Interaction between a cationic surfactant-like peptide and lipid vesicles and its relationship to antimicrobial activity

We investigate the properties of an antimicrobial surfactant-like peptide (Ala)6(Arg), A6R, containing a cationic headgroup. The interaction of this peptide with zwitterionic (DPPC) lipid vesicles is investigated using a range of microscopic, X-ray scattering, spectroscopic, and calorimetric methods. The β-sheet structure adopted by A6R is disrupted in the presence of DPPC. A strong effect on the small-angle X-ray scattering profile is observed: the Bragg peaks from the DPPC bilayers in the vesicle walls are eliminated in the presence of A6R and only bilayer form factor peaks are observed. All of these observations point to the interaction of A6R with DPPC bilayers. These studies provide insight into interactions between a model cationic peptide and vesicles, relevant to understanding the action of antimicrobial peptides on lipid membranes. Notably, peptide A6R exhibits antimicrobial activity without membrane lysis.

Syk-dependent phosphorylation of CLEC-2: a novel mechanism of hem-immunoreceptor tyrosine-based activation motif signalling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors.

The formation mechanism of the Bonin high in August

The Bonin high is a subtropical anticyclone that is predominant near Japan in the summer. This anticyclone is associated with an equivalent-barotropic structure, often extending throughout the entire troposphere. Although the equivalent-barotropic structure of the Bonin high has been known for years among synopticians because of its importance to the summer climate in east Asia, there are few dynamical explanations for such a structure. The present paper attempts to provide a formation mechanism for the deep ridge near Japan. We propose a new hypothesis that this equivalent-barotropic ridge near Japan is formed as a result of the propagation of stationary Rossby waves along the Asian jet in the upper troposphere (‘the Silk Road pattern’). First, the monthly mean climatology is examined in order to demonstrate this hypothesis. It is shown that the enhanced Asian jet in August is favourable for the propagation of stationary Rossby waves and that the regions of descent over the eastern Mediterranean Sea and the Aral Sea act as two major wave sources. Second, a primitive-equation model is used to simulate the climatology of August. The model successfully simulates the Bonin high with an equivalent-barotropic structure. The upper-tropospheric ridge is found to be enhanced by a height anomaly of more than 80 m at 200 hPa, when a wave packet arrives. Sensitivity experiments are conducted to show that the removal of the diabatic cooling over the Asian jet suppresses the Silk Road pattern and formation of an equivalent-barotropic ridge near Japan, while the removal of the diabatic heating in the western Pacific does not. Copyright © 2003 Royal Meteorological Society

The propagation mechanism of a vortex on the β plane

The propagation velocity and propagation mechanism for vortices on a β plane are determined for a reduced-gravity model by integrating the momentum equations over the β plane. Isolated vortices, vortices in a background current, and initial vortex propagation from rest are studied. The propagation mechanism for isolated anticyclones as well as cyclones, which has been lacking up to now, is presented. It is shown that, to first order, the vortex moves to generate a Coriolis force on the mass anomaly of the vortex to compensate for the force on the vortex due to the variation of the Coriolis parameter. Only the mass anomaly of the vortex is of importance, because the Coriolis force due to the motion of the bulk of the layer moving with the vortex is almost fully compensated by the Coriolis force on the motion of the exterior flow. Because the mass anomaly of a cyclone is negative the force and acceleration have opposite sign. The role of dipolar structures in steadily moving vortices is discussed, and it is shown that their overall structure is fixed by the steady westward motion of the mass anomaly. Furthermore, it is shown that reduced-gravity vortices are not advected with a background flow. The reason for this behavior is that the background flow changes the ambient vorticity gradient such that the vortex obtains an extra self-propagation term that exactly cancels the advection by the background flow. Last, it is shown that a vortex initially at rest will accelerate equatorward first, after which a westward motion is generated. This result is independent of the sign of the vortex.

The mechanism of bacterial indigo reduction

The reduction of water-insoluble indigo by the recently isolated moderate thermophile, Clostridium isatidis, has been studied with the aim of developing a sustainable technology for industrial indigo reduction. The ability to reduce indigo was not shared with C. aurantibutyricum, C. celatum and C. papyrosolvens, but C. papyrosolvens could reduce indigo carmine (5,5-indigosulfonic acid), a soluble indigo derivative. The supernatant from cultures of C. isatidis, but not from cultures of the other bacteria tested, decreased indigo particle size to one-tenth diameter. Addition of madder powder, anthraquinone-2,6-disulfonic acid, and humic acid all stimulated indigo reduction by C. isatidis. Redox potentials of cultures of C. isatidis were about 100 mV more negative than those of C. aurantibutyricum, C. celatum and C. papyrosolvens, and reached –600 mV versus the SCE in the presence of indigo, but potentials were not consistently affected by the addition of the quinone compounds, which probably act by modifying the surface of the bacteria or indigo particles. It is concluded that C. isatidis can reduce indigo because (1) it produces an extracellular factor that decreases indigo particle size, and (2) it generates a sufficiently reducing potential.

Investigation of the mechanism of agonist and inverse agonist action at D-2 dopamine receptors

This study investigated, for the D-2 dopamine receptor, the relation between the ability of agonists and inverse agonists to stabilise different states of the receptor and their relative efficacies. K-i values for agonists were determined in competition, versus the binding of the antagonist [H-3]spiperone. Competition data were fitted best by a two-binding site model (with the exception of bromocriptine, for which a one-binding site model provided the best fit) and agonist affinities for the higher (K-h) (G protein-coupled) and lower affinity (K-l) (G protein-uncoupled) sites determined. Ki values for agonists were also determined in competition versus the binding of the agonist [H-3]N-propylnorapomorphine (NPA) to provide a second estimate of K-h,. Maximal agonist effects (E-max) and their potencies (EC50) were determined from concentration-response curves for agonist stimulation of guanosine-5'-O-(3-[S-32] thiotriphosphate) ([S-35]GTPgammaS) binding. The ability of agonists to stabilise the G protein-coupled state of the receptor (K-l/K-h, determined from ligand-binding assays) did not correlate with either of two measures of relative efficacy (relative E-max, Kl/EC50) of agonists determined in [S-35]GTPgammaS-binding assays, when the data for all of the compounds tested were analysed For a subset of compounds, however, there was a relation between K-l/K-h and E-max.. Competition-binding data versus [H-3]spiperone and [H-3]NPA for a range of inverse agonists were fitted best by a one-binding site model. K-i values for the inverse agonists tested were slightly lower in competition versus [H-3]NPA compared to [H-3]spiperone. These data do not provide support for the idea that inverse agonists act by binding preferentially to the ground state of the receptor. (C) 2004 Elsevier Inc. All rights reserved.

First crystallographic signature of an acyclic peptide nanorod: molecular mechanism of nanorod formation by a self-assembled tetrapeptide

A terminally protected acyclic tetrapeptide Boc-Aib-Val-Aib-beta-Ala-OMe 1 (Aib: alpha-aminoisobutyric acid, beta-Ala: beta-Alanine) self-assembles into a continuous hydrogen-bonded supramolecular helix with an average diameter of 10Angstrom (1nm) starting from a double bend molecular conformation in crystals and further self-assembly of this supramolecular architecture leads to the formation of polydisperse nanorods of diameters 10-40 nm.

An insight into the mechanism of protein separation by colloidal gas aphrons (CGA) generated from ionic surfactants

Colloidal gas aphrons (CGA), which are surfactant stabilised microbubbles, have been previously applied for the recovery of proteins from model mixtures and a few studies have demonstrated the potential of these dispersions for the selective recovery of proteins from complex mixtures. However there is a lack of understanding of the mechanism of separation and forces governing the selectivity of the separation. In this paper a mechanistic study is carried out to determine the main factors and forces influencing the selectivity of separation of whey proteins with CGA generated from ionic surfactants. Two different separation strategies were followed: (i) separation of lactoferrin and lactoperoxidase by anionic CGA generated from a solution of sodium bis-(2-ethyl hexyl) sulfosuccinate (AOT); (ii) separation of beta-lactoglobulin by cationic CGA generated from a solution of cetyltrimethylammonium bromide (CTAB). Separation results indicate that electrostatic interactions are the main forces determining the selectivity however these could not completely explain the selectivities obtained following both strategies. Protein-surfactant interactions were studied by measuring the zeta potential changes on individual proteins upon addition of surfactant and at varying pH. Interestingly strongest electrostatic interactions were measured at those pH and surfactant to protein mass ratios which were optimum for protein separation. Effect of surfactant on protein conformation was determined by measuring the change in fluorescence intensity upon addition of surfactant at varying pH. Differences in the fluorescence patterns were detected among proteins which were correlated to differences in their conformational features which could in turn explain their different separation behaviour. The effect of conformation on selectivity was further proven by experiments in which conformational changes were induced by pre-treatment of whey (heating) and by storage at 4 degrees C. Overall it can be concluded that separation of proteins by ionic CGA is driven mainly by electrostatic interactions however conformational features will finally determine the selectivity of the separation with competitive adsorption having also an effect. (c) 2006 Elsevier B.V. All rights reserved.

Phase resetting as a mechanism of ERP generation: evidence from the power spectrum

A Neural Mass model is coupled with a novel method to generate realistic Phase reset ERPs. The power spectra of these synthetic ERPs are compared with the spectra of real ERPs and synthetic ERPs generated via the Additive model. Real ERP spectra show similarities with synthetic Phase reset ERPs and synthetic Additive ERPs.

Pseudogene rescue: an adaptive mechanism of codon reassignment

Alterations to the genetic code – codon reassignments – have occurred many times in life’s history, despite the fact that genomes are coadapted to their genetic codes and therefore alterations are likely to be maladaptive. A potential mechanism for adaptive codon reassignment, which could trigger either a temporary period of codon ambiguity or a permanent genetic code change, is the reactivation of a pseudogene by a nonsense suppressor mutant transfer RNA. I examine the population genetics of each stage of this process and find that pseudogene rescue is plausible and also readily explains some features of extant variability in genetic codes.