1,721,128 research outputs found
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
Dysfunctions of the endo-lysosomal pathway : from Down syndrome to Alzheimer’s disease
No full textL’élargissement des endosomes précoces (EP) a été amplement décrit dans la trisomie 21 (T21) et la maladie d’Alzheimer (MA). La présence d’EP élargis a été démontrée dans des neurones avant même le développement de la neuropathologie et des symptômes de la MA. L’élargissement des EP a également été identifié dans de nombreux modèles de MA et de T21. Il a été proposé que la surexpression d’APP induise l’élargissement des EP, mais certaines observations suggèrent une origine multifactorielle à l’élargissement des EP. Malgré la petite taille des EP, leur morphologie n’a jamais été analysée à haute résolution. Dans cette étude, nous caractérisons les EP et la voie endosomale dans la T21 afin de mieux en comprendre les phénotypes et les mécanismes moléculaires associés. Grâce à différentes méthodes de microscopie électronique et super-résolutive, nous observons dans de nombreux modèles de T21 une augmentation du nombre d’EP de taille normale ayant tendance à s’agréger plutôt que des EP élargis. Nous montrons que le recyclage du récepteur à la transferrine est augmenté alors que la dégradation du récepteur à l’EGF est ralentie. Nous montrons ensuite que les niveaux de Rab5 et de PI(3)P sont augmentés et le niveau d’EEA1 est diminué. Enfin, l’inhibition de la kinase PIKfyve permet de rétablir le niveau d’EEA1 et la production d’Aβ dans des fibroblastes T21. Notre étude redéfinit les phénotypes de la voie endo-lysosomale dans la T21 aux niveaux morphologiques, dynamiques et moléculaires. Ces résultats apportent de nouvelles hypothèses mécanistiques pour expliquer les anomalies endosomales dans la T21 et la MA.Abnormal early endosome (EE) enlargement was widely characterized in the brain of individuals with Down syndrome (DS) and Alzheimer’s disease (AD) patients. Neurons bearing enlarged EE have been described before the development of the neuropathological hallmarks and clinical symptoms of AD. EE enlargement was also detected in various models of AD and DS. It was proposed that APP overexpression would lead to EE enlargement, but several lines of evidence rather suggest multifactorial causes to EE enlargement. Despite the nanometric size range of EE, this phenotype was never quantified with high resolution microscopy. Here, we characterize EE and the endo-lysosomal pathway in DS in order to better understand endosomal phenotypes and their underlying molecular mechanisms. With electron microscopy technics and super-resolution, we observe an increased number of normal-sized EE with a tendency to clustering rather than enlarged EE in various DS models. We show that the transferrin receptor recycling is accelerated, while t573.84he degradation of the EGF receptor is delayed. Then, we show that the levels of Rab5 and PI(3)P are decreased but the level of EEA1 is increased. Finally, the inhibition of the PIKfyve kinase rescues the level of EEA1 and Aβ production in fibroblasts from individuals with DS. Our study redefines phenotypes of the endo-lysosomal pathway in DS, at morphological, dynamic and molecular levels. These results provide new hypotheses to explain endosomal abnormalities in DS and AD, and bring insights into the comprehension of the role the endo-lysosomal pathway in both pathologies
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
Characterization of the cholesterol binding site on the APP : a modulator of the secretion of amyloïd peptides
No full textLa maladie d’Alzheimer (MA) se caractérise par une perte mnésique progressive. La quantité de cholestérol est plus élevée dans les cerveaux de patients atteints de la MA. De plus, l’existence d’un site de liaison entre le cholestérol (SLC) et l’Amyloid Precursor Protein (APP) a été démontrée par résonance magnétique nucléaire. Les mutations effectuées dans le SLC de l’APP abolissent totalement l’interaction entre les peptides et des liposomes chargés en cholestérol. Tous les mutants du SLC produisent beaucoup moins d’Aβ40 et Aβ42 sans modifier les produits de clivage de l’APP. Nous avons mis en évidence deux catégories de mutations : les mutations juxtamembranaires qui augmentent la sécrétion de fragments courts d’Aβ et les mutations transmembranaires, incluant la mutation familiale italienne, qui diminuent la sécrétion de peptides courts d’Aβ. Ces résultats suggèrent un décalage du clivage des mutants par la γ-sécrétase et/ou une modification de sa processivité conduisant à la formation de peptides de courtes tailles. Parallèlement, nous avons montré que des cultures primaires de neurones exprimant l’ApoE4 sécrètent en plus grande quantité les peptides amyloïdes Aβ38, 40 et 42 comparé à des neurones exprimant l’ApoE3. Les neurones ApoE4 expriment plus fortement les protéines tau et phospho-tau, mais plus faiblement l’ApoE « full lenght » par rapport aux neurones ApoE3. Le SLC et le génotype ApoE4 contribuent donc à l’augmentation de la sécrétion de peptides amyloïdes. Il serait intéressant de connaître les mécanismes cellulaires impliquant le SLC de l’APP, le cholestérol et son transporteur l’ApoE.Alzheimer’s disease (AD) is characterized by progressive loss of memory. The amount of cholesterol is higher in the brains of patients with AD. In addition, the existence of a cholesterol binding site (CBS) on APP sequence was demonstrated by nuclear magnetic resonance. Mutations in the CBS of APP completely abolish the interaction between peptides and liposomes loaded with cholesterol. All CBS mutants produce much less Aβ40 and Aβ42 when expressed in HEK293T cells without altering the other APP cleavage products. We identified two mutations: juxtamembrane mutations that increase the secretion of short fragments of Aβ and transmembrane mutations, including the Italian family mutation, which decrease the secretion of short Aβ peptides. These results suggest a shift in the cleavage of mutants by γ-secretase and / or a modification of its processivity leading to the formation of short peptides. Thus, the CBS is a key actor in the secretion of amyloid peptides. At the same time, we have shown that primary cultures of ApoE4-expressing neurons secrete amyloid peptides Aβ38, 40 and 42 in greater quantities compared to neurons expressing ApoE3. ApoE4 neurons express more strongly the tau and phospho-tau proteins, but more weakly the ApoE "full lenght" protein compared to the ApoE3 neurons. The CBS and the ApoE4 genotype therefore contribute to the increase of the amyloid peptides secretion. It would be interesting to know the cellular mechanisms involving the CBS of APP, cholesterol and its carrier ApoE
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
Analysis of Proteins at the Single Cell Level
Get PDFProteins bring a consequent additional level of information in comparison with nucleic acids on a cell's state as proteins are dynamically processed and chemically modified in the cell as a function of the cell life. Yet, the analysis of proteins is challenging as no amplification step is possible as is the case for nucleic acids, and another difficulty lies in the dynamic range of protein expression in a single sample (e.g. a single cell). While the same challenges are still found for microfluidic-based analysis of proteins, microsystems bring about enhanced analytical performance and novel analysis opportunities. This is illustrated here for two different strategies that can be adopted for protein analysis in a chip format. A first strategy consists of transposing the standard proteomic protocol in miniaturized analytical tools, and this provides a number of advantages and enhancement for the analysis: an overall improvement is expected when using smaller systems whose capacity matches better the size of the samples; sample manipulation is minimized when using LOC technology, and this goes together with a decrease in sample loss and contamination; enhanced analytical performance in terms of analysis time and detection sensitivity is ensured by micro- and nano-scale features; last, the use of microfabricated structures guarantees higher analysis reproducibility. In a second strategy, the analysis is actually performed at the single cell level. This strategy does not enable protein mapping anymore, but the investigation focuses on given proteins (a single protein of a small number thereof) which are specifically targeted. For that purpose, innovative microfluidic-based protocols have been developed, and we classify them in three categories of fully destructive, partially invasive and non invasive protocols. Ongoing developments in the area of nanotechnology would enable truly protein mapping at the single cell level, with the use of nanofabricated tools in a LOC platform</jats:p
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