1,720,981 research outputs found
Implication de la protéine SV2A dans l'épilepsie: études précliniques
No full textThis PhD thesis deals with epilepsy and, in particular, with the role the Synaptic Vesicle 2A (SV2A) protein plays on the development and severity of this disease. Epilepsy is a group of neurodegenerative diseases whose most notable feature is the presence of spontaneous and recurrent brain seizures. Despite the extensive efforts made to treat epilepsy, 65 million people worldwide suffer from this disease. Moreover, with the available treatments, the seizures cannot be efficiently controlled in 30% of these patients. Amongst the antiepileptic drugs currently in use, levetiracetam is the one with the fewest side effects, easy to use, and a high efficacy controlling the seizures. These drugs typically target the SV2A protein, a transmembrane protein implicated in the synaptic transmission, and indispensable for life. In the existing literature on this topic, the homozygous mutation of SV2A has been associated with intractable epilepsy, growth retardation, and premature death both in mice and humans. However, to date, few studies have analysed the influence and the expression of this protein in the course of the epileptic process. Thus, the aim of this thesis is to further the understanding of the relationship between the SV2A protein and the epileptic disease, considering different perspectives and using diverse techniques. In the first part of this manuscript (Chapters 3 and 4), we study the variations in SV2A levels owing to the progression of temporal lobe epilepsy, making use of the kainic acid (KASE) rat model. In particular, Chapter 3 delves into the characteristics and the specificity of [18F]UCB-H, a radiotracer with an affinity for SV2A of 7.8 M (pIC50). On the one hand, we demonstrate the importance of high enantiomeric purity ((R)-enantiomer) and high affinity for the target (pIC50 > 6.8) to obtain PET images of good quality. On the other hand, we perform a competition assay between [18F]UCB-H and different SV2 ligands, demonstrating that this radiotracer displays more affinity for SV2A than for SV2B or SV2C, which are paralogs sharing around 60% of their sequences. In addition, in Chapter 3 we detail the methodology developed and validated to quantify the [18F]UCB-H uptake in the rat brain. The conclusion of this part is that it is possible to perform 60-minute dynamic scans (Vt) and 20-minute static scans (SUV20-40) with [18F]UCB-H. This methodology is applied in Chapter 4, where we analyse variations in SV2A levels with [18F]UCB-H in the KASE rat model, a well-known model of temporal lobe epilepsy (TLE). The results show a progressive increase in SV2A levels through the rat brain development. This increase is affected by the progression of epilepsy, as demonstrated by the significant group differences (Sham vs KASE) in all the phases of the disease. Moreover, these differences evolve progressively and differently in all brain regions. In addition, in Chapter 4 we also explore the relationship between variations in SV2A levels and other neuropathological correlates present in the epileptic process: the brain hypometabolism (quantified with [18F]FDG) and the severity of epilepsy (evaluated with electroencephalography). Our results propose that variations in SV2A levels could be: (1) positively correlated to a previous brain hypometabolism, and (2) positively correlated to the number of electrographic seizures observed in epileptic animals during the chronic phase of TLE.In the second part of this manuscript (Chapters 5 and 6) we assess the cognitive and behavioural impact of the decrease in SV2A expression in the brain, specifically in the hippocampus. Therefore, Chapter 5 is dedicated to the validation of a conditional SV2A knockout mice model (cKO) with [18F]UCB-H in vitro autoradiography. This model was developed with the Cre/loxP technique to study the influence of the specific decrease of SV2A expression in CA3 glutamatergic neurons in epilepsy. Then, in Chapter 6, we evaluate the cognitive and the behavioural aspects of this model with multiple tests (elevated plus maze, actometers, contextual fear conditioning test, and Barnes maze). The final goal of this evaluation is to shed light on the underlying molecular processes of the clinical features observed in the epileptic disease. Our results show a relationship between the decrease in SV2A expression at the hippocampus and the existence of anxiety-like features and spatial memory problems.Combined together, our findings represent a step forwards in the understanding, not only of the relationship between the SV2A protein and epilepsy, but also of the epileptic disease itself. Thus, with this work we expect firstly to further the existing knowledge about the underlying processes of epilepsy, and secondly to guide future researches, raising new key questions which may open the door to improve both the detection and treatment of epilepsy
Implication of the SV2A protein in epilepsy: preclinical studies/Implication de la prot\ue9ine SV2A dans l'\ue9pilepsie: \ue9tudes pr\ue9cliniques
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
No full textWe 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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