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    Striatal activity and synaptic features underlying dystonic muscle contraction

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    Resumo: A distonia é uma doença do movimento caracterizada por contrações musculares involuntárias e intermitentes, que levam a movimentos e posturas anormais. A distonia DYT1 é a forma hereditária mais comum e é causada por uma mutação no gene TOR1A. Apesar da sua causa genética bem definida, a distonia DYT1 apresenta uma baixa penetrância (~30%). Como resultado, surgiu o conceito de "second hit", sugerindo que fatores ambientais adicionais podem ser necessários para desencadear a manifestação da distonia. Embora tenham sido feitos progressos significativos na compreensão da distonia, a sua fisiopatologia exata ainda não está clara. Os gânglios da base, particularmente o estriado, desempenham um papel fundamental no controlo dos movimentos voluntários. Supõe-se que um desequilíbrio entre as vias direta e indireta possa levar às contrações musculares anormais. No entanto, os mecanismos subjacentes não são bem compreendidos. Alterações na plasticidade sináptica estriatal e na complexidade dendrítica dos MSNs foram relatadas em modelos animais de dystonia. No entanto, nenhum estudo examinou diferenças específicas entre as vias. Este projeto tem como objetivo determinar a plasticidade estrutural estriatal num modelo de ratinho de distonia DYT1, antes e 12 semanas após um "second hit" (compressão do nervo ciático) conhecido por induzir movimentos semelhantes à distonia. Utilizando imagens confocais de alta resolução, analisámos a morfologia dendrítica das D1-MSNs marcados com EYFP, por injeção retro-orbital de AAV9.Ef1.DIO.EYFP em ratinhos D1-Cre cruzados com ratinhos DYT1 e com os respectivos controlos (WT). As reconstruções 3D das imagens confocais dos D1-MSNs permitiram a quantificação detalhada dos parâmetros dendríticos, nomeadamente análise 3D de Sholl, o comprimento total das dendrites, o número de dendrites, os pontos de ramificação, a retilineidade e o volume do soma. Os nossos resultados mostram que, embora o efeito da mutação DYT1 na complexidade dendrítica não tenha atingido significância estatística, houve um aumento do volume do soma nos ratinhos DYT1 em comparação com os controlos WT, 12 semanas após a compressão do nervo ciático. Estes resultados sugerem que a disfunção da torsinaA, em combinação com um “second hit”, afeta a plasticidade estrutural das D1-MSNs. O nosso estudo fornece novas informações sobre as anomalias morfológicas nas D1-MSNs associadas à distonia DYT1.Abstract: Dystonia is a movement disorder characterized by involuntary and intermittent muscle contractions, leading to abnormal movements and postures. DYT-TOR1a dystonia (DYT1) is the most common hereditary form and it is caused by a mutation in the TOR1A gene. Despite its well-defined genetic cause, DYT1 dystonia exhibits low penetrance (~30%). As a result, the "secondhit" concept emerged, suggesting that additional environmental factors may be necessary to trigger the manifestation of dystonia. While significant progress has been made in understanding dystonia, its precise pathophysiology remains unclear. The basal ganglia, particularly the striatum, play a key role in controlling voluntary movements. It is hypothesized that an imbalance between the direct and indirect pathways may lead to the abnormal muscle contractions. However, the underlying mechanisms are not well understood. Changes in striatal synaptic plasticity and medium spiny neuron (MSN) dendritic complexity have been reported in animal models of dystonia. However, no studies have examined pathway-specific differences. This project aims to determine striatal structural plasticity in a mouse model of DYT1-Tor1A dystonia, before and 12 weeks after a “second-hit” (sciatic nerve crush) known to induce dystonia-like movements. Using high-resolution confocal imaging, we analyzed the dendritic morphology of D1-MSNs sparsely labeled with EYFP, by retro-orbital injection of AAV9.Ef1.DIO.EYFP in D1-Cre mice crossbred with DYT1 mice and wild-type littermates (WT). 3D reconstructions of D1-MSNs’ confocal images allowed for detailed quantification of dendritic parameters. Namely, 3D Sholl analysis, total dendritic length, number of dendrites, branching points, straightness, and soma volume. Our results show that, while an effect of the DYT1 mutation on dendritic complexity did not reach statistical significance, there was an increase in soma volume in DYT1 mice compared to WT controls, 12 weeks after a sciatic nerve crush. These findings suggest that torsinA dysfunction, in combination with a second-hit, affects the structural plasticity of D1-MSNs. Our study provides novel insights into the morphological abnormalities in D1- MSNs associated with DYT1 dystonia

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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

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    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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 Under Sail The Imagination of Jack London, 1893-1902

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    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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