1,720,956 research outputs found
DNA, variations on the theme
Get PDFMolecular biology's central dogma, laid down in 1950s, affirmed that genetic information flows from DNA to RNA to protein synthesis. For a long time, the first element of this logic scheme, DNA, was regarded as inactive molecule with the sole purpose to act as a repository of genetic code. Indeed, the molecular dialogue between DNA and proteins has been generally interpreted as an univocal relationship between an inert partner (nucleic acid) and a versatile one (proteins), that remodels DNA as a clay object. Rather, has been emerged that each kind of interactions between macromolecules requires a mutual structural adaptation and chemical complementarity.
As in Kurosawa’s classic movie “Rashomon” (1950) the same central event, a heinous crime, is recalled from the differing perspective of each character (a bandit, a samurai, samurai’s wife and a woodcutter) this present study aims to highlight some different, but complementary, aspects of the full dynamic repertoire of DNA macromolecules. In the first part of this thesis, I will demonstrate that DNA, according to a peculiar three dimensional arrangement, is not only a simple recipe for proteins production but something more. In particular, I will focus on guanosine quadruplex structure, a not canonical B-form of DNA could be described through multiple points of view.
On one side, synthetic guanosine quadruplex can act as “smart” biomolecules able to recognize multiple targets, with potential implications both as diagnostic as well as therapeutic agent. This short DNA/RNA sequences, called aptamers, according to a unique molecular flexibility, are able to recognize and bind a broad range of targets with specificities reminiscent those exhibited by antibodies. As working model, here I will present a detailed characterization in vitro of not physiological guanosine rich sequences able to bind human thrombin, a protein of physiological and pathological relevance. Our research was aimed to describe the relative role of the structural modules composing their molecular architecture. This allowed us to propose a structure activity relationship of synthetic G quadruplex aptamers, in order to fully rationalize and optimize their binding property.
On the other side, G-quadruplex forming sequences are also found in human genome. Some of them have been described as unique biochemical on/off switch able to regulate tumorigenic pathways.
In particular, the expression of the oncogene c-Myc is controlled through the formation of non–B-form DNA structures within its promoter. The conformational shift of this promoter between a transcription inactive form (G-quadruplex form) to an active one (a canonical double strand form) is strictly regulated by several nuclear proteins. In the second section I’ll present a study concerning the heterologous expression, the purification scheme of the resulting products and the biochemical characterization of the functional domains of human nucleolin, a nucleolar protein that is able to inhibit c-Myc oncogene transcription by a peculiar recognition of its promoter in a G quadruplex form. This approach was pursued to deeper clarify the mechanism of this binding event. Doubtless, this represents a promising goal in order to develop new selective and effective chemotherapy drugs.
Although revolutionary, the idea that genetic information was encoded only by DNA sequence, in a protein-free mechanism has been appeared definitely too simplistic. Indeed, in organisms with nuclei chromosomal DNA is organized along with protein templates (histones), forming a complex called chromatin. This is target of diverse array of posttranslational modifications that modulate the interaction among chromatin-associated proteins, which ultimately dictate dynamic transitions between transcriptionally active (euchromatin) or transcriptionally silent chromatin states (heterochromatin). In the last section, I will focus on the structural insights standing on the recognition event between a modified histone N-terminal tail and a specialized ‘effector’ protein (ORC1b), generally known for its role in pre-replication complex assembly.
The identification of the molecular details that clarify how distinct protein modules are able to recognize specific histone modifications is a critical step to understanding how chromatin dynamics influence fundamental DNA-templated processes such as transcription, DNA recombination and DNA repair. In particular, our results identify the tandem PHD-BAH domains of Arabidopsis thaliana ORC1b as a novel unmethylated-lysine-binding module, thereby establishing the first direct link between histone methylation grade and the epigenetic role of ORC1b, previously known as a transcriptional regulation factor only for a series of specific interactions with silencing regulators
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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