1,721,191 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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
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
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MORC Family ATPases Required for Heterochromatin Condensation and Gene Silencing
Transposons and genes are silenced in eukaryotes through DNA methylation. In this work, mutations in the Arabidopsis genes CRT1 and CRH6, two ATPases in the conserved Microrchidia (MORC) family, are found to release silencing of DNA methylated transposons and genes without an accompanying loss of DNA methylation. The loci upregulated in crt1 and crh6 mutants are located primarily in the regions of pericentromeric heterochromatin. CRT1 and CRH6 are located in small nuclear bodies adjacent to the regions of condensed pericentromeric heterochromatin called chromocenters. In the absence of MORC function, chromocenters decondense and interactions between pericentromeric and euchromatic regions increase. The single Caenorhabditis elegans MORC homolog is also shown to be required for gene silencing. These studies demonstrate that MORC ATPases are required for proper heterochromatin condensation and have a conserved role in gene silencing in eukaryotes
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Mechanisms of DNA methylation control and epigenome engineering
Cytosine DNA methylation is an evolutionarily conserved epigenetic mark that plays critical roles in diverse biological processes, including gene and transposon silencing and imprinting. In mammals, DNA methylation mostly occurs in the symmetric dinucleotide CG sites. In the model plant Arabidopsis thaliana, DNA methylation frequently occurs at cytosine bases in all sequence contexts (CG, CHG and CHH, where H represents A, C or T). In Arabidopsis, de novo DNA methylation is established by a process known as RNA-directed DNA methylation (RdDM). RdDM in plants not only requires the upstream production of 24-nucleotide (nt) small interfering RNAs (siRNAs) and the downstream recruitment of de novo DNA methyltransferase DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), the production of RNA polymerase V (Pol V)-dependent intergenic non-coding (IGN) transcripts plays a crucial role likely in serving as scaffolds for siRNAs binding. Pol V is required for DNA methylation and gene silencing and has been shown to be transcriptionally active in vitro. However, the characteristics of Pol V transcripts is poorly understood probably due to its low abundance. In this dissertation, to better understand the features of Pol V transcripts in vivo, I will first describe the application of a technique modified from global nuclear run-on (GRO) assay to characterize nascent Pol V transcripts at genome-wide level. With this technique, we captured Pol V nascent transcripts and we uncovered a novel mechanism of ARGONAUTE4/6/9 (AGO4/6/9) dependent, small-RNA-guided co-transcriptional slicing of nascent Pol V transcripts. With the fast development of genome editing recent years, epigenetic modification including targeted DNA methylation and demethylation also becomes attractive for its capability of stably regulate gene expression. In order to develop site-specific and efficient tools for DNA methylation targeting, we tethered artificial zinc finger protein recognizing specific DNA sequence to various RdDM proteins (ZF-RdDM) in Arabidopsis. With this tool, we studied the hierarchy of action within RdDM pathway by testing their ability to target methylation in different mutant backgrounds. Also, at thousands of ZF-RdDM off target sites, we characterized the ectopic siRNAs production, Pol V recruitment and DNA methylation establishment and found that simultaneously recruiting both arms of the RdDM pathway, siRNA biogenesis and Pol V recruitment, dramatically enhanced targeted methylation. We then also developed a tool to target DNA demethylation in plants by fusing the catalytic domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and an artificial zinc finger protein or CRISPR/dCas9 system. Finally, I will discuss DNA methylation landscape in human embryonic stem cells (hESCs). hESCs are morphologically and transcriptionally similar to stem cells derived from the mouse post-implantation epiblast. Thus, hESCs are typically considered to exhibit ‘primed’ pluripotency. Various culture conditions have been developed to promote maintenance and self-renewal of hypomethylated ‘naive’ hESCs. We have discovered that reverting primed hESCs to naive hESCs results in a Stage Specific Embryonic Antigen 4 (SSEA4)-negative population with a transcriptional program resembling the human pre-implantation epiblast. However, we also discovered that the methylation landscape of naive hESCs in vitro is distinct from human epiblast in vivo with a lost ‘memory’ of methylation state at primary imprints and human oocyte
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Epigenetic regulation of gene silencing and DNA replication in Arabidopsis thaliana
Chemical modifications to histones and DNA regulate various biological processes including transcriptional silencing and DNA replication. One of the most well studied chromatin modifications in Arabidopsis thaliana is DNA methylation and its role in silencing transposable elements (TEs) and genes. In Arabidopsis, certain DNA methylation pathways are controlled by histone H3 lysine 9 methylation, a histone modification associated with heterochromatin. A much less characterized heterochromatic mark is histone H3 lysine 27 monomethylation (H3K27me1). Two SET domain proteins, ARABIDOPSIS TRITHORAX-RELATED PROTEIN5 (ATXR5) and ATXR6, were found to catalyze H3K27me1. In atxr5 atxr6 double mutants, transcriptional reactivation of TEs was observed without global defects in DNA methylation levels. Thus, unlike H3K9 methylation, H3K27me1 appeared to be involved in a silencing system independent of DNA methylation. In addition to transcriptional reactivation of TEs, we found that atxr5 atxr6 mutants show increased copies of heterochromatic DNA, suggesting that ATXR5 and ATXR6 are involved in a pathway that prevents heterochromatin from over-replicating. To gain better understanding about DNA methylation and H3K27me1, we performed genome-wide mapping of these chromatin marks. We profiled DNA methylation in a comprehensive list of mutants and characterized locations different DNA methylation pathways act in the genome. We also profiled H3K27me1 and found that it is enriched at sites heavily DNA methylated. Sites of over-replication in atxr5 atxr6 mutants correlated with sites normally enriched with H3K27me1, consistent with the fact that ATXR5 and ATXR6 catalyze this mark.Given the overlap between H3K27me1 and DNA methylation across the genome, we explored the relationships between ATXR5 ATXR6 and DNA methylation in regulating gene silencing and DNA replication. We found that ATXR5 ATXR6 and DNA methylation cooperatively silence TEs through independent pathways, indicating that multiple pathways redundantly silence many TEs across the Arabidopsis genome. In contrast, we found that ATXR5 ATXR6 and DNA methylation antagonistically regulate heterochromatic DNA replication, suggesting a complex relationship between these chromatin marks in regulating transcriptional silencing TEs and heterochromatic DNA replication.Taken together, our results provide insight into the roles of epigenetic marks in regulating gene silencing and DNA replication
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The Genetics of de novo Methylation in Arabidopsis thaliana
Cytosine DNA methylation is an ancient form of transcriptional control that is conserved across all kingdoms of eukaryotes. DNA methylation plays a major role in silencing of selfish genetic elements, such as transposons. Additionally, in some instances, DNA methylation is required for genomic imprinting and regulation of endogenous genes. In the model plant Arabidopsis thaliana, at least three pathways, each with its own methyltransferase, maintain DNA methylation. MET1 targets CG dinucleotide sequences; due to the inherent symmetry across DNA strands, MET1 is able to recognize hemimethylated sites after DNA replication, thus maintains faithful methylation patterns. CMT3 typically has preference for CHG sites (where H is A, T, or C), and is targeted to chromatin via its chromodomain, which has specificity for histone 3 lysine 9 dimethylation--another epigenetic mark associated with heterochromatin. Finally, DRM2 maintains CHH, or asymmetric, methylation through targeting by a dual siRNA/long non- coding RNA pathway termed RNA-directed DNA methylation (RdDM). It should be noted that CMT3 and DRM2 are both capable of methylating non-CG sites. While all three methyltransferases maintain existing DNA methylation patterns, only the RdDM pathwayestablishes the mark in all sequence contexts, in a process known as de novo methylation. In this dissertation I will describe both forward and reverse genetic techniques I have used to uncover factors required for de novo methylation. For both techniques, I made use of the FWA transgene. In wild-type plants, the RdDM pathway is able to target, methylate, and silence the transgene at the repeats in its 5' UTR. However, in RdDM mutants, the transgene remains unmethylated and expresses, leading to a late-flowering phenotype. From a mutagenesis screen, I discovered novel mutations in 11 genes required for DNA methylation establishment. I will describe the methodologies of cloning and characterizing those mutants. Additionally, from the same study, I was able to show a de novo methylation phenotype from previously described RdDM mutant alleles.In a reverse genetic screen, utilizing a collection of insertional mutations in known or putative RNA binding proteins, I helped characterize a known RNA splicing factor, the first such RNA processing protein shown to be required for RdDM. I also showed that two partially redundant paralogs of the IDN2 RNA-binding protein are required for RdDM and de novo methylation. Further biochemical analysis revealed that the paralogs form a complex with IDN2. In collaboration with a structural biology group, we solved the structure of the RNA binding motif of IDN2.Finally, I will discuss the data explicating the relationship between histone 3 lysine 4 (H3K4) demethylases and the RdDM pathway. We made the surprising discovery that active demethylation is required for RdDM maintenance, but not establishment. In sum, the work in this dissertation contributes to our knowledge of the components and mechanism of RdDM, and how the RNA polymerase-dependent pathway is affected by perturbations in local chromatin
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