1,720,959 research outputs found

    Participação das vias da fosfoinositídeo-3-quinase (PI3K) e da proteína quinase C (PKC) na regulação da expressão do receptor B1 para as cininas na veia porta de rato

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    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pos-Graduação em Farmacologia

    Characterization of the protein interaction profile of the human kinase Nek4 and assignment of its functional context

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    Orientador: Jörg KobargTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: As Neks são proteínas quinases similares a NIMA, proteína que é indispensável para a entrada em mitose de células de Aspergillus nidulans. Em humanos foram identificadas 11 Neks (1-11) e, estudos crescentes vêm demonstrando a participação destas em diversas funções celulares além do controle do ciclo e divisão celular. A Nek4 é um dos maiores membros dessa família e sua relação com a manutenção ciliar e resposta ao DNA danificado já foi demonstrada. Contudo, seus parceiros de interação e substratos são ainda desconhecidos. Para melhor compreender o papel da Nek4 foi realizado um estudo de interatoma para identificar novos processos biológicos com os quais a Nek4 está envolvida. Inicialmente foi identificada uma nova isoforma para a Nek4 e assim, realizou-se o estudo de interatoma para as duas isoformas com a finalidade de comparar o perfil de interação das duas proteínas. As duas isoformas da Nek4 foram expressas em células humanas e após imunoprecipitação seguida de identificação por espectrometria de massas, foram identificadas 474 proteínas que interagem com a isoforma 1 da Nek4, Nek4.1 e 149 para a isoforma 2, Nek4.2. Dentre as proteínas identificadas, 102 interagem com ambas isoformas da Nek4. Nossos resultados confirmam o envolvimento da Nek4 com a resposta ao DNA danificado, função ciliar, estabilização dos microtúbulos e ainda sugerem o envolvimento da Nek4 em funções completamente novas, como processamento de RNAm, resposta ao estresse, controle de qualidade das proteínas e apoptose. Entre os parceiros de interação encontramos importantes proteínas como TRAP-1, Whirlin, PCNA, 14-3-3?, Btf, PARP-1, SRSF1, PAI-RBP1 e KAP-1. As duas isoformas compartilham funções que não foram ainda descritas para os membros da família Nek e a isoforma 1 ainda apresenta funções que já foram descritas para outros membros da família. Aliado ao resultado da imunoprecipitação ainda foram realizadas imunofluorescências que permitiram verificar a localização da Nek4 em diferentes estruturas celulares, como os speckles nucleares e a mitocôndria, corroborando com a função no processamento de RNAm e apoptose. O experimento de imunoprecipitação seguido de identificação por espectrometria de massas também apontou para a possibilidade de autofosforilação e dimerização da Nek4. Além disso, foi possível observar diferenças entre o perfil de interação das duas isoformas da Nek4, sendo que a isoforma 1 interage com proteínas que mantém funções biológicas similares a outras Neks, que a isoforma 2 não apresentaAbstract: Neks are serine-threonine kinases that are similar to NIMA, a protein found in Aspergillus nidulans which is essential for cell division. In humans there are eleven Neks (1-11) which are involved in different biological functions besides the cell cycle control. Nek4 is one of largest members of the Neks family and has been related to the primary cilia formation and in DNA damage response. However, its substrates and interaction partners are still unknown. Thus in an attempt to better understand the role of Nek4 we performed an interactomics study to find new biological processes in which Nek4 is involved. Besides, we described here a novel Nek4 isoform and compared the interactomics profile of these two Nek4 proteins. Isoform 1 and isoform 2 of Nek4 were expressed in human cells and after an immunoprecipitation followed by mass spectrometry, 474 interacting proteins were identified for isoform 1 and 149 for isoform 2 of Nek4. 102 proteins are common interactors between both isoforms. Our results confirm Nek4 involvement in the DNA damage response, cilia maintenance and microtubules stabilization, and raise the possibility of new functional contexts including mRNA processing, apoptosis signaling, stress response, translation and protein quality control. Among the interaction partners, we found important proteins such as TRAP-1, Whirlin, PCNA, 14-3-3?, Btf, PARP-1, SRSF1, PAI-RBP1 and KAP-1. We could observe that both isoforms share functions that are new to the Nek family, and isoform 1 apparently has also maintained functions which have already been established to other Nek family members. From our immunoprecipitation followed by mass spectrometry experiment a possible site for Nek4 autophosphorylation and dimerization was identified. This study provides new insights into Nek4 functions, identifying new interaction partners, localization to new cellular compartment and further suggests an interesting difference between isoform 1 and the novel isoform 2 of Nek4. Nek4 isoform 1 may have maintained similar roles compared to other Neks and these roles are not related to isoform 2DoutoradoBioquimicaDoutora em Biologia Funcional e Molecula

    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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