1,721,020 research outputs found
Epigenetic modulations rendering cell-to-cell variability and phenotypic metastability
Full text linkTumor cells display phenotypic plasticity and heterogeneity due to genetic and epigenetic variations which limit the predictability of therapeutic interventions. Chromatin modifications can arise stochastically but can also be a consequence of environmental influences such as the microenvironment of cancer cells. A better understanding of the impact and dynamics of epigenetic modulation at defined chromosomal sites is required to get access to the underlying mechanisms. We investigated the epigenetic modulations leading to cell-to-cell heterogeneity in a tumor cell line model. To this end, we analyzed expression variance in 80 genetically uniform cell populations having a single-copy reporter randomly integrated in the genome. Single-cell analysis showed high intraclonal heterogeneity. Epigenetic characterization revealed that expression heterogeneity was accompanied by differential histone marks whereas contribution of DNA methylation could be excluded. Strikingly, some clones revealed a highly dynamic, stochastically altered chromatin state of the transgene cassette which was accompanied with a metastable expression pattern. In contrast, other clones represented a robust chromatin state of the transgene cassette with a stable expression pattern. Together, these results elucidate locus-specific epigenetic modulation in gene expression that contributes to phenotypic heterogeneity of cells and might account for cellular plasticity.Fil: Spencer, Shawal. Helmholtz Centre For Infection Research; AlemaniaFil: Gugliotta, Agustina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Gödecke, Natascha. Helmholtz Centre For Infection Research; AlemaniaFil: Hauser, Hansjörg. Helmholtz Centre For Infection Research; AlemaniaFil: Wirth, Dagmar. Helmholtz Centre For Infection Research; Alemania. Hannover Medical School; Alemani
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
Dispelling 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
Stability of single copy transgene expression in CHOK1 cells is affected by histone modifications but not by DNA methylation
No full texttIntraclonal heterogeneity of genetically modified mammalian cells has been observed as a phenomenonthat has a strong impact on overall transgene expression levels and that limits the predictability of trans-gene expression in genetically modified cells, thereby hampering single cell based screening approaches.The underlying mechanism(s) leading to this variance are poorly understood. To study the dynam-ics and mechanisms of heterogeneity of early stage silencing we analyzed the expression in morethan 100 independent clones of CHOK1 cells that harbour genetically stable integrates of single copyreporter cassettes driven by EF1alpha and CMV promoters. Single cell analysis showed intraclonal vari-ability with heterogeneity in expression in genetically uniform populations. DNA methylation is a wellknown mechanism responsible for silencing of gene expression. Interestingly, loss of expression wasnot associated with DNA methylation of the CMV promoter. However, in most of the clonal popula-tions expression could be increased by inhibitors of the histone deacetylases (HDACi) suggesting thatheterogeneity of transgene expression is crucially governed by histone modifications. Further, to deter-mine if the epigenetic status of transgene expression is governed by the chromosomal integration locuswe targeted heterologous expression cassettes into two chromosomal sites using recombinase medi-ated cassette exchange (RMCE). The expression status of a particular clone was faithfully re-establishedwhen the same promoter used. In this way the problem of early stage cell clone instability can bebypassed. However, upon introduction of an unrelated promoter methylation-independent silencingwas observed. Together, these results suggest that histone modifications are the relevant mechanisms bywhich epigenetic modulation of transgene expression cassettes is governed in the early phase of clonegeneration.Fil: Spencer, Shawal. Helmholtz Centre for Infection Research; AlemaniaFil: Gugliotta, Agustina. Helmholtz Centre for Infection Research; Alemania. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Koenitzer, Jennifer. Boehringer Ingelheim Pharma; AlemaniaFil: Hauser, Hansjörg. Helmholtz Centre for Infection Research; AlemaniaFil: Wirth, Dagmar. Helmholtz Centre for Infection Research; Alemania. Hannover Medical School. Department of Experimental Hematology; Alemani
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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