1,720,957 research outputs found
Mind the gap: exploring the genetic regulation behind optic fissure closure in chicken
Optic fissure closure (OFC) is an evolutionarily conserved process during ocular development, in which opposing edges of the epithelial tissue in the ventral eye will fuse to close the optic fissure and form the complete circumferential retina. Failure of OFC results in ocular coloboma, a sight disorder which manifests as a keyhole-like gap at any point along the ventral eye. Notably, ocular coloboma exhibits genetic heterogeneity, with over 40 causative disease genes so far identified, and over 100 genomic loci associated with the condition. However, genetic causes for more than 80% of coloboma cases remain unknown, despite the application of whole exome and whole genome sequencing, suggesting non-coding cis-regulatory loci may harbour the causative genetic defect in some of these cases. In this project, I used chicken OFC as a model to explore stage-specific gene expression and to discover novel genomic loci regulating OFC.
By conducting bulk RNA-sequencing (RNA-seq) on fusing optic fissure tissue during OFC, a total of 106 genes were identified as fusion specific enriched genes using this approach, including previously known ocular coloboma associated genes (NTN1 and PAX2). To identify differentially accessible chromatin region specific to OFC, bulk Assay for Transposase-Accessible Chromatin (ATAC-seq) was conducted. 3869 open chromatin regions, known as peaks, with fusion specific enriched accessibility were identified genome-wide. Upon the integration of RNA-seq and ATAC-seq datasets, I discovered 105 fusion specific enriched peaks that were located in proximity to fusion specific enriched genes, providing candidate loci for the cis-regulation of OFC.
A NTN1 fluorescent OFC reporter chicken line (NTN1-T2A-GFP) was used to fluorescently label cells that directly mediate fusion, defined as the pioneer cells region. By comparing the transcriptome of NTN1-GFP positive pioneer cells to the neighbouring GFP negative cells, 433 genes were shown to be significantly enriched in the pioneer region. 5 genes with significantly enriched expression in the GFP-positive cells (GALNT6, CLYBL, DVL1, ZIC1, EGF) were validated in vivo by in-situ hybridisation with enriched expressions at the pioneer region. Functional annotation and protein network analysis of these cells showed overrepresentation of the pathway terms including MET/HGF and Akt-PI3K signaling. By incorporating the both the NTN-GFP positive cells transcriptome and in-situ hybridisation data with the lab-generated single-nuclei RNA-seq (snRNAseq) data, 2 clusters of cells in the pioneer region with different transcriptomic profiles were identified.
By conducting ATAC-footprinting analysis, TEAD1/3 was shown as the most differentially bound transcription factor (TF) during OFC. This echoes with previously published data, in which loss of function mutations on TEAD co-activator YAP1 resulted in ocular coloboma in humans and zebrafish. By further incorporating the existing RNA- seq data on the pioneer region into the ATAC-seq footprinting analysis, 42 peaks were predicted to harbour at least one binding site for pioneer cell enriched TFs and were situated next to a pioneer cell enriched gene, which were therefore considered as strong enhancers candidates regulating OFC.
In summary, this study provides insights to understand the gene regulation in OFC by generating the first published ATAC-seq dataset for the fusing optic fissure and revealed plausible candidates for ocular coloboma-causing loci. Secondly, expression of novel OFC-related genes and pathways were identified by a combination of bulk RNA-seq and sn-RNAseq, enhancing our understanding towards the overall OFC mechanism
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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