177,130 research outputs found
Probing membrane permeabilization by the antibiotic lipopeptaibol trichogin GA IV in a tethered bilayer lipid membrane
No full textAbstractThe lipopeptaibol trichogin GA IV (TCG) can be incorporated in the lipid bilayer moiety of a mercury-supported tethered bilayer lipid membrane (tBLM) at a non-physiological transmembrane potential of about −240mV, negative on the trans side of the bilayer. Once incorporated in the tBLM, TCG is stable over the range of physiological transmembrane potentials and permeabilizes the membrane at transmembrane potentials negative of −80÷−90mV. The chronocoulometric behavior is consistent with a kinetics of nucleation and growth of bundles of TCG building blocks with ion-channel properties. The TCG building blocks also permeabilize the lipid bilayer, albeit at more negative transmembrane potentials, and can be tentatively regarded as dimers of aligned TCG helical monomers. The cyclic voltammograms of tBLMs incorporating TCG point to a voltage-gated behavior of the TCG channel, similar to that exhibited by the peptaibol alamethicin
Au25(SCnH2 n+1)18 Clusters in Biomimetic Membranes: Role of Size, Charge, and Transmembrane Potential in Direct Membrane Permeation
No full textGold nanoclusters and nanoparticles are promising materials for applications in nanomedicine, and therefore, understanding their interaction with cell membranes is of particular importance. A series of neutral and anionic Au25(SCnH2n+1)18 monolayer protected clusters (MPCs) (briefly, Cn0 and Cn- clusters), was embedded into two types of biomimetic membranes supported by mercury electrodes. The first was a dioleoylphosphatidylcholine (DOPC) self-assembled monolayer (SAM), whereas the second was a tethered bilayer lipid membrane (tBLM) obtained by first anchoring a thiolipid monolayer to the mercury surface and then self-assembling a DOPC monolayer on top of it. The diameter of these clusters, from 1.7 to 2.7 nm depending on the thiolate ligand, is smaller than the thickness of biomembranes and biomimetic membranes. Both neutral and anionic Au25(SCnH2n+1)18 MPCs can penetrate the lipid bilayer moiety of the tBLM, without disrupting it; in particular, anionic Au25 clusters require positive transmembrane potentials to do so. Neutral Au25 clusters exchange one electron with mercury in a DOPC SAM, where they can come in contact with the mercury surface, whereas they are prevented from doing so at the tBLM because of their inability to cross the hydrophilic chain separating the lipid bilayer moiety from the mercury surface. The potential of these Au25 clusters to penetrate directly the plasma membrane is particularly convenient for targeted drug delivery. They are highly stable, biocompatible, and catalytic, and their uniform size is of importance in nanomedicine. Moreover, they may induce an efficient energy transfer to 3O2, allowing applications in radiotherapy and antimicrobial activity.
Effect of a Strong Interfacial Electric Field on the Orientationof the Dipole Moment of Thiolated Aib-Oligopeptides Tetheredto Mercury on Either the N- or C-Terminus
No full textFour oligopeptides consisting of a sequence of R-aminoisobutyric acid (Aib) residues, thiolated
at either the N- or C-terminus by means of a -(CH2)2-SH anchor, were self-assembled on mercury, which
is a substrate known to impart a high fluidity to self-assembled monolayers (SAMs). The surface dipole
potential of these peptide SAMs was estimated in 0.1 M KCl aqueous solution at a negatively charged
electrode, where the interfacial electric field is directed toward the metal. To the best of our knowledge,
this is the first estimate of the surface dipole potential of peptide SAMs in aqueous solution. The procedure
adopted consisted in measuring the charge involved in the gradual expansion of a peptide-coated mercury
drop and then combining the resulting information with an estimate of the charge density experienced by
diffuse layer ions. The dipole moment of the tethered thiolated peptides was found to be directed toward
the metal, independent of whether they were thiolated at the C- or N-terminus. This result was confirmed
by the effect of these SAMs on the kinetics and thermodynamics of the Eu(III)/Eu(II) redox couple. The
combined outcome of these studies indicates that a strong interfacial electric field orients the dipole moment
of peptide SAMs tethered to mercury, even against their “natural” dipole moment
A procedure for estimating the surface dipole potential of monolayers adsorbed on electrodes
No full textIncorporation of channel-forming peptides in a Hg-supported lipid bilayer
No full textThe channel-forming peptides gramicidin and alamethicin were incorporated in a mercury-supported lipid bilayer composed of a tethered thiolipid monolayer with a self-assembled dioleoylphosphatidylcholine monolayer on top of it. The thiolipid consists of a hexapeptide chain with a high tendency to form a 310-helical structure, which terminates at the N-terminus end with a sulfydryl group for anchoring to the metal while the C-terminus end is covalently linked to the polar head of dimyristolylphosphatidylethanolamine. The hexapeptide moiety has two triethyleneoxy side chains that impart a satisfactory hydrophilicity and are intended to keep the anchored thiolpeptide chains sufficiently apart, so as to accommodate water molecules and inorganic ions and to create a suitable environment for the incorporation of integral proteins. Changes in the conductance of this biomimetic membrane following the incorporation of gramicidin and alamethicin were detected by impedance spectroscopy. The surface dipole potential of the hexapeptide chain and the transmembrane potential of the lipid bilayer were estimated by using a simple electrostatic model of the mercury|solution interphase
Photoinduced electroreduction of chlorophyllide on alkanethiol-coated mercury
No full textMonolayers of n-alkanethiols of chain length from C-12 to C-18 were self-assembled on a hanging mercury drop electrode, and a film of chlorophyllide (Chlide) was adsorbed on top of them. The reduction photocurrents following illumination of the Chlide film were measured over the potential range in which the Chlide is electroinactive in the dark, and their action spectra were determined. Plotting the derivative of the photocurrents with respect to the applied potential against potential yields bell-shaped curves that can be fitted to a Gaussian. The potential of the Gaussian maximum was used to determine the reorganization energy for the Chlide electroreduction process. An increase in the thiol chain length causes A to decrease regularly and the photocurrent to decay exponentially with the monolayer thickness, with a decay constant beta of about 0. 17 Angstrom(-1)
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Pulmonologist-Administered Balanced Propofol Analgosedation during Interventional Procedures: An Italian Real-Life Study on Comfort and Safety
No full textPropofol-based sedation provides faster recovery than midazolam-based regimens with similar safety and comfort during video flexible bronchoscope (VFB) procedures. Pulmonologist-administered propofol "balanced"analgosedation (PAP-BAS) is still debated in Italy. In this real-life study, PAP-BAS safety and comfort during VFB procedures were investigated. We analysed prospectively the subjects undergoing elective VFB procedures in the Pulmonology and RICU of Arezzo Hospital between February and July 2019. PAP-BAS combined low propofol and meperidine doses titrated to achieve an RASS score between 0 and -3. The primary end-point was the complications' rate. Secondary end-points were as follows: the relation between propofol's dose and a subject's comfort assessed with a VAS, recovery time according to a modified Aldrete score ≥9, RASS, and subjects' will of undergoing the procedure again. We collected postprocedure symptoms' intensity too. Our 158 study patients (67 years; SD ± 14; 64% males) incurred in 25% of complication, fully resolved with medical therapy. Neither recourse to ventilator support nor death was reported. Intraprocedural comfort was good (94% of VAS score ≤2). Among postprocedural symptoms, cough was the most frequently reported, in 36% of the cases. Although half of subjects remembered the procedure, 90% of them would have repeated it, if necessary. 85% of them recovered from procedures within 10 minutes. Complications, VAS, and recovery time were not correlated with propofol dose. To our knowledge, this is the first Italian study showing that PAP-BAS to perform a VFB procedure is safe, well tolerated with a quick recovery. Randomised controlled trials are warranted to confirm these preliminary results
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Tehered bilayer lipid micromembranes for single-channel recording: the role of adsorbed and partially fused vesicles
No full textA mercury-supported bilayer lipid micromembrane was prepared by anchoring a thiolipid monolayer to a mercury cap electrodeposited on a platinum microdisc about 20 mu m in diameter; a lipid monolayer was then self-assembled on top of the thiolipid monolayer either by vesicle fusion or by spilling a few drops of a lipid solution in chloroform on the cap and allowing the solvent to evaporate. Single-channel recording following incorporation of the alamethicin channel-forming peptide exhibits quite different features, depending on the procedure followed to form the distal lipid monolayer. The "spilling" procedure, which avoids the formation of adsorbed or partially fused vesicles, yields very sharp single-channel currents lasting only one or two milliseconds. These are ascribed to ionic flux into the hydrophilic spacer moiety of the thiolipid. Conversely, the vesicle-fusion procedure yields much longer single-channel openings analogous to those obtained with conventional bilayer lipid membranes, albeit smaller. This difference in behavior is explained by ascribing the latter single-channel currents to ionic flux into vesicles adsorbed and/or partially fused onto the tethered lipid bilayer, via capacitive coupling
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