Search

Abstract A novel antibacterial immunostimulant using Platinum nanoparticles (PtNPs) and lectin from Metapenaeus dobsoni (Md-Lec) was developed. The Md-Lec and PtNPs (Pt-lec) hybrid formed through non-covalent interaction exhibits antimicrobial activity against fish specific pathogens by affecting membrane integrity and producing excess reactive oxygen species. The therapeutic efficacy of Pt-lec was demonstrated through rescuing Aeromonas hydrophila infected Nile Tilapia. Pt-lec prevents the infection spreading and reduces the bacterial bioburden in less than 12 h, and as a result of this the fish were restored to normalcy. To assess immunostimulation, we studied the expression of three different immune related genes, namely LEC, Myd88 and COX-2 in the gills, liver, spleen and kidney of fish under various experimental conditions. Our results showed that Pt-lec treatment appeared to be better when compared to lectin alone in enhancing the expression of Myd88 and COX-2, but LEC was not as expected. These results suggest that Pt-lec has the ability to protect Nile Tilapia against bacterial infection by restricting bacterial bioburden through their direct effects on the bacterial membrane and indirectly through their effects on host immune-related gene expression. This hybrid could have potential “green” application in fish farming in rescuing infected animals when compared to widely and unregulated antibiotics.

Abstract: Folding of polytopic transmembrane proteins involves interactions of individual transmembrane helices, and multiple TM helix–helix interactions need to be controlled and aligned to result in the final TM protein structure. While defined interaction motifs, such as the GxxxG motif, might be critically involved in transmembrane helix–helix interactions, the sequence context as well as lipid bilayer properties significantly modulate the strength of a sequence specific transmembrane helix–helix interaction. Structures of 11 transmembrane helix dimers have been described today, and the influence of the sequence context as well as of the detergent and lipid environment on a sequence specific dimerization is discussed in light of the available structural information. This article is part of a Special Issue entitled: Protein Folding in Membranes. [Copyright &y& Elsevier]

A new pyrene-appended polypyridine ligand, wherein the 1,10-phenanthroline (phen) and the photoactive pyrene chromophore is connected via a C N bond; N-[1,10]phenanthrolin-5-yl-pyrenylmethanimine (ppym) and its complex [Ru(phen) 2 ( ppym ) ] 2+ was synthesized. Characterization of the ligand and the complex was investigated through elemental analysis, UV-vis, IR, 1 H NMR, MALDI-TOF mass and cyclic voltammetry techniques. The change in dipole moment of the ground and the excited state of the chromophores with the different solvent polarity was examined. The dual emission (Excimer) characteristics observed for ligand ppym has been probed by detailed photophysical studies involving variable concentration, excitation wavelength and solvent experiments and also transition metal ion induced quenching data. 3 MLCT emission was observed for [Ru(phen) 2 ( ppym ) ] 2+ . Absorption, emission, thermal melting and viscosity studies reveal that [Ru(phen) 2 ( ppym ) ] 2+ bind to CT DNA avidly and that ruthenium-bound ppym intercalate inside the base sets of the duplex. Also, the DNA photonicking activity (pBR 322 DNA, λ exc  = 450 nm) of [Ru(phen) 2 ( ppym ) ] 2+ is almost four times higher than [Ru(phen) 3 ] 2+ . Through inhibitor studies, we found that reactive oxygen species play a major role in the photo cleavage of [Ru(phen) 2 ( ppym ) ] 2+ . The cytotoxicity of the complex was tested in Human cancer cell line (ZR-75-30) by MTT assay. In addition, modeling studies scaffold the intercalative binding to the d(CGCAATTGCG) 2 sequence. [ABSTRACT FROM AUTHOR]

In any therapeutic modality the usage of drug in high doses often leads to serious side-effects. Herein, we demonstrated a method to enhance the antibacterial efficacy of CuS NPs at lower concentration through interacting with jackfruit seed lectin, jacalin. Fluorescence quenching studies revealed that jacalin form complex with CuS NPs and the association constant was 1.91 × 10 4  M −1 . Upon complex with jacalin, the bacterial minimum inhibitory concentration (MIC) of CuS NPs drastically decreases from 12.5 μM to 0.78 μM. The addition of jacalin specific sugar, galactose to jacalin-CuS NPs complex (JCuS NPs) reverses the MIC from 0.78 μM to 25 μM. Mechanistic study suggests that JCuS NPs kills bacteria in part by reactive oxygen species and membrane damage, but galactose prevents the action of JCuS NPs at 0.78 μM. JCuS NPs successfully reduce (14 fold) A. hydrophila colonization in an infected zerbra fish and rescue them completely from the infection, but galJCuS NPs and CuS NPs were ineffective at 0.78 μM. Collectively, our studies demonstrates that the enhance antibacterial activity of JCuS NPs is likely due to the interaction between the galactose binding site of jacalin and the bacterial strains, as a result NPs are targeted and delivered sufficiently. [ABSTRACT FROM AUTHOR]

In this paper, the application of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) synthesized using a biomimetic lipid, N-myristoyltaurine (N14T) was evaluated in common fields. The catalytic effectiveness of AgNPs and AuNPs was studied in the popular nanocatalyst reaction, nitroaromatic reduction, and dye degradation. Both NPs display catalytic activity in the nitroaromatic compound and organic dyes reduction reaction involving sodium borohydride and the rate constant is estimated as 10−3 s−1. Strikingly, the reaction initiation time (t 0) and completion time (t c) differ significantly between AgNPs and AuNPs. Analyzing the reaction kinetic profile revealed that the reaction carried out with AuNPs showed a shorter t 0 and t c , suggesting a better catalyst than AgNPs. In addition, the efficiency of the NPs was examined in Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli , Pseudomonas aeruginosa). In difference to the catalytic study, AuNPs display poor antibacterial activity. Whereas AgNPs kill the tested bacteria at 250 μM via disturbing bacterial membrane integrity and produce excess reactive oxygen species. The toxicology study carried out with zebrafish animal model reveals that both AgNPs and AuNPs are non-toxic. The findings suggest that each nanomaterial possesses unique physicochemical properties irrespective of stabilization with the same molecules. •Both NPs display catalytic activity in the nitroaromatic compound and organic dyes reduction •the reaction initiation time (t0) and completion time (tc) differ significantly between AgNPs and AuNPs. • the reaction carried out with AuNPs showed a shorter t0 and tc, suggesting a better catalyst than AgNPs. •The toxicology study carried out with zebrafish animal model reveals that both AgNPs and AuNPs are non-toxic. [ABSTRACT FROM AUTHOR]

Bacterial resistance is a major clinical problem, which is compounded by both a lack of new antibiotics and emergence of multi- and extremely-drug resistant microbes. In this context, non-toxic nanoparticles could play an important role in conferring protection against bacterial infections and in this study we have made an attempt to show the usefulness of jacalin capped platinum nanoparticles in protecting zebrafish against multiple infections with Aeromonas hydrophila. Our results also indicate that use of nanoparticles promotes adaptive immune response against the pathogen, so much so that zebrafish is able to survive repetitive infection even after twenty one days of being treated with jacalin-capped platinum nanoparticles. This is significant given that platinum salt is not antibacterial and jacalin is non-immunogenic. Our study for the first time reveals a novel mechanism of action of nanoparticles, which could form an alternate antibacterial strategy with minimal bacterial resistance.

Detergents might affect membrane protein structures by promoting intramolecular interactions that are different from those found in native membrane bilayers, and fine-tuning detergent properties can be crucial for obtaining structural information of intact and functional transmembrane proteins. To systematically investigate the influence of the detergent concentration and acyl-chain length on the stability of a transmembrane protein structure, the stability of the human glycophorin A transmembrane helix dimer has been analyzed in lyso-phosphatidylcholine micelles of different acyl-chain length. While our results indicate that the transmembrane protein is destabilized in detergents with increasing chain-length, the diameter of the hydrophobic micelle core was found to be less crucial. Thus, hydrophobic mismatch appears to be less important in detergent micelles than in lipid bilayers and individual detergent molecules appear to be able to stretch within a micelle to match the hydrophobic thickness of the peptide. However, the stability of the GpA TM helix dimer linearly depends on the aggregation number of the lyso-PC detergents, indicating that not only is the chemistry of the detergent headgroup and acyl-chain region central for classifying a detergent as harsh or mild, but the detergent aggregation number might also be important., (Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

gamma-Secretase is critically involved in the Notch pathway and in Alzheimer's disease. The four subunits of gamma-secretase assemble in the endoplasmic reticulum (ER) and unassembled subunits are retained/retrieved to the ER by specific signals. We here describe a novel ER-retention/retrieval signal in the transmembrane domain (TMD) 4 of presenilin 1, a subunit of gamma-secretase. TMD4 also is essential for complex formation, conferring a dual role for this domain. Likewise, TMD1 of Pen2 is bifunctional as well. It carries an ER-retention/retrieval signal and is important for complex assembly by binding to TMD4. The two TMDs directly interact with each other and mask their respective ER-retention/retrieval signals, allowing surface transport of reporter proteins. Our data suggest a model how assembly of Pen2 into the nascent gamma-secretase complex could mask TMD-based ER-retention/retrieval signals to allow plasma membrane transport of fully assembled gamma-secretase.