Frontal midline theta rhythm (Fm theta) is a distinct theta activity of EEG in the frontal midline area that appears during concentrated performance of mental tasks in normal subjects and reflects focused attentional processing. To tomographically visualize the source current density distributions of Fm theta, we recorded Fm theta by using a 64-channel whole-head MEG system from four healthy subjects, and applied a new analysis method, synthetic aperture magnetometry (SAM), an adaptive beam forming method. Fm theta was observed in the MEG signals over the bilateral frontal regions. SAM analysis showed bilateral medial prefrontal cortices, including anterior cingulate cortex, as the source of Fm theta. This result suggests that focused attention is mainly related to medial prefrontal cortex.
DNA triplex formation has been studied as a potential strategy for regulation of gene expression. The triplex is, however, unstable under physiological conditions, so that an effective stabilizer for the triplex formation is needed. Here is shown a novel strategy to stabilize the triplex based on the molecular design of a comb-type polycation. Linear polycations, such as poly(L-lysine) and poly(L-arginine), thermally stabilize DNA duplexes (and triplexes). The complexes between DNA and the polycation are irreversible and are liable to precipitate out of aqueous media. The irreversibility and phase separating properties of the complex impede association of single-stranded (ss) DNAs in the complex to form duplexes and triplexes. A comb-type polycation consisting of a poly(L-lysine) backbone and grafted chains of hydrophilic polymers was prepared. The comb-type copolymers increased solubility of their complex with DNA and suppressed conformational changes of DNA. Thermal melting curve analyses revealed that the comb-type copolymer markedly stabilized DNA triplexes and did not disturb ssDNAs in forming duplexes and triplexes. Reversible and one-step melting/reassociation transitions of poly(dA).2poly(dT) triplex were shown in the pressure of the copolymers. The stabilizing effect of the copolymer was larger than that of spermine, a polyamine considered effective in stabilizing triplexes. These results indicated that molecular design of polycations with a comb-type structure is a novel strategy to create efficient triplex stabilizers. Such comb-type copolymer consisting of various types of polycation backbones and hydrophilic graft chains may have many applications in which specific and precise interactions of polynucleotides are involved.
This study revealed that the ABC phenomenon is induced by PEG-modified PLA-nanoparticles. We consider that NP-L33s may be useful clinically for the sustained-release and targeted delivery of PGE(1).
The polyionic interaction between DNA and polycations grafted with hydrophilic dextran side chains was evaluated. The comb-type copolymers, poly(L-lysine)-graft-dextran, were successfully prepared by employing a reductive amination reaction between epsilon-amino groups of poly(L-lysine) (PLL) and the reductive ends of dextran (Dex). A coupling efficacy on the order of 70% was obtained regardless of intrinsic philicities of the solvents used, either aqueous buffer or DMSO. The resulting graft copolymers, which varied in the degree of grafting and the length of hydrophilic side chains, formed a soluble complex with DNA. They also affected the melting behavior of double-stranded DNA (dsDNA) in different ways. Copolymers having a high degree of grafting thermally stabilized dsDNA without affecting its reversible transition between single-stranded and double-stranded forms. However, copolymers with a low degree of grafting or with a high degree of grafting of short dextran chains impeded the reversibility of this transition. Furthermore, highly grafted copolymers also accelerated the hybridization of DNA strands in a low-ionic strength medium. It is of particular note that these copolymers scarcely altered circular dichroismic signals of dsDNA even when the copolymers were added in excess. This suggested that the copolymer interacted with dsDNA without affecting its native structure or physicochemical properties. Finally, the copolymer even formed a stable complex with a short oligonucleotide (20 bases). We, therefore, concluded that, by regulating the degree of grafting and the molecular weight of grafted side chains, it would be possible to design novel different graft copolymers capable of acting as carriers of functional genes to target cells or tissue.
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