1,720,977 research outputs found
Investigating the role of Emilin3, an extracellular matrix protein of the Emilin/Multimerin family
Full text linkEmilin3 is an extracellular matrix molecule belonging to the EMILIN/Multimerin family. Emilin1, the founding member of this family, was originally identified as a glycoprotein particularly abundant in blood vessels, where it was found to be associated with elastic fibers. Whether Emilin3 is also associated with elastic fibers is still unknown. Differently from Emilin1 and all the other members of the family, Emilin3 is not expressed in the cardiovascular system, as shown by our studies both in mouse and zebrafish.
The main focus of my PhD study was to elucidate the function of Emilin3 during embryonic development, using zebrafish as a model. The two zebrafish Emilin3 paralog genes, emilin3a and emilin3b, are dynamically expressed in the tail bud, in the chordoneural hinge, and in the notochord during early zebrafish development. By using a novel specific antibody, I found that Emilin3 is deposited in the notochord sheath, a specialized extracellular matrix structure that surrounds the notochord. Morpholino-mediated knockdown of both Emilin3 paralogs led to a marked distortion of the notochord, as a consequence of structural defects of the notochord sheath. Besides its structural role, the notochord has also an important patterning activity, a process that is mainly mediated by the secretion of Hedgehog (Hh) ligands. Notably, the patterning activity of the notochord is also affected by Emilin3, as revealed by increased Hh signaling in Emilin3 depleted embryos and decreased Hh signaling in embryos overexpressing Emilin3 in notochord cells. Mechanistically, in vitro and in vivo experiments showed that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2. Altogether, these findings indicate that Emilin3 has an essential role for the proper structure and function of the developing notochord.
During my PhD, I also investigated the distribution pattern of Emilin3 in mouse tissues. Taking advantage of specific antibodies, I investigated and compared the distribution of different Emilin proteins in mouse tissues. The data show that, similarly to what I observed in zebrafish, Emilin3 has the most restricted tissue distribution. The elucidation of Emilin3 distribution in embryonic and adult tissues was also crucial for starting, during the very last part of my PhD, the phenotypic characterization of Emilin3 knockout mice, which were previously generated in our lab. I found that Emilin3 knockout mice display a decreased body weight gain and an increased mortality during the first four weeks after birth. Microscope analysis revealed strong structural abnormalities of hair follicles within the first catagen/telogen transition. These findings point at a role for Emilin3 in hair follicle maturation, and are the basis for future studies aimed at the full understanding of the role of Emilin3 in embryonic and postnatal development and in tissue homeostasi
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
Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.
No full textThe zebrafish as a model for studying neuroblastoma
Full text linkNeuroblastoma is a tumor arising in the peripheral sympathetic nervous system and is the most common cancer
in childhood. Since most of the cellular and molecular mechanisms underlying neuroblastoma onset and progression
remain unknown, the generation of new in vivo models might be appropriate to better dissect the peripheral
sympathetic nervous system development in both physiological and disease states. This review is focused on the use
of zebrafish as a suitable and innovative model to study neuroblastoma development. Here, we briefly summarize the
current knowledge about zebrafish peripheral sympathetic nervous system formation, focusing on key genes and cellular
pathways that play a crucial role in the differentiation of sympathetic neurons during embryonic development.
In addition, we include examples of how genetic changes known to be associated with aggressive neuroblastoma
can mimic this malignancy in zebrafish. Thus, we note the value of the zebrafish model in the field of neuroblastoma
research, showing how it can improve our current knowledge about genes and biological pathways that contribute
to malignant transformation and progression during embryonic life
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
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