1,720,984 research outputs found
Investigation of mosaicism sources in Alzheimer’s disease. A focus on nucleotide variants and LINE-1 copy number variants.
Get PDFTechnological advancements, in the form of SNPs arrays and whole genome sequencing provided high-throughput capability in investigating both the quantity and the sequence of cellular DNA. Throughout their extensive applications, several types of variants have been identified to generate mosaicism, the phenomenon characterized by the presence of cells with genetic differences within an organism. In humans, mosaicism has been found to be highly pervasive in both healthy and impaired brains, although its roles and its potential pathological effects are not yet fully understood. Among all the types of somatic variants found to concur in mosaicism, single nucleotide variants and insertions of retrotransposons are of particular interest. Single nucleotide variants (SNVs) are mutations that affect single positions of the genome, and although are predominantly physiological, due to the intrinsic error rate of the DNA replication process [McCulloch and Kunkel, 2008], have been found to cause several brain-related diseases, such as malformations of the brain [Gleeson et al., 2000; Rivière et al., 2012] and severe epileptic brain malformation [Lee et al., 2012; Poduri et al., 2012]. Retrotransposons instead, are a class of repetitive elements which can mobilize within the genome and increase, as a consequence of the process, their copy number. Through this, retrotransposons can shape the human genome by generating structural variants and possibly lead to gene function alterations. Among all the retrotransposons, the LINE-1 family (L1) is the only thought to be still active in humans, and therefore able to concur to mosaicism.
In Alzheimer’s disease (AD), which is the most common neurodegenerative disorder characterized by the accumulation of plaques composed of amyloid β, neurofibrillary tangles containing Tau, synaptic loss and neuronal death, mosaicism has been detected. A recent publication demonstrated that a pathogenic SNVs in PIN1 gene, that result in the loss-of-function mutation of the protein, can lead to tau phosphorylation and aggregation, suggesting therefore a possible link between SNVs and the appearance of tau pathology in AD brains [Park et al., 2019]. Moreover, multiple observation linked AD-key proteins (such as Tau and TDP-43) with the reactivation of retrotransposons [Krug et al., 2017; Saleh et al., 2019]. However, the real impact of SNVs and retrotransposons in AD still remain largely unknown.
Motivated by this lack of knowledge, I decided to investigate SNVs abundance and retrotransposon copy number (CNV), mainly L1’s, using AD post-mortem tissue samples. Giving the current technological limitations that affect mosaicism detection, the dataset was studied by coupling two different strategies and by developing a new targeted sequencing approach. In order to call the highest number of SNVs with the highest quality possible, the densest SNP array available to date (i.e. with the highest number of different SNP probes) was applied upon cerebellum, frontal cortex and kidney samples that belonged to the same individuals. Despite arrays were also used to assess retrotransposon CNV content, they are ineffective in the detection of new retrotransposition events. For this reason, and to further expand SNVs detection to the whole genome, it was applied, as a second strategy, short-reads high coverage (~100x) whole genome sequencing additionally extending the analyses to temporal cortex and hippocampus tissues. Thanks to this approach, it was also unveiled, for the first time to my knowledge, the presence of multi-nucleotide somatic variants in brain (MNVs), a class of variants characterized by two nearby SNVs within the same haplotype.
Finally, although whole genome sequencing strategies were proven to be successful in retrotransposition genotyping, being able to uniquely map short reads originated from repetitive elements to specific genomic regions is currently problematic. Therefore, CNVs, polymorphism and structural variants in overlap with repetitive elements may remain undetected, an aspect that would be even more exacerbated for somatic variants. To improve mapping specificity and resolution, we developed a targeted sequencing approach designed to specifically amplify and sequence both the genomic upstream and the 5’ region of a subset of ~3000 full-length L1. We named this technology LIFE-seq from LINE-1 Five prime End sequencing. I contributed by developed an analysis pipeline able to genotype sequenced loci, testing it upon a subset of the AD dataset
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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