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Investigating Enzyme Roles in Visual Chromophore Production Across Invertebrates and Vertebrates
The visual cycle, crucial for human vision, involves the recycling of the visual chromophore within the retina. This cycle enables us to process light and generate sight, granting humans and animals the ability to perceive their surroundings. Unfortunately, certain genetic conditions lead to visual diseases and loss of vision. Understanding the molecular mechanisms of key enzymes in this cycle, particularly those involved in visual chromophore production, has allowed scientists and clinicians to develop therapies aimed at preserving vision and managing these diseases. Conversely, a delayed understanding of key enzymes has inhibited the production of therapies. This thesis explores both vertebrate and invertebrate systems, particularly focusing on visual chromophore-producing enzymes to strengthen our understanding of the visual process across species.In animals, the retinal light response begins with the photoisomerization of the opsin-coupled 11-cis-retinaldehyde chromophore. This visual chromophore is enzymatically produced by carotenoid cleavage dioxygenases. In vertebrates, two such enzymes—β-carotene oxygenase 1 and retinal pigment epithelium 65 (RPE65)—convert carotenoid substrates into 11-cis-retinaldehyde. In contrast, invertebrates, such as insects, rely on a single enzyme, Neither Inactivation Nor Afterpotential B (NinaB), to perform this conversion. Both RPE65 and NinaB couple trans–cis isomerization with hydrolysis and oxygenation, respectively, but the detailed mechanism of their isomerase activities is still not fully understood. In this thesis, we present the structure of NinaB, shedding light on its active site and membrane-binding properties. Through structure-guided mutagenesis, we identify key residues in the substrate-binding cleft that regulate NinaB's isomerization activity. Our findings demonstrate that isomerization is mediated by distinct active site regions in NinaB and RPE65, providing a deeper understanding of the evolutionary convergence in visual system functions.
Another important enzyme in the visual cycle and retinoid processing in humans is lecithin:retinol acyl transferase (LRAT), which esterifies retinoids for storage in various tissues. While much is known about the enzymatic function of LRAT, there is still a lack of structural insight into this enzyme. Mutations in genes such as LRAT contribute to retinal diseases like retinitis pigmentosa (RP). Gaining a comprehensive structural understanding of LRAT could pave the way for therapeutic developments to treat such conditions. By exploring various biochemistry methods, we aim to enhance the current handling of the membrane protein LRAT for future studies.
Enzymes are typically classified into one of seven basic reaction classes, each corresponding to a specific type of chemical reaction. However, some enzymes catalyze multiple reaction types within a single active site. An example of this are isomerohydrolases and isomerooxygenases, which catalyze isomerization-coupled reactions essential for the production of 11-cis-retinoids, as mentioned above. In these enzymes, isomerization is coupled with other reactions, such as hydrolysis and oxygenation. A small number of enzymes exhibit similar coupled isomerization activities, some of which have been studied in detail. In an Appendix chapter, we also review these unique enzymes, exploring the structural and mechanistic basis of their reaction coupling, and revealing key catalytic commonalities that deepen our understanding of the visual cycle
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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