1,721,055 research outputs found
Phenotyping the serotonin transporter knockout rat: a behavioural, pharmacological and physiological approach. A new animal model of human serotonergic disorders.
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65625_phenthset.pdf (Publisher’s version ) (Open Access)
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71034.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 27 november 2008Promotor : Cools, A.R. Co-promotor : Ellenbroek, A.A.160 p
Factors contributing to the intake of alcohol and cocaine by rats: Role of genetic background, early-life events and stressors.
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27385.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit Nijmegen, 08 februari 2006Promotor : Cools, A.R. Co-promotor : Ellenbroek, A.A.163 p
Gene-environment interaction and intermediate phenotypes in alcohol dependence.
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91248.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 18 oktober 2011Promotores : Jong, C.A.J. de, Buitelaar, J.K. Co-promotores : Ellenbroek, A.A., Verkes, R.J.247 p
Neurobiological mechanisms underlying individual differences in responses to addictive drugs in rats: with special focus on dopamine.
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51889.pdf (Publisher’s version ) (Open Access)This thesis addresses the intriguing question why some individuals easily become addicted to drugs, while others do not. A key player in this phenomenon is the neurotransmitter dopamine. Several studies have indicated that there are differences in the dopaminergic system of rats that are more or less prone to addiction. In this thesis we describe neurobiological differences in the dopaminergic system of the so-called apomorphine-susceptibe (APO-SUS) and unsusceptible (APO-UNSUS) rats. These rats have a different vulnerability to the dopamine D2 agonist apomorphine and show behavioural, physiological, endocrinological and genetical differences. Most importantly, they show a difference in drug self-administration (alcohol, cocaine) and drug sensitivity. The aim of this thesis was to investigate the neurobiological differences between these two rat lines that might underlie their difference in drug sensitivity. Thus, two types of research were conducted. First, the dopaminergic system was investigated using in vivo microdialysis, measuring extracellular levels of dopamine, and in vitro immunocytochemistry for the enzyme tyrosine hydroxylase (TH), which is the rate-limiting enzyme in dopamine synthesis. Second, the response of the dopaminergic system to in vivo administration of amphetamine and cocaine was investigated with prepulse inhibition as read-out parameter. The main finding of these studies was that there are pronounced differences in the basic structure of the dopaminergic system between APO-SUS and APO-UNSUS rats. In addition, the response of their dopaminergic system to environmental and drug challenges was different. Finally, the underlying cellular mechanism that mediates the response to amphetamine was also different between the rat lines. In conclusion, individuals that have a different drug sensitivity have a different make-up of the dopaminergic system and this system also responds differently to environmental and drug challenges. Thus, addiction has a clear neurobiological basis that awaits further investigation in order to understand the mechanisms underlying individual differences in drug sensitivity.RU Radboud Universiteit Nijmegen, 10 januari 2007Promotor : Cools, A.R. Co-promotor : Ellenbroek, A.A.160 p
Molecular understanding of a rat model with schizophrenia-related features. Gene-dosage imbalance of the gamma-secretase component Aph-1b in APO-SUS and -UNSUS rats
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30145.pdf (Publisher’s version ) (Open Access)Wistar rats pharmacogenetically selected for a high susceptibility to the dopamine agonist apomorphine (APO-SUS rats) display many differences with their phenotypic counterpart (APO-UNSUS rats), which are remarkably similar to those observed in schizophrenic patients. In this thesis we tried to understand the molecular mechanism underlying the APO-SUS/-UNSUS complex phenotype, which might aid in finding the cause of schizophrenia in human. Microarray expression analyses revealed in APO-SUS rats, relative to -UNSUS rats, a reduced expression of Aph-1b, a component of the gamma-secretase enzyme complex that is involved in multiple (neuro)developmental signalling pathways. These differences were caused by different gene copy numbers; APO-SUS rats harbour only one or two gene copies of Aph-1b, whereas APO-UNSUS rats contain three copies. This gene-dosage imbalance was caused by an unequal crossing-over event involving a segmental duplication within the Aph-1b locus. Although the expression levels of the other gamma-secretase components were not different, the gamma-secretase cleavage activity towards several substrates was affected and the Aph-1b genotypes segregated with a number of behavioural phenotypes. Through crossing and genetic re-selection, new rat lines were generated with one, two or three Aph-1b gene copies against otherwise similar genetic backgrounds. These rats revealed, next to affected Aph-1b expression levels throughout development, temporal, tissue- and substrate-specific changes in gamma-secretase cleavage activity. Preliminary studies on transgenic Xenopus laevis expressing Aph-1a under control of the proopiomelanocortin promoter, imply that the manipulation of Aph-1 expression in Xenopus melanotrope cells leads to a modified sensitivity of the dopaminergic system. In conclusion, these studies suggest that a subtle change in the expression of a (neuro)developmentally important protein may spatio-temporally affect diverse signalling pathways, ultimately resulting in a complex phenotype that is generally thought to be caused by multiple affected genes. Furthermore, we implicate the possible involvement of the gamma-secretase enzyme in complex disorders, like schizophrenia.RU Radboud Universiteit Nijmegen, 22 december 2006Promotores : Martens, G.J.M., Cools, A.R. Co-promotor : Ellenbroek, A.A.160 p
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
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