New insight into interference-free and highly sensitive dopamine electroanalysis.

Early diagnosis of Parkinson's disease and hyperprolactinemia based on electrochemical dopamine (DA) sensing appears as an efficient and promising practical diagnostic method. However, the coexistence of DA in real samples with ascorbic acid (AA) and uric acid (UA), which oxidize at potentials close to its own, prevents the accurate electrochemical DA sensing and therefore, hinders the effective diagnosis of these diseases. In this work, we successfully combined the electrostatic proprieties of GO, the electron transfer properties of an AuNPs@MWCNTs nanocomposite and the ability of thiol group of the amino acid l-cysteine to react chemically with carbonyl groups of UA, to develop a novel approach that enabled complete suppression of interference from AA and UA and hence, accurate DA electroanalysis in the conditions close to those of human blood serum. The chemical reaction between l-cysteine and UA was evidenced by monitoring the DPV responses of UA under different conditions. XRD, Raman spectroscopy, XPS and FE-SEM revealed the successful synthesis of GO and AuNPs@MWCNTs. The study of the electrode material (GO-AuNPs@MWCNTs) morphology via FE-SEM and HR-TEM showed that AuNPs@MWCNTs are distributed throughout the exfoliated GO layers. The fabricated sensor was calibrated in the concentration range of 0.5-5 µM, in the presence of the highest blood concentrations of AA and UA for healthy individuals. A linear relationship was observed and the LOD was found to be 1.31 nM (S/N = 3). Furthermore, the sensor showed good electron transfer kinetics, good repeatability and reproducibility, satisfactory long-term stability, and recoveries in human blood serum.

Effect of Dispersoid on Sulfonium Ionic Liquid Based Gel Polymer Electrolyte for Lithium Secondary Battery.

The present study emphases on the effect of toting of TiO2 filler on the electrochemical enactment of polymer electrolyte containing PVdF-co-HFP(30) + SEt3TFSI(10) + EC/PC(60) + TiO2(x) wt% (Poly (vinylidene fluoride-co-hexafluoropropylene + Triethylsulfoniumbis(trifluoromethylsulfonyl)imide + Ethylene carbonate/Propylene carbonate (1:1 ratio) + Titanium dioxide) for lithium battery applications. Composite electrolytes with different weight percentages of TiO2 were prepared and characterized by different surface analytical, thermal and electrochemical techniques. With gradual increase of the amount of TiO2 upto 6 wt%, broadening of the prominent peak has been noted, suggesting a decrease in the degree of crystallinity upon the addition of TiO2, as revealed by X-ray diffraction (XRD). Raman and FT-IR studies confirm the presence of various functional groups, present in the matrix. The electrolyte with TiO2 (6 wt%) has maximum stability of 460 °C, as confirmed by thermal analysis. Conductivity of the composite polymer electrolytes increases upto 6 wt% of TiO2 (3.42 × 10-3 S/cm at 303 K) and further addition, causes a dip down in conductivity, indicating an improvement in the ionic conductivity and thermal stability with the incorporation of TiO2 filler. Surface morphologic images show the presence of surface and cavity in the polymer matrix, filled with the filler uniformly. Voltammetric studies confirm the electrochemical stability of films upto 4.62 V. Coin cell containing Li anode and LiFePO4 cathode along with polymer electrolyte/6 wt% TiO2 filler, delivers a first discharge capacity of 145 mAh/g with the working voltage of 3.4 V.

Molecular modeling and structural analysis of nAChR variants uncovers the mechanism of resistance to snake toxins.

Nicotinic acetylcholine receptors (nAChRs) are neuromuscular proteins responsible for muscle contraction upon binding with chemical stimulant acetylcholine (ACh). The α-neurotoxins of snake mimic the structure of ACh and attacks nAChRs, which block the flow of ACh and leads to numbness and paralysis. The toxin-binding site of alpha subunit in the nAChRs is highly conserved throughout chordate lineages with few exceptions in resistance organisms. In this study, we have analyzed the sequence and structures of toxin-binding/resistant nAChRs and their interaction stability with toxins through molecular docking and molecular dynamics simulation (MDS). We have reported the potential glycosylation residues within the toxin-binding cleft adding sugar moieties through N-linked glycosylation in resistant organisms. Residue variations at key positions alter the secondary structure of binding cleft, which might interfere with toxin binding and it could be one of the possible explanations for the resistance to snake venoms. Analysis of nAChR-α-neurotoxin complexes has confirmed the key interacting residues. In addition, drastic variation in the binding stability of Mongoose nAChR-α-Bungarotoxin (α-BTX) and human nAChR-α-BTX complexes were found at specific phase of MDS. Our findings suggest that specific mutations in the binding site of toxin are potentially preventing the formation of stable complex of receptor-toxin, which might lead to mechanism of resistance. This in silico study on the binding cleft of nAChR and the findings of interacting residues will assist in designing potential inhibitors as therapeutic targets.

A three-dimensional chemical phase pharmacophore mapping, QSAR modelling and electronic feature analysis of benzofuran salicylic acid derivatives as LYP inhibitors.

Lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, has a critical negative regulatory role in T-cell antigen receptor (TCR) and emerged as a promising drug target for human autoimmune diseases. A five-point pharmacophore with two hydrogen bond acceptors, one hydrogen bond donor and two aromatic ring features was generated for a series of benzofuran salicylic acid derivatives as LYP inhibitors in order to elucidate their anti-autoimmune activity. The generated pharmacophore yielded a significant 3D-QSAR model with r(2) of 0.9146 for a training set of 27 compounds. The model also showed excellent predictive power with Q(2) of 0.7068 for a test set of eight compounds. The investigation of the 3D-QSAR model has revealed the structural insights which could lead to more potent analogues. The most active and inactive compounds were further subjected to electronic structure analysis using density functional theory (DFT) at B3LYP/3-21(∗)G level to support the 3D-QSAR predictions. The results obtained from this study are expected to be useful in the proficient design and development of benzofuran salicylic acid derivatives as inhibitors of LYP.

Ciprofloxacin-protected gold nanoparticles.

The antibacterial drug ciprofloxacin (cfH) has been used to protect gold nanoparticles of two different mean diameters, 4 and 20 nm. The protection is complete with about 65 and 585 cfH molecules covering 4 and 15 nm particles, respectively. The nature of binding has been investigated by several analytical techniques. The nitrogen atom of the NH moiety of piperazine group binds on the gold surface, as revealed by voltammetric and spectroscopic studies. The cfH-adsorbed particles are stable in the dry state as well as at room temperature, and as a result, redispersion is possible. The rate of release of the drug molecule from the nanoparticles is more in the basic medium than in pure water, and the kinetics depend on the size of the particle; faster desorption is seen in smaller particles. The bound cfH is fluorescent, and this property could be used in biological investigations. This study shows that metal nanoparticles could be useful carriers for cfH and fluoroquinolone molecules. Most of the bound molecules could be released over an extended period of time.

Nucleotide sequence of DR-B exon of major histocompatibility complex from an Indian zebu cattle breed.

The Indian cattle is known to be more tolerant to tropical infections than the European cattle. In order to verify the genetic basis of this variation, the DR B exon-2 of the major histocompatibility locus, known for coding the antigen recognition site, from the Hallikar breed of Indian cattle was amplified by PCR, cloned and sequenced. Comparison of this sequence with the information available on taurus cattle brought out six unique nucleotide changes and three amino acid changes. The amino acid positions were at 17, 72 and 87. A major variable region was observed at amino acid position 85 to 87 from all the alleles so far reported for the bovine locus.