Evaluation of bacterial RNase P RNA as a drug target

RNA has gained increasing importance as a therapeutic target. However, so far mRNAs rather than stable cellular RNAs have been considered in such studies. In bacteria, the tRNA-processing enzyme RNase P has a catalytic RNA subunit. Fundamental differences in structure and function between bacterial and eukaryotic RNase P, and its indispensability for cell viability make the bacterial enzyme an attractive drug target candidate. Herein we describe two approaches utilized to evaluate whether the catalytic RNA subunit of bacterial RNase P is amenable to inactivation by antisense-based strategies. In the first approach, we rationally designed RNA hairpin oligonucleotides targeted at the tRNA 3'-CCA binding site (P15 loop region) of bacterial RNase P RNA by attempting to include principles derived from the natural CopA-CopT antisense system. Substantial inactivation of RNase P RNA was observed for Type A RNase P RNA (such as that in Escherichia coli) but not for Type B (as in Mycoplasma hyopneumoniae). Moreover, only an RNA oligonucleotide (Eco 3') complementary to the CCA binding site and its 3' flanking sequences was shown to be an efficient inhibitor. Mutation of Eco 3' and analysis of other natural RNase P RNAs with sequence deviations in the P15 loop region showed that inhibition is due to interaction of Eco 3' with this region and occurs in a highly sequence-specific manner. A DNA version of Eco 3' was a less potent inhibitor. The potential of Eco 3' to form an initial kissing complex with the P15 loop did not prove advantageous. In a second approach, we tested a set of oligonucleotides against E. coli RNase P RNA which were designed by algorithms developed for the selection of suitable mRNA targets. This approach identified the P10/11-J11/12 region of bacterial RNase P RNA as another accessible region. In conclusion, both the P15 loop and P10/11-J11/12 regions of Type A RNase P RNAs seem to be promising antisense target sites since they are easily accessible and sufficiently interspersed with nonhelical sequence elements, and oligonucleotide binding directly interferes with substrate docking to these two regions.     

Variability, covariation, and invariance with respect to coordinate systems in motor control: Reply to Smeets and Louw (2007).

In their comment on the tolerance-noise covariation (TNC) method for decomposing variability by H. Müller and D. Sternad (2003, 2004b), J. B. J. Smeets and S. Louw (see record 2007-01135-017) show that covariation (C), as defined within the TNC method, is not invariant with respect to coordinate transformations and contend that it is, therefore, meaningless. Although the observation is correct, their interpretation is misleading in the following ways: (a) They equate covariation C with the known statistical quantity covariance and noise (N) with standard deviations. The two quantities C and N are conceptually different statistical measures. (b) Dependency on the reference frame is not only a feature of C but of all 3 components. However, such dependency is ubiquitous in motor control. (c) As the frame of reference in biological systems is poorly understood, the TNC method may afford evaluation of different coordinates for control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intercellular Transport of Nanomaterials is Mediated by Membrane Nanotubes In Vivo

So‐called membrane nanotubes are cellular protrusions between cells whose functions include cell communication, environmental sampling, and protein transfer. It has been previously reported that systemically administered carboxyl‐modified quantum dots (cQDs) are rapidly taken up by perivascular macrophages in skeletal muscle of healthy mice. Expanding these studies, it is found, by means of in vivo fluorescence microscopy on the mouse cremaster muscle, rapid uptake of cQDs not only by perivascular macrophages but also by tissue‐resident cells, which are localized more than 100 μm distant from the closest vessel. Confocal microscopy on muscle tissue, immunostained for the membrane dye DiI, reveals the presence of continuous membranous structures between MHC‐II‐positive, F4/80‐positive cells. These structures contain microtubules, components of the cytoskeleton, which clearly colocalize with cQDs. The cQDs are exclusively found inside endosomal vesicles. Most importantly, by using in vivo fluorescence microscopy, this study detected fast (0.8 μm s^?1, mean velocity), bidirectional movement of cQDs in such structures, indicating transport of cQD‐containing vesicles along microtubule tracks by the action of molecular motors. The findings are the first to demonstrate membrane nanotube function in vivo and they suggest a previously unknown route for the distribution of nanomaterials in tissue.     

Developing roles in change processes – A case study from a public sector organisation

Even though change is recognized to be of utmost importance in today´s organisations, there exists no common understanding of change roles. The relationship between change roles and program and project roles seems not to be clear, although many changes are organized by projects. The paper presents a case study of a transformation of a public organisation. In an action research approach together with representatives of the case study company relevant roles for the change were developed and established.     

Influence of water and magnesium ion on the optical properties in various plasticized poly(vinyl butyral) sheets

The study is focused on influences of optical properties change of poly(vinyl butyral) (PVB) sheets determined for safety glass preparing. Optic measurements were evaluated itself and after, the laminated glass was observed. The study deals with a cognizance of causation of the optical properties change in different PVB sheets in dependence on adsorbed water content into the polymer matrix. Results of this work describe the influence of ? OH group content on PVB chain and type and amount of additives adjusting adhesion of PVB towards glass. However, the most important discovery of this work is evaluation of critical water content that leads to haze generation. The evaluation of various types of sheets was performed. At the same time the artificial addition of Mg²⁺ salts of organic acids (with various polarity of the molecule) was evaluated to assess their influence on haze generation. It was found that haze caused by Mg²⁺ salt is possible to eliminate when there is certain water content in PVB. Obtained values and comparisons are very important for PVB sheets industry and for industry dealing with lamination of PVB between glasses. Influence of these factors and comparison of haze generation for various PVB sheets has not been published yet. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Non-invasive ‘through-package’ assessment of the microstructural quality of a model food emulsion by the NMR MOUSE

Recently, NMR has been demonstrated in a truly non-invasive through-package ‘sensor’ mode, also denoted as the MObile Universal Surface Explorer (MOUSE). In this feasibility study, we present a first example where we use the MOUSE sensor for assessment of the microstructural quality of a food material. We have taken model systems consisting of protein-stabilized oil-in-water emulsions, where an important microstructural quality parameter is water exudation (WE). In order to establish a sound relation between MOUSE signals and WE, it was necessary to deploy multivariate calibration techniques. It was found that the performance of the MOUSE is comparable to that of conventional benchtop NMR. Thus it was demonstrated that the NMR MOUSE presents a good option for non-invasive assessment of microstructural quality parameters, e.g. in manufacturing and in the supply chain.     

Quantum Key Distribution: from Principles to Practicalities

We review the main protocols for key distribution based on principles of quantum mechanics, describing the general underlying ideas, discussing implementation requirements and pointing out directions of current experiments. The issue of security is addressed both from a principal and real-life point of view. Received: October 15, 1998; revised version: June 8, 1999     

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