Exploiting the Catenane Mechanical Bond Effect for Selective Halide Anion Transmembrane Transport

The first examples of [2]catenanes capable of selective anion transport across a lipid bilayer are reported. The neutral halogen bonding (XB) [2]catenanes were prepared via a chloride template-directed strategy in an unprecedented demonstration of using XB⋅⋅⋅anion interactions to direct catenane assembly from all-neutral components. Anion binding experiments in aqueous-organic solvent media revealed strong halide over oxoanion selectivity, and a marked enhancement in the chloride and bromide affinities of the catenanes relative to their constituent macrocycles. The catenanes additionally displayed an anti-Hofmeister binding preference for bromide over the larger iodide anion, illustrating the efficacy of employing sigma-hole interactions in conjunction with the mechanical bond effect to tune receptor selectivity. Transmembrane anion transport studies conducted in POPC LUVs revealed that the catenanes were more effective anion transporters than the constituent macrocycles, with high chloride over hydroxide selectivity, which is critical to potential therapeutic applications of anionophores. Remarkably these outperform existing acyclic halogen bonding anionophores with regards to this selectivity. Record chloride over nitrate anion transport selectivity was also observed. This represents a rare example of the direct translation of intrinsic anion binding affinities to anion transport behaviour, and demonstrates the key role of the catenane mechanical bond effect for enhanced anion transport selectivity.     

Comment on "Free energy simulations of single and double ion occupancy in gramicidin A" [J. Chem. Phys. 126, 105103 (2007)

In a recent article published by Bastug and Kuyucak [J. Chem. Phys.126, 105103 (2007)] investigated the microscopic factors affecting double ion occupancy in the gramicidin channel. The analysis relied largely on the one-dimensional potential of mean force of ions along the axis of the channel (the so-called free energy profile of the ion along the channel axis), as well as on the calculation of the equilibrium association constant of the ions in the channel binding sites. It is the purpose of this communication to clarify this issue.     

Measurement of the binding of cholera toxin to GM1 gangliosides on solid supported lipid bilayer vesicles and inhibition by europium (III) chloride

In this paper the immobilization of small unilamellar DMPC/GM1 lipid vesicles containing a water-soluble bodipy dye is described. The binding of the complete alphabeta toxin expressed by Vibrio cholerae to the attached vesicles was measured using Surface Plasmon Resonance (SPR) and a value of the dissociation constant K d obtained. Further measurements showed that the interaction of both the alphabeta-toxin and the beta-subunit alone resulted in the permeation of the lipid membrane, with release of a fluorophore contained within the vesicle being measured by combined SPR and Surface Plasmon enhanced Fluorescence Spectroscopy (SPFS). The leakage of dye through the membrane, measured by following the change in fluorescence, was fitted to a simple diffusion model. Finally, SPFS measurements of the effect of europium(III) chloride (EuCl 3) showed that cholera toxin binding and subsequent membrane permeation could be blocked by 1 micromol dm (-3) europium chloride. In view of the low oral toxicity of europium chloride, we speculate on the potential pharmaceutical applications of this molecule in the treatment of cholera infection.     

STATUS DIFFERENTIATION AND THE COHESION OF SOCIAL NETWORKS

This article examines the effects of status differentiation on the cohesion of a social structure. Using a formal model, we simulate the fates of a hypothetical cohort of newly hired employees, who are equals in the eyes of their boss and in the nascent stages of sorting into a status hierarchy. We cast these employees in a process in which they exert effort, receive public approval from the boss in exchange, and thus come to fill different places in a status order. We then consider the circumstances under which these workers cohere as a group and when, by contrast, differentiation makes cohesion among them unlikely. Our results show that the extent of the boss's autonomy in relationship to employees accounts for this difference in outcomes. Under an autonomous boss, as differentiation transpires, status-based social forces break the group of workers apart. Conversely, when the boss occupies a compromised position, group-level cohesion coexists with differentiation. Our main contribution is the intuition that the cohesion-related consequences of status differentiation can substantially depend on the tie between contestants and their external audience. We conclude by developing conjectures for empirical research consistent with our main findings.     

Charge transfer enhanced annihilation leading to deterministic single photon emission in rigid perylene end-capped polyphenylenes

Two new peryleneimide end-capped polyphenylenes are shown to be deterministic single photon sources in PMMA films due to efficient annihilation between charge transfer states.     

The CMSSM parameter space at large tanβ

We extend previous combinations of LEP and cosmological relic density constraints on the parameter space of the constrained MSSM, with universal input supersymmetry-breaking parameters, to large tanβ. We take account of the possibility that the lightest Higgs boson might weigh about 115 GeV, but also retain the possibility that it might be heavier. We include the most recent implementation of the b→sγ constraint at large tanβ. We refine previous relic density calculations at large tanβ by combining a careful treatment of the direct-channel Higgs poles in annihilation of pairs of neutralinos χ with a complete treatment of χ– coannihilation, and discuss carefully uncertainties associated with the mass of the b quark. We find that coannihilation and pole annihilations allow the CMSSM to yield an acceptable relic density at large tanβ, but it is consistent with all the constraints only if m_χ>140 (180) GeV for μ>0 (μ<0) for our default choices  GeV, m_t=175 GeV, and A₀=0.     

Targeted data acquisition for improved reproducibility and robustness of proteomic mass spectrometry assays

Quantitative mass spectrometry-based proteomic assays often suffer from a lack of robustness and reproducibility. We here describe a targeted mass spectrometric data acquisition strategy for affinity enriched subproteomes—in our case the kinome—that enables a substantially improved reproducibility of detection, and improved quantification via isobaric tags. Inclusion mass lists containing m/z, charge state, and retention time were created based on a set of 80 shotgun-type experiments performed under identical experimental conditions. For each target protein, peptides were selected according to their frequency of observation and isobaric tag for relative and absolute quantitation (iTRAQ) reporter ion quality. Retention times of selected peptides were aligned using similarity driven pairwise alignment strategy yielding <1 min standard deviation for 4 h gradients. Multiple fragmentation of the same peptides resulted in better statistics and more precise reporter ion based quantification without any loss in coverage. Overall, 24% more target proteins were quantified using the targeted data acquisition approach, and precision of quantification improved by >1.5-fold. We also show that a combination of higher energy collisional dissociation (HCD) with collisional induced dissociation (CID) outperformed pulsed-Q-dissociation (PQD) on the OrbitrapXL. With the CID/ HCD based targeted data acquisition approach 10% more quantifiable target proteins were identified and a 2-fold increase in quantification precision was achieved. We have observed excellent reproducibility between different instruments, underlining the robustness of the approach.     

An electrochemical impedance study of the effect of pathogenic bacterial toxins on tethered bilayer lipid membrane

Pathogenic bacteria secrete various virulence factors that can directly interact with the outer lipid bilayer membrane of eukaryotic cells, inducing cell death by apoptosis or necrosis. Such virulence factors account for much of the toxic action associated with bacterial infection; therefore the detection of such proteins could provide a methodology for sensing/detection of pathogenic bacteria in, for example, food or human tissue. Detection and identification of pathogenic bacteria by conventional methods such as plating and counting in laboratory is expensive and time consuming. With growing concerns over emergence and re-emergence of pathogenic bacteria with high resistant to current antibiotics, there is a potential need for effective detection of pathogenic toxins in-vitro. This paper presents the application of tethered bilayer lipid membrane (TBLM) as a sensing platform for the detection of the clinically relevant pathogenic bacterial, Staphylococcus aureus MSSA 476 and Pseudomonas aeruginosa PAO1 via their secreted virulence factors, using electrochemical impedance spectroscopy (EIS). A non-pathogenic strain of bacteria, E. coli DH5α was used as a control. A clear difference in the impedance of the TBLM for the pathogenic vs. non-pathogenic species was observed.     

Influence of graphene reinforcement in conductive polymer: Synthesis and characterization

Lightweight conductive polymers are considered for lightning strike mitigation in composites by synthesizing intrinsically conductive polymers (ICPs) and by the inclusion of conductive fillers in insulating matrices. Conductive films based on polyaniline (PANI) and graphene have been developed to improve through‐thickness conductivity of polymer composites. The result shows that the conductivity of PANI enhanced by blending polyvinylpyrrolidone (PVP) and PANI in 3:1 ratio. Conductive composite thin films are prepared by dispersing graphene in PANI. The conductivity of composite films was found to increase by 40× at 20 wt% of graphene inclusion compared with PVP and PANI blend. Fourier‐transform‐infrared (FTIR) spectra confirmed in situ polymerization of the polymer blend. The inclusion of graphene also exhibits an increase in Tg by 21°C. Graphene additions also showed an increase in thermal stability by approximately 148°C in the composite films. The mechanical result obtained from DMA shows that inclusion of graphene increases the tensile strength by 48% at 20 wt% of graphene reinforcement. A thin, highly conductive surface that is compatible with a composite resin system can enhance the surface conductivity of composites, improving its lightning strike mitigation capabilities.     

Incorporation of alpha-hemolysin in different tethered bilayer lipid membrane architectures

Tethered bilayer lipid membranes are stable solid supported model membrane systems. They can be used to investigate the incorporation and function of membrane proteins. In order to study ion translocation mediated via incorporated proteins, insulating membranes are necessary. The architecture of the membrane can have an important effect on both the electrical properties of the lipid bilayer as well as on the possibility to functionally host proteins. Alpha-hemolysin pores have been functionally incorporated into a tethered bilayer lipid membrane coupled to a gold electrode. The protein incorporation has been monitored optically and electrically and the influence of the molecular structure of the anchor lipids on the insertion properties has been investigated.