1,720,966 research outputs found

    Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression

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    Parkinson's disease (PD) is characterized by the formation of intracytoplasmic inclusions, which contain alpha-synuclein (alpha-syn) protein. While most profound neurodegeneration is seen in the dopamine (DA) synthesizing neurons located in the ventral midbrain, it is unclear why some DA cell groups are more susceptible than others. In the midbrain, the degeneration of the substantia nigra (SN) DA neurons is severe, whereas the involvement of the ventral tegmental area (VTA) neurons is relatively spared. In the present study, we overexpressed human A53T alpha-syn in the VTA neurons and found that A53T toxicity did not affect their survival. There was, however, a mild functional impairment seen as altered open field locomotor activity. Overexpression of A53T in the SN, on the other hand, led to profound cell loss. These results suggest that the selective susceptibility of nigral DA neurons is at least in part associated with factor(s) involved in handling of alpha-syn that is not shared by the VTA neurons. Secondly, these results highlight the fact that impaired but surviving neurons can have a substantial impact on DA-dependent behavior and should therefore be considered as a critical part of animal models where novel therapeutic interventions are tested

    α-Synuclein expression is modulated at the translational level by iron

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    Several studies have suggested an interaction between a-synuclein protein and iron in Parkinson’s disease. The presence of iron together with a-synuclein in Lewy bodies, the increase of iron in the substantia nigra and the correlation between polymorphism of the several genes implicated in iron metabolism and Parkinson’s disease, support a role for iron in the neurodegeneration. Analysis of post mortem brains revealed increased amount of insoluble a-synuclein protein despite unchanged/reduced levels of a-synuclein mRNA in Parkinson’s disease. Interestingly, on the basis of the presence of a putative iron responsive element in the 5'-UTR, it has been suggested that there is a possible iron-dependent translational control of human a-synuclein mRNA. Considering the similarity between the sequences present in human a-synuclein mRNA and the ferritin iron responsive element, we postulated that iron deficiency would decrease the translation of a-synuclein mRNA. Here we used HEK293 cells treated with iron chelator deferoxamine or ferric ammonium citrate to verify the possible iron-dependent translational control of human a-synuclein biosynthesis. We show that the amount of polysome-associated endogenous human a-synuclein mRNA decreases in presence of deferoxamine. Our data demonstrate that human a-synuclein expression is regulated by iron mainly at the translational level. This result not only supports a role for iron in the translational control of a-synuclein expression, but also suggests that iron chelation may be a valid approach to control a-synuclein levels in the brain

    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
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