1,720,962 research outputs found
Role of the stemness transcription factor ZNF521 in MLL-rearranged acute myeloid leukemia
Full text linkAcute myeloid leukemias (AMLs) that harbor translocations involving the MLL gene on chromosome 11q23 generate fusion transcripts that give rise novel fusion proteins with potent oncogenic properties and capable to destabilize the normal transcriptional activities. MLL fusion oncoproteins have been shown to initiate leukemic transformation primarily by overexpression of a specific set of genes, including HOXA4, 5, 6, 7, 9, 10 (overall defined as “HOXA-code” genes), MEIS1 (a cofactor of “HOXA-code” proteins) and MYB. It‘s well established that the majority of these genes are involved in normal programs of self-renewal, maintenance and proliferation of hematopoietic stem cells and early progenitors. Therefore is not surprise that the deregulation of the stemness genetic programs due to MLL fusion oncogenes is a crucial step for leukemic transformation. To identify new stemness genes involved in MLL-mediated transformation we performed gene set enrichments analysis (GSEA) using public database of geneset profiles of normal hematopoietic cells in a cohort of pediatric AML previously analyzed. These analyses identified a series of genes more highly expressed in MLL-rearranged AML including the well known HOXA9, HOXA5 and MEIS1, together with an apparently novel gene: ZNF521 or zinc finger protein 521
ZNF521 encodes for a zinc finger protein and, like HOXA9, is strongly expressed by CD34+ hematopoietic stem cells and drastically decreases during differentiation. To evaluate the importance of ZNF521 in MLL-rearranged AML, we performed a series of functional and mechanistic studies to uncover the role of ZNF521 in MLL-rearranged cells. We used lentiviral vectors to silencing the ZNF521 and expression vectors to induce MLL-fusion proteins such as MLL-AF9. These studies, both in vitro and ex vivo, demonstrate that the growth inhibition, reduced clonogenicity and cell cycle arrest induced by ZNF521 depletion is mediated through enhanced myeloid differentiation. Moreover, we demonstrate that ZNF521 is a direct target of MLL-fusion oncoproteins such as MLL-AF9 and MLL-ENL.
Collectively, these findings identify ZNF521 as critical effector of MLL fusion in leukemogenesis that might be targeted to overcome the differentiation block associated with MLL-rearranged AML and thus highlight ZNF521 as potential therapeutic target in treating this subtype of aggressive leukemia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Zebrafish Ortholog of Human DOT1L Regulates Primitive and Transient Definitive Hematopoiesis and Controls hoxa9 and meis1 Expression
No full textDispelling the Myths Behind First-author Citation Counts
Full text linkWe 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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