of a high molecular mass SPAN complex, P-elapitoxin-Aa1a (P-EPTX-Aa1a), from the venom of the common death adder Acanthophis antarcticus. Using the chick biventer-cervicis nerve-muscle preparation, P-EPTX-Aa1a (44,698Da) caused inhibition of nerve-evoked twitch contractions while responses to cholinergic agonists and KCl remained unaffected. P-EPTX-Aa1a also produced significant fade in tetanic contractions and a triphasic timecourse of neuromuscular blockade. These actions are consistent with other SPANs that inhibit acetylcholine release. P-EPTX-Aa1a was found to be a heterotrimeric complex composed of α, β and γ-subunits in a 1:1:1 stoichiometry with each subunit showing significant N-terminal sequence homology to the subunits of taipoxin, a SPAN from Oxyuranus s. scutellatus. Like taipoxin, only the α-chain produced any signs of neurotoxicity or displayed significant PLA2 enzymatic activity. Preincubation with monovalent death adder antivenom or suramin, or inhibition of PLA2 activity by incubation with 4-bromophenacyl bromide, either prevented or significantly delayed the onset of toxicity by P-EPTX-Aa1a. However, antivenom failed to reverse neurotoxicity. Early intervention with antivenom may therefore be important in severe cases of envenomation by A. antarcticus, given the presence of potent irreversible presynaptic neurotoxins. © 2010 Elsevier Inc

Sign problems, noise, and chiral symmetry breaking in a QCD-like theory

The Nambu-Jona-Lasinio model reduced to 2+1 dimensions has two different path integral formulations: at finite chemical potential one formulation has a severe sign problem similar to that found in QCD, while the other does not. At large N, where N is the number of flavors, one can compute the probability distributions of fermion correlators analytically in both formulations. In the former case one finds a broad distribution with small mean; in the latter one finds a heavy tailed positive distribution amenable to the cumulant expansion techniques developed in earlier work. We speculate on the implications of this model for QCD.Comment: 16 pages, 5 figures; Published version with minor changes from the origina

Specific inhibition of GPI-anchored protein function by homing and self-association of specific GPI anchors

The functional specificity conferred by glycophosphatidylinositol (GPI) anchors on certain membrane proteins may arise from their occupancy of specific membrane microdomains. We show that membrane proteins with noninteractive external domains attached to the same carcinoembryonic antigen (CEA) GPI anchor, but not to unrelated neural cell adhesion molecule GPI anchors, colocalize on the cell surface, confirming that the GPI anchor mediates association with specific membrane domains and providing a mechanism for specific signaling. This directed targeting was exploited by coexpressing an external domain-defective protein with a functional protein, both with the CEA GPI anchor. The result was a complete loss of signaling capabilities (through integrin–ECM interaction) and cellular effect (differentiation blockage) of the active protein, which involved an alteration of the size of the microdomains occupied by the active protein. This work clarifies how the GPI anchor can determine protein function, while offering a novel method for its modulation

Titan's atmosphere as observed by Cassini/VIMS solar occultations: CH4_4, CO and evidence for C2_2H6_6 absorption

We present an analysis of the VIMS solar occultations dataset, which allows us to extract vertically resolved information on the characteristics of Titan's atmosphere between 100-700 km with a characteristic vertical resolution of 10 km. After a series of data treatment procedures, 4 occultations out of 10 are retained. This sample covers different seasons and latitudes of Titan. The transmittances show clearly the evolution of the haze and detect the detached layer at 310 km in Sept. 2011 at mid-northern latitudes. Through the inversion of the transmission spectra with a line-by-line radiative transfer code we retrieve the vertical distribution of CH$_4$ and CO mixing ratio. The two methane bands at 1.4 and 1.7 {\mu}m are always in good agreement and yield an average stratospheric abundance of $1.28\pm0.08$%. This is significantly less than the value of 1.48% obtained by the GCMS/Huygens instrument. The analysis of the residual spectra after the inversion shows that there are additional absorptions which affect a great part of the VIMS wavelength range. We attribute many of these additional bands to gaseous ethane, whose near-infrared spectrum is not well modeled yet. Ethane contributes significantly to the strong absorption between 3.2-3.5 {\mu}m that was previously attributed only to C-H stretching bands from aerosols. Ethane bands may affect the surface windows too, especially at 2.7 {\mu}m. Other residual bands are generated by stretching modes of C-H, C-C and C-N bonds. In addition to the C-H stretch from aliphatic hydrocarbons at 3.4 {\mu}m, we detect a strong and narrow absorption at 3.28 {\mu}m which we tentatively attribute to the presence of PAHs in the stratosphere. C-C and C-N stretching bands are possibly present between 4.3-4.5 {\mu}m. Finally, we obtain the CO mixing ratio between 70-170 km. The average result of $46\pm16$ ppm is in good agreement with previous studies.Comment: 51 pages, 28 figure

Systematic study of Optical Feshbach Resonances in an ideal gas

Using a narrow intercombination line in alkaline earth atoms to mitigate large inelastic losses, we explore the Optical Feshbach Resonance (OFR) effect in an ultracold gas of bosonic $^{88}$Sr. A systematic measurement of three resonances allows precise determinations of the OFR strength and scaling law, in agreement with coupled-channels theory. Resonant enhancement of the complex scattering length leads to thermalization mediated by elastic and inelastic collisions in an otherwise ideal gas. OFR could be used to control atomic interactions with high spatial and temporal resolution.Comment: Significant changes to text and figure presentation to improve clarity. Extended supplementary material. 4 pages, 4 figures; includes supplementary material 8 pages, 4 figures. Submitted to Physical Review Letter