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    A novel nuclear function for the centrosomal serine/threonine kinase Nek2

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    Numerose chinasi che regolano il ciclo centrosomale sono frequentemente regolate in maniera aberrante nelle cellule neoplastiche. Cambiamenti nella loro espressione possono portare ad alterazioni nella duplicazione del centrosoma quindi aneuploide. I tumori delle cellule germinali testicolari sono caratterizzati da amplificazione dei centrosomi la cui causa è ancora largamente sconosciuta. Abbiamo individuato una nuova chinasi centrosomale, Nek2, che risulta up-regolata nei seminomi testicolari in maniera specifica e ne abbiamo caratterizzato la sua funzione nelle cellule germinali neoplastiche. Una scoperta inaspettata del nostro studio è stata la presenza di Nek2 nel nucleo delle cellule germinali di seminoma testicolare, localizzazione ritrovata anche nelle cellule di linea derivanti dai seminomi: le Tcam-2. Inoltre tale localizzazione è stata ritrovata nelle cellule germinali da cui i seminomi derivano: le cellule germinali primordiali e gli spermatogoni più indifferenziati. Tali risultati suggeriscono un ruolo di Nek2 come marcatore di staminalità delle cellule germinali maschili, mantenuto anche nella trasformazione neoplastica. Abbiamo inoltre dimostrato che la localizzazione nucleare di Nek2 non è una caratteristica peculiare dei seminomi testicolari ma è principalmente localizzata nel nucleo in diversi tipi di tumore. Nelle cellule tumorali inoltre Nek2 è presente in splicing speckles dove associa con numerosi fattori di splicing come la proteina SR (ASF/SF2), hnRNP (A1, F and H), e la proteina STAR Sam68. Il nostro studio dimostra che Nek2 è in grado di fosforilare Sam68 e di modularne l’attività di splicing. Questi risultati identificano un nuovo ruolo nucleare per Nek2Protein kinases that regulate the centrosome cycle are often aberrantly regulated in neoplastic cells. Changes in their expression or activity can lead to perturbations in centrosome duplication and aneuploidy. In addition, many centrosomal protein kinases participate to other aspects of cell cycle progression. Testicular germ cell tumors (TGCTs) are characterized by amplification of centrosomes through unknown mechanisms. We have discovered that the centrosomal kinase Nek2 is overexpressed in testicular seminomas and we have characterized its function in neoplastic germ cells. One unexpected finding of our study was the nuclear localization of Nek2 in germ cells of patients. The same nuclear localization was observed in the seminoma cell line Tcam-2. We found that Nek2 was localized in the nucleus also in undifferentiated embryonal male primordial germ cells (PGCs) and in spermatogonial stem cells from post-natal testis. These results suggest that nuclear Nek2 is a novel marker of the undifferentiated stage of male germ cells that is maintained in testicular seminomas, but not in other TGCTs. The nuclear localization of Nek2 is not a unique feature of testicular seminomas, we show that Nek2 is mainly distributed in the nucleus of cancer cells from other tissues, including breast, prostate and colon cancer cells. The subnuclear distribution of Nek2 in speckles closely resembled that of many regulators of pre-mRNA splicing. We found that Nek2 physically associates with several splicing factors, such as SR proteins (ASF/SF2), hnRNPs (A1, F and H), and the STAR protein Sam68. We focused our study on Sam68 because this splicing regulator is also up-regulated in breast and prostate carcinomas like Nek2. Our study shows that Sam68 is also overexpressed in testicular seminomas but not in other TGCTs, like Nek2. Moreover, Nek2 phosphorylates Sam68 and affects Sam68-dependent splicing of CD44v5 pre-mRNA, an alternatively spliced form of the receptor, frequently altered in cancer cells, that promotes cell proliferation and invasiveness. These results identify a novel nuclear function of Nek2 and suggest that modulation of alternative splicing events by this kinase can contribute to neoplastic transformatio

    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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