1,720,971 research outputs found
Mimicking the action of ribonucleases : studies on RNase A and design of PNA based artificial enzymes
No full textA 3’-deoxy-3’-C-methylenephosphonate modified diribonucleotide is highly resistant to degradation by spleen phosphodiesterase and not cleaved at all by snake venom phosphodiesterase. Despite that both the vicinal 2-hydroxy nucleophile and the 5’-oxyanion leaving group are intact, the 3’-methylenephosponate RNA modification is also highly resistant towards the action of RNase A.Several different approaches were explored for conjugation of oligoethers to PNA with internally or N-terminal placed diaminopropionic acid residues. Using a post PNA-assembly procedures oligoether attachment to both N-terminal and sidechain amino groups was achieved. Use of a new oligoether functionalized amino acid allows inclusion of oligoether conjugates during on-line machine assisted synthesis, allowing combination of methods for attachment of different oligoethers and co-conjugation of neocuproine cleaver.We have previously shown that PNA-neocuproine conjugates can act as artificial RNA restriction enzymes (PNAzyme). In the present study we have additionally conjugated the PNA with different entities and also constructed systems where the PNA is designed to clamp the target RNA forming a triplex. Some conjugations are detrimental for the activity while most are silent which means that conjugation can be done to alter physical properties without losing activity. Conjugation with a single oligoether close to the neocuproine does enhance the rate almost two folds compared to the system without the oligoether. The systems designed to clamp the RNA target by forming a triplex are effective if the clamping part is not too long. Changing the direction of a closing base pair, from a GC to a CG pair, enhances the rate of cleavage with a clamping PNAzyme and without compromising the selectivity, leading to the so far most efficient artificial nuclease reported.Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are effective site-specific metal-free RNA cleavers. Here we investigate conjugates with peptide nucleic acids (PNA). In a first study we show that RNA degradation occurs with similar rates and substrate specificities as in experiments with DNA conjugates. In a second study we show that tris(2-aminobenzimidazole) based artificial nucleases cleave RNA substrates, which form a bulge upon binding to the PNA, with turnover of substrate and a cleavage rate that is also dependent on the bulge sequence. Two methods of analysis for the kinetics, based on IE-HPLC separation of oligonucleotide fragments and analysis of Cy5-labelled oligonucleotide fragments by denaturating PAGE on a DNA sequencer respectively are also compared.To be able to target microRNAs also at stages where these are in a double stranded or hairpin form we have looked at BisPNA designed to clamp the target and give sufficient affinity to allow for strand invasion. We show that BisPNA complexes are more stable with RNA than with DNA. In addition, 24-mer BisPNA (AntimiR) constructs form complexes with a hairpin RNA that is a model of the microRNA miR-376b, suggesting that PNA-clamping may be an effective way of targeting microRNAs.List of scientific papersI. Alice Ghidini, Charlotte Ander, Anna Winqvist and Roger Strömberg. An RNA modification with remarkable resistance to RNase A. Chem Commun. 2013, 49, 9036. https://doi.org/10.1039/c3cc44621b II. Alice Ghidini, Peter Steunenberg, Merita Murtola and Roger Strömberg. Synthesis of PNA Oligoether Conjugates. Molecules. 2014, 19, 3135-3148. https://doi.org/10.3390/molecules19033135 III. Friederike Danneberg, Alice Ghidini, Plamena Dogandzhiyski, Elisabeth Kalden, Roger Strömberg and Michael W. Göbel. Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole). Beilstein J Org Chem. 2015, 11, 493–498. https://doi.org/10.3762/bjoc.11.55 IV. Alice Ghidini, Helen Bergquist, Tanel Punga, Rula Zain and Roger Strömberg. Clamping of RNA with PNA enables targeting of microRNA. [Manuscript]V. Alice Ghidini, Merita Murtola and Roger Strömberg. Influence of conjugation and other structural changes on the activity of Cu2+ based PNAzymes. [Manuscript]VI. Plamena Dogandzhiyski, Alice Ghidini, Friederike Danneberg, Roger Strömberg, Michael W. Göbel. Studies on tris(2-aminobenzimidazole)-PNA based artificial nucleases and comparison of two analytical techniques. [Manuscript]</p
Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA2DNA triplexes
No full textPyrene derivatives can be incorporated into nucleic acid analogs in order to obtain switchable probes or supramolecular architectures. In this paper, peptide nucleic acids (PNAs) containing 1 to 3 1-pyreneacetic acid units (PNA1–6) with a sequence with prevalence of pyrimidine bases, complementary to cystic fibrosis W1282X point mutation were synthesized. These compounds showed sequence-selective switch-on of pyrene excimer emission in the presence of target DNA, due to PNA2DNA triplex formation, with stability depending on the number and positioning of the pyrene units along the chain. An increase in triplex stability and a very high mismatch-selectivity, derived from combined stacking and base-pairing interactions, were found for PNA2, bearing two distant pyrene units
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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