Detection of Alzheimer's tau protein using localised surface plasmon resonance-based immunochip

In this study, we present the detection of tau protein, at room temperature, using a multi-spot localised surface plasmon resonance (LSPR)-based immunochip. To the best of our knowledge, this is the first report of an immunochip for tau protein. The detection method includes fabrication of a gold-capped nanoparticle LSPR chip, formation and functionalisation of a self-assembled monolayer (SAM), immobilisation of a suitable linker, effective blocking of non-specific adsorption, immobilisation of a monoclonal anti-tau antibody (tau-mAb), and finally, the optimum conditions for the immuno-reaction between tau-mAb and the antigen were determined. The method has a high performance, enables detection of tau at 10pg/mL, lower than the cut-off value of 195pg/mL (for AD) for tau protein in cerebral spinal fluid (CSF). Further, we demonstrated selectivity of the technique by showing that the introduction of bovine serum albumin (BSA), perhaps the most abundant protein component in serum and CSF, does not interfere with the detection of tau. This method also offers a potential platform for studying tau interactions with other proteins and/or potential drug candidates and could also be easily adapted for detecting phosphorylated tau and other AD biomarkers.     

Effects of pH, sample size, and solvent partitioning on recovery of soluble phenolic acids and isoflavonoids in leaves and stems of red clover (Trifolium pratense cv. Kenland)

Several extraction parameters were tested to determine optimal conditions for extracting phenolics from leaves and stems of red clover (Trifolium pratense L. cv. Kenland), with the goal of using extracts in bioassays and in assessment of phenolic profiles. HPLC-UV profiles were compared before and after partitioning a methanolic extract of soluble phenolics with ethyl acetate-ethyl ether (1:1, v/v). The effect of extract pH on the partitioning of phenolics into the ethyl acetate-ethyl ether (EtOAc-Et2O) phase was evaluated, and several tissue weights were extracted to determine a minimum amount that could be extracted without loss of information. HPLC profiles of soluble phenolics were similar in the methanolic extracts and the partitioned EtOAc-Et2O extracts. However, recoveries in unpartitioned extracts were 2- to 4-fold greater than in the acidified, partitioned extracts. Also, recovery was considerably affected by the pH to which extracts were adjusted prior to partitioning. In extracts acidified to pH 2, recoveries were 2- to 7-fold higher than in extracts partitioned at pH 6. In extracts prepared from 250, 120, or 60 mg of tissue, peak areas of methanolic extracts were directly proportional to the amount of tissue extracted.     

Asymmetric oxidation of some 1,3-dithianes in presence of chiral titanium complexes

Various 2-substituted 1,3-dithianes have been oxidized to the corresponding 1-oxides by cumene hydroperoxide in presence of a titanium complex (Ti(O-i-Pr)₄/(+)-DET/H₂O = 1/2/1) used in stoichiometric or lesser amounts. Enantioselectivity of up to 80% and excellent diastereoselectivity were achieved by a careful control of experimental conditions. The reaction temperature was found to be an important parameter. The relative stereochemistries of the new substituted monosulfoxides were determined by NMR spectroscopy.     

Oxidative dimerization of alcohols in the presence of nitroxyl radical–iodine catalytic system

Pyridine catalyzes oxidation of alcohols with 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl–iodine catalytic system at room temperature. Symmetric esters are formed in good yields.     

Circumventing air bubbles in microfluidic systems and quantitative continuous-flow PCR applications

Polymerase chain reaction (PCR) is an essential part of research based on genomics or cell analysis. The development of a microfluidic device that would be suitable for high-temperature-based reactions therefore becomes an important contribution towards the integration of micro-total analysis systems (μTAS). However, problems associated with the generation of air bubbles in the microchannels before the introduction of the assay liquid, which we call the “initial start-up” in this study, made the flow irregular and unstable. In this report, we have tried to address these problems by adapting a novel liquid-flow method for high-temperature-based reactions. A PDMS-based microfluidic device was fabricated by soft-lithography techniques and placed on a cartridge heater. The generation of the air bubbles was prevented by introducing the fluorinated oil, an inert and highly viscous liquid, as the cap just before the introduction of the sample solutions into the microchannels. The technique was applied for continuous-flow PCR, which could perform PCR on-chip in a microfluidic system. For the evaluation of practical accuracy, plasmid DNA that serves as a reference molecule for the quantification of genetically modified (GM) maize was used as the template DNA for continuous-flow PCR. After PCR, the products were collected in a vial and analyzed by gel electrophoresis to confirm the accuracy of the results. Additionally, quantitative continuous-flow PCR was performed using TaqMan technology on our PCR device. A laser detection system was also used for the quantitative PCR method. We observed a linear relationship between the threshold cycle (Ct) and the initial DNA concentration. These results showed that it would be possible to quantify the initial copies of the template DNA on our microfluidic device. Accurate quantitative DNA analysis in microfluidic systems is required for the integration of PCR with μTAS, thus we anticipate that our device would have promising potential for applications in a wide range of research.     

Mitochondrial targeting of selective electron scavengers: synthesis and biological analysis of hemigramicidin-TEMPO conjugates

Synthetic hemigramicidin S-peptidyl TEMPO conjugates are effectively delivered into cells and mitochondria, where they act as electron scavengers and exert protection against apoptosis. Our delivery approach is based on the use of specific structural signaling features recognizable by cells as mitochondria targeting sequences and offers considerable therapeutic anti-apoptotic potential.     

An algorithm for self-consistent field MO LCAO computations on conjugated systems with allowance for configuration interaction

The Pariser-Parr-Pople method is described briefly. An algorithm is presented for quantum-mechanical computation of molecular structures. A program for the BESM-2M computer is presented.     

Anomalous resistivity of lithium at high dynamic pressure

The experimental investigation of lithium compressed by multiple shock waves to a pressure of 210 GPa demonstrates the abnormal dependence of electrical resistivity. Contrary to normal metal behavior, the resistivity monotonically increases in the pressure range 30–150 GPa by more than 15 times from a typical metallic value at ambient conditions and reverts to a metallic value at a pressure higher than 160–210 GPa. The obtained results demonstrate the anomalous resistivity of lithium both in solid and in liquid states.     

Low-temperature thermal conductivity of tellurium-doped bismuth

Phonon thermal conductivities κ₂₂ (?T ‖ C1) and κ₃₃ (? T ‖ C₃) of tellurium-doped bismuth with an electron concentration in the range 1.8 × 10¹⁹ ≤ n_L ≤ 1.4 × 10²⁰ cm^?3 were studied in the temperature interval 2 < T < 300 K. The temperature dependence of the phonon thermal conductivity obtained on doped bismuth samples of both orientations exhibits two maxima, one at a low temperature and the other at a high temperature. The effect of various phonon relaxation mechanisms on the dependence of both phonon thermal conductivity maxima on temperature, impurity concentration, and electron density is studied.