1,721,041 research outputs found
SYNAPSE AND DENDRITE DEFICITS INDUCED BY MUTATIONS IN THE X-LINKED INTELLECTUAL DISABILITY GENE IL1RAPL1
Full text linkDoctorial Thesis of Caterina Montani:
Synapse and dendrite deficits induced by mutations in the X-linked intellectual disability gene Il1rapl1
ABSTRACT
Mutations and deletions of Interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene, localized on X chromosome, are strongly associated to intellectual disability (ID) and autism spectrum disorder (ASD) (Carrie et al., 1999; Piton et al., 2008). IL1RAPL1 protein is localized at the postsynaptic compartment of excitatory synapses (Pavlowsky et al.) and plays an important role in synapse formation and stabilization in developing brain, via the interaction with other pre- and post-synaptic proteins (Pavlowsky et al., ; Valnegri et al.).
Several studies indicate that ID and ASD are associated with abnormalities of dendrites and dendritic spines morphology (Verpelli et al.), resulting in a defect in neuronal connectivity and thus an altered processing of information at both the cellular and the neural network. Thus, the analysis of IL1RAPL1 function will contribute to identify the molecular and cellular mechanisms that contribute to cognitive brain function.
The aim of presented work was to characterize IL1RAPL1 mutants identified in patients with ID and ASD and to perform a behavioral and neuronal morphology analysis on IL1RAPL1 KO mice.
In particular, we studied the function of three novel independent mutations of IL1RAPL1 gene in patients presenting mild to moderate ID (Ramos-Brossier et al.): IL1RAPL1∆exon6, IL1RAPL1 C31R and IL1RAPL1 I643V. Through over-expression of the IL1RAPL1 mutants in rat primary cultured neurons, we studied their localization, the ability to recruit presynaptic compartment and to induce changes in neuronal morphology and spine density. To better understand the molecular interaction between IL1RAPL1 and PTPδ, we also investigate, through a cell aggregation assay, the residual ability of IL1RAPL1 mutants to bind PTPδ (Ramos-Brossier et al.).
We found that two of the studied mutants lead to a partial loss of function of IL1RAPL1 protein, which is, first, responsible for the cognitive impairments observed in patients and, second, highlights the important function of the extracellular domain for the trans-synaptic PTPδ/IL1RAPL1 interaction in synaptogenesis (this part of the data has already been published (Ramos-Brossier et al.) thus the results and their discussion are not fully reported in this Thesis). Because dendritic abnormalities are one of the most consistent anatomical correlates of ID, we also charactrize the role of wild type and mutants IL1RAPL1 in regulating dendrite morphology using both in vitro neuronal cultures and IL1RAPL1 KO mice.
We measured dendritic branching complexity of hippocampal CA1, CA2 and cortex neurons of WT and IL1RAPL1 KO mice. Interestingly we found, associated to hippocampal cognitive impairment, an increased number of dendrite branching in CA1 and CA2 hippocampal neurons but not in cortex of IL1RAPL1 KO mice. In transfected hippocampal neurons the over-expression of full length IL1RAPL1 protein and mutants lacking part of C-terminal domains leads to a simplification of neuronal arborisation. This effect is instead abolished when we overexpressed mutants lacking part of N-terminal domains. Thus our results indicate the importance of IL1RAPL1 extracellular domains not only in synaptogenesis but also in dendrite development. However we also found that for this activity PTPδ interaction is not required suggesting that an unknown IL1RAPL1 binding partner is involved in the effect on dendrite morphology.
Understanding how mutations or absence of IL1RAPL1 act on synaptogenesis and dendritic morphology can help to clarify how any changes in IL1RAPL1 function lead to cognitive disorders in humans. In addition, further investigation of the molecular mechanism of IL1RAPL1 would identify potential drug targets to ameliorate cognitive deficits in patients
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
La Cattedrale di Pisa nella Piazza dei Miracoli
No full textSulla base di precedenti sperimentazioni eseguite in piazza dei Miracoli tra il 2002 e il 2003, nel Battistero e nella zona absidale, il progetto è iniziato nel 2005 dal rilievo del volume esterno delle architetture di piazza dei Miracoli al fine di ottenere un innovativo data base integrato. L’utilizzo della tecnologia di scansione laser a tempo di volo per realizzare un modello tridimensionale dell’esterno del Duomo di Pisa tende a sviluppare il collegamento con i Sistemi Informativi relativi alla documentazione storica e di restauro già esistenti o in corso di definizione, in collaborazione con l’ISTI–CNR di Pisa. Il rilievo realizzato del Duomo e della Piazza costituisce la base essenziale di una banca dati di tipo dinamico nella quale inserire le informazioni di tipo storico-culturale, diagnostico e, in generale, sullo stato conservativo attuale e passato del bene. Il rilievo tridimensionale costituisce elemento essenziale per la localizzazione e la mappatura di un bene nonché di ogni elemento e particolare di cui esso è costituito essendo la conoscenza geometrica il fondamento per gli interventi finalizzati alla diagnosi, al monitoraggio e alla tutela. La costruzione di modelli digitali tridimensionali permette quindi una facile integrazione con dati di tipo strutturale ed eventualmente colorimetrico per una completa rappresentazione del bene in oggetto
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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