Characterization of the interactions of a polycationic, amphiphilic, terminally branched oligopeptide with lipid A and lipopolysaccharide from the deep rough mutant of Salmonella minnesota

The lipid A and lipopolysaccharide (LPS) binding and neutralizing activities of a synthetic, polycationic, amphiphilic peptide were studied. The branched peptide, designed as a functional analog of polymyxin B, has a six residue hydrophobic sequence, bearing at its N-terminus a penultimate lysine residue whose alpha- and epsilon-amino groups are coupled to two terminal lysine residues. In fluorescence spectroscopic studies designed to examine relative affinities of binding to the toxin, neutralization of surface charge and fluidization of the acyl domains, the peptide was active, closely resembling the effects of polymyxin B and its nonapeptide derivative; however, the synthetic peptide does not induce phase transitions in LPS aggregates as do polymyxin B and polymyxin B nonapeptide. The peptide was also comparable with polymyxin B in its ability to inhibit LPS-mediated IL-l and IL-6 release from human peripheral blood mononuclear cells. The synthetic compound is devoid of antibacterial activities and did not induce conductance fluxes in LPS-containing asymmetric planar membranes. These results strengthen the premise that basicity and amphiphilicity are necessary and sufficient physical properties that ascribe endotoxin binding and neutralizing activities, and further suggest that antibacterial/membrane perturbant and LPS neutralizing activities are dissociable, which may be of value in designing LPS-sequestering agents of low toxicity.

Synthesis and exploration of novel curcumin analogues as anti-malarial agents

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of similar to 3.25 mu M (MIC = 13.2 mu M) and IC50 4.21 mu M (MIC = 14.4 mu M), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 mu M and CQ-R P. falcipartan at IC50 of 0.45 mu M, 0.89, 0.75 mu M, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falcipartan inhibitors and promising candidates for the design of novel anti-malarial agents. (C) 2007 Elsevier Ltd. All rights reserved.

Transition metal complexes of 3-aryl-2-substituted 1,2-dihydroquinazolin-4(3H)-one derivatives: New class of analgesic and anti-inflammatory agents

Five-coordinate, neutral transition metal complexes of newly designed pyridine-2-ethyl-(3-carboxyhdeneamino)-3-(2-phenyl)-1,2-dihydroquinazoli n-4(3H)-one (L) were synthesized and characterized The structure of ligand is confirmed by single crystal X-ray diffraction studies The compounds were evaluated for the anti-inflammatory activity by carrageenan-induced rat paw edema model while their analgesic activity was determined by acetic acid-induced writhing test in mice wherein the transition metal complexes were found to be more active than the free ligand (C) 2010 Elsevier Masson SAS All rights reserved.

Diagnosis of dominant forcing factors for large-scale vertical velocities during active and break phases of the monsoon

An attempt to diagnose the dominant forcings which drive the large-scale vertical velocities over the monsoon region has been made by computing the forcings like diabatic heating fields,etc. and the large-scale vertical velocities driven by these forcings for the contrasting periods of active and break monsoon situations; in order to understand the rainfall variability associated with them. Computation of diabatic heating fields show us that among different components of diabatic heating it is the convective heating that dominates at mid-tropospheric levels during an active monsoon period; whereas it is the sensible heating at the surface that is important during a break period. From vertical velocity calculations we infer that the prime differences in the large-scale vertical velocities seen throughout the depth of the atmosphere are due to the differences in the orders of convective heating; the maximum rate of latent heating being more than 10 degrees Kelvin per day during an active monsoon period; whereas during a break monsoon period it is of the order of 2 degrees Kelvin per day at mid-tropospheric levels. At low levels of the atmosphere, computations show that there is large-scale ascent occurring over a large spatial region, driven only by the dynamic forcing associated with vorticity and temperature advection during an active monsoon period. However, during a break monsoon period such large-scale spatial organization in rising motion is not seen. It is speculated that these differences in the low-level large-scale ascent might be causing differences in convective heating because the weaker the low level ascent, the lesser the convective instability which produces deep cumulus clouds and hence lesser the associated latent heat release. The forcings due to other components of diabatic heating, namely, the sensible heating and long wave radiative cooling do not influence the large-scale vertical velocities significantly.

High-Surface Step Density on Dendritic Pd Leads to Exceptional Catalytic Activity for Formic Acid Oxidation

Dendrite Pd with corrugated surfaces, obtained by a novel AC technique, exhibits an exceptionally high catalytic activity for the oxidation of formic acid because of the presence of a high density of surface steps. The formation of twinned dendrites leads to a predominance of exposed 111 facets with a high density of surface steps as evident from high resolution electron microscopy investigations. These surface sites provide active sites for the absorption of the formic acid molecules, thereby enhancing the reaction rate. Control experiments by varying the time of deposition reveal the formation of partially grown dendrites at shorter times indicating that the dendrites were formed by growth rather than particle attachment. Our deposition method opens up interesting possibilities to produce artisotropic nanostructures with corrugated surfaces by exploiting the perturbations involved in the growth process.

Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing cellular uptake and photocytotoxicity in visible light

Cobalt(II) complexes of terpyridine bases Co(L)(2)](ClO4)(2) (1-3), where L is 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''-terpyridine (an-tpy in 2) and 4'-(1-pyrenyl)-2,2':6',2''-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H2O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K-b value of similar to 10(6) M-1. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC50 values of 24.2 and 7.6 mu M, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.

Porous, catalytically active palladium nanostructures by tuning nanoparticle interactions in an organic medium

We present a simple template-free method for the synthesis of interconnected hierarchical porous palladium nanostructures by controlling the aggregation of nanoparticles in organic media. The interaction between the nanoparticles is tuned by varying the dielectric constant of the medium consistent with DLVO calculations. The reaction products range from discrete nanoparticles to compact porous clusters with large specific surface areas. The nanoclusters exhibit hierarchical porosity and are found to exhibit excellent activity towards the reduction of 4-nitrophenol into 4-aminophenol and hydrogen oxidation. The method opens up possibilities for synthesizing porous clusters of other functional inorganics in organic media.

Effect of surface roughness on diffusion-limited charge transfer

A theory is developed for diffusion-limited charge transfer on a non-fractally rough electrode. The perturbation expressions are obtained for concentration, current density and measured diffusion-limited current for arbitrary one- and two-dimensional surface profiles. The random surface model is employed for a rough electrode\electrolyte interface. In this model the gross geometrical property of an electrochemically active rough surface - the surface structure factor-is related to the average electrode current, current density and concentration. Under short and long time regimes, various morphological features of the rough electrodes, i.e. excess area (related to roughness slope), curvature, correlation length, etc. are related to the (average) current transients. A two-point Pade approximant is used to develop an all time average current expression in terms of partial morphological features of the rough surface. The inverse problem of predicting the surface structure factor from the observed transients is also described. Finally, the effect of surface roughness is studied for specific surface statistics, namely a Gaussian correlation function. It is shown how the surface roughness enhances the overall diffusion-limited charge transfer current.

Sequential Assembly of an Active RNA Polymerase Molecule at the Air-Water Interface

At the heart of understanding cellular processes lies our ability to explore the specific nature of communication between sequential information carrying biopolymers. However, the data extracted from conventional solution phase studies may not reflect the dynamics of communication between recognized partners as they occur in the crowded cellular milieu. We use the principle of immobilization of histidine-tagged biopolymers at a Ni(II)-encoded Langmuir monolayer to study sequence-specific protein-protein interactions in an artificially crowded environment The advantage of this technique lies in increasing the surface density of one of the interacting partners that allows us to study macromolecular interactions in a controlled crowded environment, but without compromising the speed of the reactions. We have taken advantage of this technique to follow the sequential assembly process of the multiprotein complex Escherichia coil RNA polymerase at the interface and also deciphered the role of one of the proteins, omega (omega), in the assembly pathway. Our reconstitution studies indicate that in the absence of molecular chaperones or other cofactors, omega (omega) plays a decisive role in refolding the largest protein beta prime (beta') and its recruitment into the multimeric assembly to reconstitute an active RNA polymerase. It was also observed that the monolayer had the ability to distinguish between sequence-specific and -nonspecific interactions despite the immobilization of one of the biomacromolecules. The technique provides a universal two-dimensional template for studying protein-ligand interactions while mimicking molecular crowding.

On the large-scale diffuse magnetic field of the sun - II. The contribution of active regions

Dikpati and Choudhuri (1993, 1995) developed a model for the poleward migration of the weak diffuse magnetic field on the Sun's surface. This field was identified with the poloidal component produced by the solar dynamo operating at the base of the convection zone, and its evolution was studied by considering the effects of meridional circulation and turbulent diffusion. The earlier model is extended in this paper by incorporating the flux from, the decay of tilted active regions near the solar surface as an additional source of the poloidal field. This extended model can now explain various low-latitude features in the time-latitude diagram of the weak diffuse fields. These low-latitude features could not be accounted for in the earlier model, which was very successful in modeling the behavior at high latitudes. The time-latitude diagrams show that regions of a particular polarity often have 'tongues' of opposite polarity. Such tongues can be produced in the theoretical model by incorporating fluctuations in the source term arising out of the decaying active regions.

Renewable surface electrodes based on dopamine functionalized exfoliated graphite: NADH oxidation and ethanol biosensing

Exfoliated graphite (EG) was modified by covalently attaching dopamine (DA) (3,4-dihydroxyphenethylamine) through amide linkages, using -COOH groups introduced on the EG surface. The modified material was characterized by FT-IR spectroscopy, Xray photoelectron spectroscopy and electrochemical techniques. Composites of DA modified EG dispersed in organically modified silicates were prepared by a sol-get process. Electrodes were fabricated by casting the composites in glass tubes. The sol-gel based electrodes were found to be active for the electrocatalytic oxidation of NADH and biosensing of ethanol in presence of NAD(+) and alcohol dehydrogenase enzyme. The modified composite electrodes were found to be stable for several months. The surface of the electrode could be renewed just by mechanically polishing the electrode using emery sheets. The modified EG was also pressed and restacked in the form of a pellet and the use of this material as a binderless bulk-modified electrode was also demonstrated. The performance of sol-gel derived composite EG electrodes with binderless bulk-modified EG electrodes was compared. (C) 2002 Elsevier Science B.V. All rights reserved.

Self-assembled microtubes and rhodamine 6G functionalized Raman-active gold microrods from 1-hydroxybenzotriazole

1-Hydroxybenzotriazole spontaneously self-assembles to form hollow, linear microtubes initiated by controlled evaporation from water. The tube cavities act as thermo-labile micromoulds for the synthesis of linear gold microrods. Rhodamine 6G-labelled gold microrods, exhibiting surface enhanced resonance Raman activity, have been synthesized using the HOBT microtubes.

Performance Modeling based on Multidimensional Surface Learning for Performance Predictions of Parallel Applications in Non-Dedicated Environments

Modeling the performance behavior of parallel applications to predict the execution times of the applications for larger problem sizes and number of processors has been an active area of research for several years. The existing curve fitting strategies for performance modeling utilize data from experiments that are conducted under uniform loading conditions. Hence the accuracy of these models degrade when the load conditions on the machines and network change. In this paper, we analyze a curve fitting model that attempts to predict execution times for any load conditions that may exist on the systems during application execution. Based on the experiments conducted with the model for a parallel eigenvalue problem, we propose a multi-dimensional curve-fitting model based on rational polynomials for performance predictions of parallel applications in non-dedicated environments. We used the rational polynomial based model to predict execution times for 2 other parallel applications on systems with large load dynamics. In all the cases, the model gave good predictions of execution times with average percentage prediction errors of less than 20%

Design, synthesis and docking studies of new quinoline-3-carbohydrazide derivatives as antitubercular agents

Three new series of 4-hydroxy-8-trifluoromethyl-quinoline derivatives were synthesized through multi step reactions. All the newly synthesized compounds were characterized by spectral and elemental analyses. The structure of 5j was evidenced by X-ray crystallographic study. The newly synthesized title compounds were evaluated for their antimicrobial activities including antimycobacterial activity. Amongst the tested compounds, 5b, 5e, 5h, 5j, 6c and 7c displayed promising antimicrobial activity. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands, 5b, 5e, 5h, 5j and 6c. (C) 2011 Elsevier Masson SAS. All rights reserved.

Dimethyl sulfoxide induced structural transformations and non-monotonic concentration dependence of conformational fluctuation around active site of lysozyme

Experimental studies have observed significant changes in both structure and function of lysozyme (and other proteins) on addition of a small amount of dimethyl sulfoxide (DMSO) in aqueous solution. Our atomistic molecular dynamic simulations of lysozyme in water-DMSO reveal the following sequence of changes on increasing DMSO concentration. (i) At the initial stage (around 5% DMSO concentration) protein's conformational flexibility gets markedly suppressed. From study of radial distribution functions, we attribute this to the preferential solvation of exposed protein hydrophobic residues by the methyl groups of DMSO. (ii) In the next stage (10-15% DMSO concentration range), lysozome partially unfolds accompanied by an increase both in fluctuation and in exposed protein surface area. (iii) Between 15-20% concentration ranges, both conformational fluctuation and solvent accessible protein surface area suddenly decrease again indicating the formation of an intermediate collapse state. These results are in good agreement with near-UV circular dichroism (CD) and fluorescence studies. We explain this apparently surprising behavior in terms of a structural transformation which involves clustering among the methyl groups of DMSO. (iv) Beyond 20% concentration of DMSO, the protein starts its final sojourn towards the unfolding state with further increase in conformational fluctuation and loss in native contacts. Most importantly, analysis of contact map and fluctuation near the active site reveal that both partial unfolding and conformational fluctuations are centered mostly on the hydrophobic core of active site of lysozyme. Our results could offer a general explanation and universal picture of the anomalous behavior of protein structure-function observed in the presence of cosolvents (DMSO, ethanol, tertiary butyl alcohol, dioxane) at their low concentrations. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3694268]