1,721,051 research outputs found
PERSONALIZED MEDICINE FIGHTING NONSENSE DISEASES: EXPLORATION OF NV MOLECULES MECHANISM OF ACTION IN PURE-LITE SYSTEM AND THEIR READTHROUGH ACTIVITY IN CHOROIDEREMIA NONSENSE MODEL
No full textPrecision medicine represents a new approach in genetic medicine for treating a patient's mutation profile. Nonsense mutations cause 11% of inherited genetic diseases, including Choroideremia (CHM), Cystic fibrosis (CF), Duchenne Muscular Dystrophy (DMD), and some Cancers. Choroideremia is an X-linked disease associated with many retinal disorders. This retinal dystrophy causes the progressive degeneration of the choriocapillaris, photoreceptors, and retinal pigment epithelium. The CHM gene codifies for a 95 kDa, known as rab escort protein 1 (Rep1), involved in the intracellular trafficking and prenylation of polypeptides, a post-translational modification fundamental for the correct functionality of specific proteins. Nonsense mutations represent about 34% of mutations in the CHM gene. These mutations prematurely introduce a premature termination codon (PTC: TGA, TAG, and TAA) in the mRNA frame, causing a truncated and non-functional protein that will be eliminated from intracellular surveillance pathways. Nowadays there is no cure for diseases caused by nonsense mutations, but in the last decades, promising results have come from a pharmacological approach, called suppression therapy. This approach uses specific drugs having readthrough activity, known as TRIDs (Translational Readthrough Inducing Drugs), which permit the insertion of a near-cognate-tRNA in correspondence with a PTC during protein translation, allowing the correct development of a functional full-length protein. Our study is focused on investigating three molecules, NV848, NV914 and NV930, patented by Pibiri-Lentini group, that have shown readthrough activity in different nonsense model diseases. Specifically, elucidating their Mechanism of Action in the PURE-LITE system and exploring their readthrough activity in a choroideremia nonsense model system have been the goals of our efforts. PURE-LITE system is a highly purified, eukaryotic cell-free protein synthesis system, that allows the investigation of both the termination of protein synthesis in the P-site catalyzed by the RF complex (eRF1/eRF3/ribosome) and the readthrough via mispairing at the termination codon by a near-cognate tRNA when a PTC enter into the 40S A-site ribosome subunit. Simultaneously, chronic treatment and protein expression analyses was performed on Choroideremia nonsense cell model system to study their readthrough activity. Our results have shown both that the mechanism of action of these molecules is different by their precursor Ataluren, and in addition their readthrough activity with the rescue of Rep1 protein
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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