Lipid bilayer composition influences small multidrug transporters

Background: Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins. Results: Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr. Conclusion: These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer

Apolipoprotein AIV gene variant S347 is associated with increased risk of coronary heart disease and lower plasma apolipoprotein AIV levels

The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective coronary heart disease (CHD) risk was examined in healthy UK men. Of the 2808 men followed over 9 years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [hazard ratio (HR) of 2.07 (95%CI 1.04 to 4.12)], whereas men homozygous for APOC3 1100T were protected [HR 0.28 (95%CI 0.09 to 0.87)]. In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using all nine SNPs, the highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC3 1100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIV levels, the relationship was examined in 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.64±0.59 mg/dL) compared with carriers of the T347 allele (14.90±0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and around APOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV

Minimizing fouling at hydrogenated conical - tip carbon electrodes during Dopamine detection in vivo

In this paper, physically small conical-tip carbon electrodes (∼2−5 μm diameter and ∼4 μm axial length) were hydrogenated to develop a probe capable of withstanding fouling during dopamine detection in vivo. Upon hydrogenation, the resultant hydrophobic sp3 carbon surface deters adsorption of amphiphilic lipids, proteins, and peptides present in extracellular fluid and hence minimizes electrode fouling. These hydrogenated carbon electrodes showed a 35% decrease in sensitivity but little change in the limit of detection for dopamine over a 7-day incubation in a synthetic laboratory solution containing 1.0% (v/v) caproic acid (a lipid), 0.1% (w/v) bovine serum albumin and 0.01% (w/v) cytochrome C (both are proteins), and 0.002% (w/ v) human fibrinopeptide B (a peptide). Subsequently, during dopamine detection in vivo, over 70% of the dopamine oxidation current remained after the first 30 min of a 60-min experiment, and at least 50% remained over the next half-period at the hydrogenated carbon electrodes. On the basis of these results, an initial average electrode surface fouling rate of 1.2% min−1 was estimated, which gradually declined to 0.7% min−1. These results support minimal fouling at hydrogenated carbon electrodes applied to dopamine detection in vivo

Report on the Distribution of Dwarf Birches and Present Pollen Rain, Baffin Island, N.W.T., Canada

A distribution map for the dwarf birches is presented for the region from Frobisher Bay northward to Cumberland Peninsula. These shrubs are restricted to favourable habitats which, at the northern limit of the species (67 deg. 40 sec. N), are found on south-facing slopes above the immediate local cooling influence of the sea. Pollen studies within the zone of scattered dwarf birch indicate that pollen dispersal from these low, prostrate shrubs is minimal. Samples of moss collected beneath the bushes have 5-36% Betula pollen; whereas sites no more than 50 m away from Betula shrubs have percentages of <2%. These data will be useful in considering the Holocene and Pleistocene histories of these Low Arctic shrubs in the Eastern Canadian Arctic

EVAPORATION OF QUARK DROPS DURING THE COSMOLOGICAL Q-H TRANSITION

We have carried out a study of the hydrodynamics of disconnected quark regions during the final stages of the cosmological quark-hadron transition. A set of relativistic Lagrangian equations is presented for following the evaporation of a single quark drop and results from the numerical solution of this are discussed. A self-similar solution is shown to exist and the formation of baryon number density inhomogeneities at the end of the drop contraction is discussed.Comment: 12 pages Phys. Rev. format, uuencoded postscript file including 12 figure

Collineation group as a subgroup of the symmetric group

Let $\Psi$ be the projectivization (i.e., the set of one-dimensional vector subspaces) of a vector space of dimension $\ge 3$ over a field. Let $H$ be a closed (in the pointwise convergence topology) subgroup of the permutation group $\mathfrak{S}_{\Psi}$ of the set $\Psi$. Suppose that $H$ contains the projective group and an arbitrary self-bijection of $\Psi$ transforming a triple of collinear points to a non-collinear triple. It is well-known from \cite{KantorMcDonough} that if $\Psi$ is finite then $H$ contains the alternating subgroup $\mathfrak{A}_{\Psi}$ of $\mathfrak{S}_{\Psi}$. We show in Theorem \ref{density} below that $H=\mathfrak{S}_{\Psi}$, if $\Psi$ is infinite.Comment: 9 page

The 2dF QSO Redshift Survey - XII. The spectroscopic catalogue and luminosity function

We present the final catalogue of the 2dF QSO Redshift Survey (2QZ), based on Anglo-Australian Telescope 2dF spectroscopic observations of 44 576 colour-selected (ubJr) objects with 18.2