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    UPREGULATION OF PARAOXONASE-2 IN CLEAR CELL RENAL CELL CARCINOMA: POTENTIAL FOR ANTICANCER THERAPY

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    Il carcinoma renale a cellule chiare (ccRCC) è il sottotipo più comune tra le neoplasie renali ed è caratterizzato sia da una scarsa sensibilità alla chemioterapia e radioterapia che da una grande capacità di metastatizzare. Nonostante i recenti progressi nell’identificazione di nuove molecole bersaglio, la prognosi dei pazienti con ccRCC rimane negativa ed un terzo dei pazienti con carcinoma a cellule renali presenta malattia metastatica al momento della diagnosi. Pertanto, è necessario scoprire nuove molecole per la diagnosi precoce, per una prognosi più accurata o per la sviluppo di una terapia mirata. In questo studio, abbiamo focalizzato la nostra attenzione sull'enzima Paraoxonasi-2 (PON2), che appartiene alla famiglia delle paraoxonasi umane (PON). PON2 è un enzima intracellulare legato alla membrana, espresso in modo ubiquitario nei tessuti umani, la cui upregolazione è stata descritta in diversi tipi di tumori solidi, suggerendo il suo possibile coinvolgimento nella progressione del cancro e nella chemio-radioresistenza. Per approfondire il coinvolgimento dell’enzima PON2 nel metabolismo delle cellule tumorali, le linee cellulari ccRCC umane sono state trasfettate con vettori plasmidici codificanti short hairpin RNA (shRNA) che hanno come target l’mRNA di PON2. Successivamente sono stati valutati gli effetti del silenziamento del gene PON2 sulla vitalità cellulare, sulla migrazione e sulla sensibilità al trattamento chemioterapico. I nostri risultati hanno dimostrato che PON2 potrebbe rappresentare un interessante bersaglio terapeutico per il ccRCC, poiché la downregolazione dell’enzima ha comportato una diminuzione della capacità proliferativa e di migrazione cellulare, e una maggiore sensibilità delle cellule alla chemioterapia.Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal malignancies which is characterized by lack of sensitivity to chemo- and radiotherapy and a marked ability to metastasize. Despite recent advances in identifying novel molecular targets, the prognosis of ccRCC patients remains poor, and one-third of ccRCC patients show metastatic disease at diagnosis. Hence, identifying novel molecules for diagnosis, more accurate prognosis or for targeted therapy is mandatory. In this study, we focused on the enzyme Paraoxonase-2 (PON2) which belongs to human paraoxonase (PON) family. PON2 is an intracellular membrane-bound enzyme ubiquitously expressed in human tissues whose upregulation was described in a variety of solid tumors suggesting its possible role in cancer progression and chemo-radio-resistance. To explore the role of PON2 in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short hairpin RNAs targeting PON2 transcript. The effects of PON2 gene silencing on cell viability, migration, and sensitivity to chemotherapeutic treatment were subsequently assessed. Our results demonstrated that PON2 may represent an interesting therapeutic target for ccRCC since enzyme downregulation resulted in a decreased cell proliferation and migration ability, and enhanced cell sensitivity to chemotherapy

    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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    Paraoxonase-2 shRNA-mediated gene silencing suppresses proliferation and migration, while promotes chemosensitivity in clear cell renal cell carcinoma cell lines

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    Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal tumor. Despite recent advances in identifying novel target molecules, the prognosis of patients with ccRCC continues to be poor, mainly due to the lack of sensitivity to chemo- and radiotherapy and because of one-third of renal cell carcinoma patients displays metastatic disease at diagnosis. Thus, identifying new molecules for early detection and for developing effective targeted therapies is mandatory. In this work, we focused on paraoxonase-2 (PON2), an intracellular membrane-bound enzyme ubiquitously expressed in human tissues, whose upregulation has been reported in a variety of malignancies, thus suggesting its possible role in cancer cell survival and proliferation. To investigate PON2 involvement in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short harpin RNAs targeting PON2 transcript and the impact of PON2 silencing on cell viability, migration, and response to chemotherapeutic treatment was then explored. Our results showed that PON2 downregulation was able to trigger a decrease in proliferation and migration of ccRCC cells, as well as an enhancement of cell sensitivity to chemotherapy. Thus, taken together, data reported in this study suggest that the enzyme may represent an interesting therapeutic target for ccRCC

    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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