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Micro RNAs (miRNA) regulate gene expression by hybridization and recruitment of multi-protein complexes to complementary mRNA target sequences. miRNA function can transiently be antagonized by antagomirs—chemically modified oligonucleotides complementary to individual miRNAs. Here, we describe the induction of stable loss-of-function phenotypes for specific miRNAs by lentivirus-mediated antagomir expression. Lentivirally expressed antagomirs are transcribed from a H1-promoter located within the lentiviral 3′LTR and were directed against miRNAs encoded on the polycistronic miR17-92 transcript. Functional silencing of miR-18a, miR-19b and miR-20a by the corresponding antagomirs specifically relieves miRNA-mediated reporter gene repression. Inhibition of miRNA function correlates to reduction of ‘miRNA’ amplification by miRNA-specific quantitative RT-PCR. Furthermore, protein expression of E2F-1, a known miR-20 target, is enhanced by lentivirally expressed anti-miR-20 antagomirs in a dose-dependent manner, whereas over-expression of miR-20a reduces E2F-1 levels. Finally, combined over-expression of specific miRNAs and antagomirs reveals individual and complementary functions of miR-18a and miR-20a and demonstrates specific miRNA impact on cell proliferation in a cell culture model.

Peripheral nerve stimulation (PNS) caused by time-varying magnetic fields has been studied both theoretically and experimentally. A human volunteer study performed on three different body-size gradient coils and one head-size gradient coil is presented in this work. The experimental results were used to generate average PNS threshold parameters for the tested gradient systems. It was found that the average stimulation threshold increases while gradient-region-of-uniformity size decreases. In addition, linear relationships between PNS parameters and diameter of homogeneous gradient spherical volume (DSV) were discovered: SR min and ⌬G min both vary inverse linearly with DSV. More importantly, the chronaxie value was found to vary inversely linearly with the DSV. This finding indicates that, contrary to the general understanding, the parameter "chronaxie" in the commonly accepted simple stimulation models cannot be considered to be a single-value, nerve-specific constant. A modified linear model for gradient-induced PNS based on these results was developed, which may permit, for the first time, Key words: gradient coils; peripheral nerve stimulation (PNS); diameter of homogeneous spherical volume (DSV); chronaxieHigh-strength, high-slew-rate gradient coils are desired in modern MRI for better image quality and faster imaging speed. However, rapidly time-varying magnetic fields produced by gradient coils induce electric fields in tissue, which can cause peripheral nerve stimulation (PNS). This significantly limits our ability to take full advantage of these high-performance gradient systems. Despite considerable research in this area in recent years, the relationship between PNS thresholds and gradient coil linear region dimensions or gradient performance parameters is still not well understood. In this study, we investigated this relationship.The fundamental law of electrostimulation is written as (1)where E stim is the threshold electric field to cause stimulation, is the interval over which this electric field is applied, E r is the electric field rheobase, and c is the chronaxie. The rheobase E r is defined as the minimum electric field to produce stimulation, and chronaxie c is defined as the stimulus duration for which the threshold E stim is twice the value of the rheobase E r . Currently accepted gradient-induced PNS models utilize these two parameters (rheobase E r and chronaxie c ) to define PNS threshold curves. It has been assumed that these two parameters are functions only of underlying nerve properties. Recently, Chronik and Rutt (2) reported different rheobase and chronaxie values for a head-size coil and a body coil, and attributed these differences to different nerve sensitivities in the head and body. On the other hand, various studies have reported different values of rheobase and chronaxie even within one class of gradient coils, such as whole-body coils (1-8). We hypothesized, therefore, that these "nerve-specific" PNS model parameters are actually dependent in a predictable way on gradient c...

Summary NCAM is ubiquitylated, endocytosed and recycled in neurons

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