1,720,966 research outputs found

    Redox proteomics analysis of 4-hydroxynonenal-modified proteins in brain from Down Syndrome

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    Down syndrome (DS) is the most common genetic cause of intellectual disability, due to partial or complete triplication of chromosome 21 (Chr21). DS subjects are characterized by a number of abnormalities including mental retardation, premature aging and development of Alzheimer’s-like dementia after 40 years. Several studies showed that oxidative stress play a crucial role in the development of neurodegeneration in DS. Increased lipid peroxidation is one of the main events causing redox imbalance within cells through the formation of toxic aldehydes that easily react with DNA, lipid and proteins. In this study we used a redox proteomics approach to identify specific target of 4-hydroxynonenal modification in the frontal cortex from DS (under the age of 40, DSyg) and DS-AD (over the age of 40) subjects compared with age-matched controls. Our results show that increased oxidation of specific protein occurs already in DS yg and further progress in DS/AD subjects. In particular, a group of these proteins follow a specific pattern of oxidation in DS yg vs CTR yg as characteristic features of DS phenotype; a second group show increased oxidation from DS yg to DS/AD, thus possibly playing a role in the development of AD-like dementia. Oxidized protein are involved in important biological functions including intracellular quality control system, energy metabolism and antioxidant response. In conclusion, our results show that oxidative damage is an early event in DS, as well as dysfunctions of protein degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to accumulate oxidative damage which might contribute to AD development

    Pathological role of PI3K/AKT/mTOR signaling pathway in Down Syndrome brain

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    Down syndrome (DS) is the most frequent chromosomal abnormality that causes intellectual disability. The neuropathology of DS is complex and includes development of Alzheimer disease (AD). The accumulation of amyloid beta (Aβ)-peptide in DS brain can be observed as early as 8–12 years of age. Interestingly, the incidence of dementia typically does not increase until adults with DS are over the age 50 years. Within this context, it has been suggested that DS may serve as a model for the study the early molecular events in the pathogenesis and progression of AD neuropathology. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of AD-like dementia. In particular we focused our work on the evaluation of PI3K/Akt/mTOR axis in the frontal cortex from DS subjects (under the age of 40 ) and DS with AD compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis control several key pathways involved in DS neuropathology and progression to AD and, if aberrantly regulated, affect Aβ deposition and tau phosphorylation

    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

    Neuropathological role of pi3k/akt/mtor axis in Down syndrome brain

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    Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aβ) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS

    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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