1,720,973 research outputs found

    Transient naive reprogramming corrects hiPS cells functionally and epigenetically

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    Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function1,2,3,4,5,6,7,8. These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory

    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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    An integrative analysis of the human placental transcriptome

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    Pregnancy outcome is inextricably linked to placental development, which is strictly regulated both temporally and spatially by mechanisms that are only partially understood. Although the placenta is absolutely indispensable for fetal development in utero, it remains the least understood human tissue. Although the placenta is a shared organ between the mother and fetus, it is of embryonic origin, and therefore its development is largely regulated by the fetal genome. This overall goal of this research was to investigate three key aspects of human placental gene regulation: (1) The effect of genomic imprinting on gene regulation, (2) the differences in placental gene expression between the sexes, and (3) the co-expression relationships that exist between genes on a transcriptome scale. Firstly, this research identified a window of epigenetic imprinting plasticity for the long non-coding RNA H19, which is heavily implicated in placental development and function. These results suggested that variation in H19 imprinting may contribute to early programming of placental phenotype and highlighted the need for quantitative and robust methodologies to further elucidate the role of imprinted genes in normal and pathological placental development. Secondly, by conducting a transcriptome-scale meta-analysis of sex-biased gene expression, this research revealed that 140 genes are differentially expressed between male and female placentae. A majority of these genes are autosomal, many of which are involved in high-level regulatory processes such as gene transcription, cell growth and proliferation and hormonal function. Of particular interest, all genes in the LHB-CGB cluster were expressed more highly in female placentas, which includes genes involved in placental development, the maintenance of pregnancy and maternal immune tolerance of the conceptus. These results demonstrated that sex-biased gene expression in the normal human placenta occurs across the genome and includes genes that are central to growth, development and the maintenance of pregnancy. Thirdly, by undertaking a comprehensive analysis of human placental gene co-expression using RNA sequencing and the integration of five human and one mouse transcriptome dataset, this research identified clusters of correlated genes, whose patterns of co-expression are highly preserved across human gestation and between human and mouse, subsequently revealing highly conserved molecular networks involved in placental development. Furthermore, by reducing the complexity of the placental transcriptome by summarizing co-expressed genes, this work identified a group of co-expressed genes implicated in preeclampsia and also outlines a novel method for identifying for non-invasive biomarkers of placental development. In summary, each aspect of this PhD research has provided new insights into how gene expression is regulated in the human placenta and has revealed previously unappreciated aspects of the placental transcriptional landscape.Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2015

    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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