1,720,965 research outputs found
Analysis of the induction of the cytoprotective Nrf2 signalling pathway in reticuloendothelial cells from iron-treated mice and HFE Haemochromatosis patients
Get PDFDissecting the role of CENP-E in the maintenance of chromosome alignment
Get PDFO objetivo da mitose é garantir a correta segregação dos cromossomas de modo a originar duas células geneticamente iguais. Quando as células entram em mitose, os seus cromossomas condensam e estabelecem ligações com o fuso mitótico através dos seus cinetocóros de modo a serem dirigidos para o equador da célula. Este processo de alinhamento é um pré-requisito para a correta segregação dos cromossomas, pois erros neste processo resultam em aneuploidia e Instabilidade Cromossómica (CIN). Uma das moléculas chave neste processo de alinhamento é a CENP-E, uma proteína motora pertencente à família das Cinesinas e que se acumula nos cinetocóros durante a mitose. Apesar de estar estabelecida a função desta proteína no processo de alinhamento dos cromossomas, a sua importância para manutenção desse alinhamento é desconhecida. Com a objetivo de a elucidar, foi determinada a dose óptima de inibição de CENP-E em linhas celulares humanas com e sem CIN, usando para tal três inibidores independentes: PF-2771, GSK923295A e Compound A, que atuam através de mecanismos alostéricos distintos. Usando um rastreio de alto rendimento, foram calculadas as doses óptimas de inibição total e parcial de CENP-E e posteriormente verificada a sua ação na manutenção do alinhamento dos cromossomas através de microscopia em células vivas de alta resolução. Neste trabalho mostramos que a CENP-E é essencial para a manutenção do alinhamento dos cromossomas em células humanas com e sem CIN. A sensibilidade relativa dos inibidores é proporcional para o PF-2771 e para o GSK923295A quando comparamos linhas celulares com e sem CIN. Contudo, células diplóides são menos sensíveis à inibição da CENP-E quando usado o Compound A, sugerindo que este composto poderá ter um valor terapêutico superior no tratamento do cancro. Estes resultados permitem aprofundar o nosso conhecimento acerca do valor terapêutico dos inibidores da CENP-E que são atualmente testados em ensaios clínicos.The goal of mitosis is to ensure faithful segregation of genomic content into two identical daughter cells. As cells enter mitosis, the DNA becomes condensed into mitotic chromosomes, which must establish stable attachments to the mitotic spindle. Upon establishing proper kinetochore-microtubule attachments, chromosomes can then be guided to the center of the cell. Notably, this process of chromosome congression is a prerequisite for faithful chromosome segregation, since errors in this process lead to aneuploidy and chromosomal instability (CIN). One of the key players involved in chromosome congression is CENP-E, a kinesin-like motor protein that is enriched at kinetochores during mitosis. Despite mounting evidence demonstrating a role for CENP-E in chromosome congression, the importance of CENP-E activity once chromosomes are already aligned, is currently unknown. To this purpose, we first determined the optimal dose for inhibiting CENP-E function in both CIN and non-CIN human cell lines using three independent CENP-E inhibitors: PF-2771, GSK923295A and Compound A, which act through distinct allosteric mechanisms. Using high-throughput screening, we calculated the optimal doses required for partial and total CENP-E inhibition and then performed high-resolution live cell imaging to directly test CENP-E function in the maintenance of chromosome alignment. We show that CENP-E is essential for the maintenance of chromosome alignment in both CIN and non-CIN human cells. We find that relative sensitivity to CENP-E inhibitors is proportional for PF-2771 and GSK923295A when comparing CIN and non-CIN cell lines. However, diploid cells are less sensitive to CENP-E inhibition using Compound A, suggesting that this compound may be of higher therapeutic value for the treatment of cancer. Taken together, these results offer insight for our understanding of the therapeutic value of CENP-E inhibitors currently tested in clinical trials
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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