1,720,978 research outputs found

    NEW DIMENSIONS INTO PROTEIN-NUCLEIC ACIDS INTERACTIONS

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    In the late 19th century, scientists microscopically observed the association of proteins with DNA strands. Since then, researchers have used a variety of in vitro and in vivo assays to demonstrate that proteins interact with DNA and RNA to influence the structure and function of the corresponding nucleic acid. Elucidating the roles that protein-nucleic acid complexes play in the regulation of transcription, translation, DNA replication, repair and recombination and RNA processing and translocation continues to revolutionize our understanding of cell biology, normal cell development and the mechanisms of disease. Furthermore, there is the potential for constructing new molecules with excellent functionalities by assembling the very simple elements and components that are the functional subunits of these natural biopolymers. In this work of thesis we attempted making a new step forward a better knowledge of protein-nucleic acid biopolymers, focusing on two complexes of strong interest. One of the important factors for determining the expression of the function is the structure of the biopolymer. Clarification of the relationship between the structure and the function of biopolymer is of crucial importance to the development of methods for constructing tailor-made functional molecules. The first goal of my thesis focalized on the obtainment of a structural model of a well-known protein-DNA complex: Maf DNA binding domain and it DNA target (T-MARE was used in this study) with the aim of outlining a strategy for the obtainment of activity modulators. Both in silico simulations and experimental studies were carried out leading to the definition of a modus-operandi based on a disorder-order transition of the complex which is commendatory for the protein activation. On the other hand, a number of artificial enzymes have been recently constructed by using the molecular design based on structural information, screening methods that utilize libraries or by a combination of these two methods. However, the above mentioned approaches use single proteins or single nucleic acid as the structural unit, and the activity of the constructed artificial enzymes is remarkably lower in many cases, than that of the native enzymes. The construction of functional complexes (rather than a single biopolymer) as scaffold can be considered as one potential solution to these drawbacks. Further in my studies, using the HIV-Rev peptide and RRE (Rev Responsive Element) RNA complex as a scaffold, for which the tridimensional structure was fully characterized, the assemble of ribonucleopeptidic fluorescent sensors was accomplished in a stepwise manner. In this method, a randomized nucleotide sequence was introduced into the RNA subunit of RNP to construct a RNP library on which the in vitro selection method was applied. In the second step, the Rev peptide was modified with the fluorophore without altering the affinity and specificity of the RNP receptor. In the absence of a ligand for RNP, fluorescence emission was effectively quenched in the RNP complex, but recovered upon ligand binding. RNP sensors were thus created, as the ligand-binding event can be monitored by measurement of the fluorescence signals

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Expedient chemical synthesis of 75mer DNA binding domain of MafA : an insight on its binding to insulin enhancer

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    An expedient chemical synthesis of a 75mer peptide corresponding to the DNA binding domain (DBD, 227-301) of the human MafA leucine zipper transcription factor is reported. The application of microwave-assisted solid phase peptide synthesis (MW-SPPS) with a protocol modified respect to the standard one allowed obtaining the desired 75mer peptide in a short time with high quantity and optimal purity. MW-SPPS methodology was thus demonstrated as a valuable alternative to recombinant methods to obtain protein domains. Considering that recent findings suggest an involvement of MafA in the pathogenesis of diabetes mellitus, we also performed circular dichroism studies both on DBD folding and its interaction with MafA recognition element (MARE) on insulin enhancer. From our results, it was evicted that a disorder to order transition occurs after DBD interaction with insulin MARE which is mediated by specific structural elements on the N-terminus of the DBD

    Variations on the Author

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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