1,720,962 research outputs found
Investigating the role of extracellular matrix in regulating signaling pathways and embryonic development
Full text linkDuring my PhD I was involved in different projects exploiting the zebrafish animal model in order to analyse the role of extracellular matrix proteins in regulating signaling pathways.
In particular, in the first period of my PhD, I focused my attention on the in vivo function of Emilin3 in zebrafish animal model, with the aim of fully understanding the biological role of this extracellular matrix glycoprotein, both in embryonic development and in tissue homeostasis. In particular, I have contributed to in vivo studies, using several genetic approaches. These results demonstrated that Emilin3, a component of the peri-notochordal basement membrane, is required not only for the proper maturation of the notochord, but also for the regulation of Hedgehog signals derived from the notochord itself. Moreover, I also contributed to in vitro experiments that allowed us to understand how Emilin3 limits Hedgehog signals secreted by the notochord. We found that Emilin3 is able to interact with Scube2, a secreted factor that acts in a permissive way in the generation of Hedgehog ligand gradients. In this context, I generated several deletion constructs of Emilin3 and Scube2, which allowed us to determine the specific action of Emilin3, revealing that this extracellular matrix protein is able to interact with the EGF motifs of Scube2. Overall, this study revealed that the interaction between Emilin3 and Scube2 within the peri-notochordal basement membrane is essential for the proper notochord patterning activity. Such results were published in a full article in Development (Corallo et al., 2013). Alongside this work, my increasing interest on notochord patterning and functions led me to contribute to two review manuscripts on this subject (Corallo et al., Cell Mol Life Sci 2015; Corallo et al., J Cell Sci, in preparation).
Since the second year of my PhD, I independently started new functional studies in zebrafish focused on the role of Collagen VI during embryonic development. Mutations of Collagen VI genes in humans are causative for different forms of inherited muscle diseases, including Bethlem myopathy and Ullrich dystrophy. Previous work carried out in Collagen VI knockout (Col6a1–/–) mice revealed a crucial role for this extracellular matrix component in tissues homeostasis, and in particular in skeletal muscles, and demonstrated that ablation of Collagen VI has a remarkable impact on cell survival and organelle turnover. Indeed, these studies showed that collagen VI deficiency is causative for the myopatic syndrome of the mouse model and patients, characterized by spontaneous apoptosis, organelles alterations and deficient autophagy in muscle fibers. Although past work demonstrated that Collagen VI is broadly and dynamically expressed in a large number of tissues during embryonic development and postnatal life, no study until now ever assessed which roles Collagen VI plays during development and whether and how this major extracellular matrix component is regulating signaling pathways. Therefore, the aim of this part of my PhD work was to investigate which signaling pathways and tissues are affected by ablation of Collagen VI, in particular during embryonic development and using zebrafish as a model organism.
Towards this aim, I first carried out a characterization of the structure, organization and gene expression of Collagen VI chains in zebrafish. These information were the basis for further functional studies. By means of morpholino-mediated Collagen VI knockdown in different transgenic reporter zebrafish lines, I identified not only an alteration of muscle fibers development, but also an axonal growth defect of motor neurons in Collagen VI morphant embryos. In addition, knockdown of Collagen VI led to variations in Wnt and BMP signals during embryogenesis, thus suggesting a possible correlation between the developmental defects and the signaling pathway alterations caused by Collagen VI knockdown. Finally, I successfully applied the CRISPR/Cas9 technology for in vivo site-specific mutagenesis, generating a zebrafish col6a1 VI null line that represents a valuable tool for the thorough understanding of the functions of Collagen VI during development and in regulating signaling pathways
Role of the ECM in notochord formation, function and disease
No full textABSTRACT
The notochord is a midline structure common to all chordate animals; it provides mechanical and signaling cues for the developing embryo. In vertebrates, the notochord plays key functions during embryogenesis, being a source of developmental signals that pattern the surrounding tissues. It is composed of a core of vacuolated cells surrounded by an epithelial-like sheath of cells that secrete a thick peri-notochordal basement membrane made of different extracellular matrix (ECM) proteins. The correct deposition and organization of the ECM is essential for proper notochord morphogenesis and function. Work carried out in the past two decades has allowed researchers to dissect the contribution of different ECM components to this embryonic tissue. Here, we will provide an overview of these genetic and mechanistic studies. In particular, we highlight the specific functions of distinct matrix molecules in regulating notochord development and notochord-derived signals. Moreover, we also discuss the involvement of ECM synthesis and its remodeling in the pathogenesis of chordoma, a malignant bone cancer that originates from remnants of notochord remaining after embryogenesis.</jats:p
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
Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.
No full textVariations 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
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