1,720,956 research outputs found

    Chromosome Instability, friend or foe: genetic and epigenetic causes in cancer

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    Chromosome Instability (CI) compromises the fidelity of the transmission of the genetic material, and thus, is a grave risk for health. Many genetic diseases including cancer are characterised by CI. However, the leading causes identified so far can be different in each condition. Understanding the specific underlying mechanisms and how cells learn to deal with CI is of great relevance to design ad hoc and personalised therapeutic strategies. With this aim, we have been focused on three research lines: 1) investigating the involvement of DNA methylation in centromere stability and function, 2) unveiling a new player in chromosomal common fragile sites (CFSs) stability, 3) exploiting CI to induce senescence and allow cancer cells’ clearance. By using molecular and cell biology approaches, as well as microscopy techniques, we observed that global DNA methylation loss, a frequent event in cancer cells, undermines the correct loading of centromere proteins resulting in mitotic defects and CI. We also identified a key element, an helicase protein involved in the resolution of RNA:DNA hybrids at CFSs during mitosis, that appears to be critical for cancer cells’ survival. Moreover, we showed that curcumin treatment leads to senescence only tumor cells by increasing their endogenous CI. We also demonstrated that the combination of curcumin treatment and senolytic molecules is able to deplete cancer cells [1]. Our results pave the way for new therapeutic strategies against cancer progression that take advantage of the CI distinctive for each tumor context. We also set the course for DNA methylation essential to maintain centromere functionality and thus chromosomal stability

    RNA Editing Approaches for the correction of nonsense mutation in a cell model for Cystic Fibrosis

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    Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene. In particular, CFTR nonsense (STOP) mutations generate a premature termination codon (PTC) in the mRNA, leading to the production of a shortened and non-functional protein1. Currently, there is no pharmacological therapy that specifically targets nonsense mutations in CF. In this regard, we are exploring the possibility to correct the PTC using different RNA-based editing tools. These systems exploit the Adenosine Deaminases Acting on RNA (ADAR) to convert the adenosine within the PTC into inosine and allow the full-length protein synthesis2. Among these, a compact REPAIRv2 system uses a modified and truncated dCAS13x.1 fused with ADAR2DD that is recruited to the adenosine of PTC by means of a specifically designed guide RNA1. A different system named RESTORE uses specific antisense RNA oligonucleotides (ASOs), complementary to the CFTR mRNA region with the PTC, except for a cytidine-adenosine mismatch that promotes ADAR recruitment3. In addition, we also evaluated phenotypical anomalies of CFTR mutated cells showing morphological differences in comparison to wild type cells4. Our results pave the way to new therapeutical strategies potentially able to correct the nonsense mutations in cystic fibrosis

    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

    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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