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Expression and functional role of Emilin-3, a peculiar member of the Emilin/Multimerin family
Full text linkEmilin-3 is a glycoprotein of the extracellular matrix belonging to a family of proteins that contain a characteristic N-terminal cystein-rich region, the EMI domain. Knockout mice for Emilin-1, the prototypic protein of the family, display hypertension and reduced diameter of blood vessels due to increased bioavailability of active TGF-β1 that reduces the proliferation rate of vascular smooth muscle cells. This finding is in agreement with the distribution of Emilin-1, which is mainly present in the cardiovascular system. In vitro studies demonstrated that Emilin-1 through its EMI domain acts as an extracellular inhibitor of TGF-β1 processing. At difference from other emilins/multimerins, Emilin-3 has a unique protein structure, lacking the C-terminal C1q domain. Emilin-3 has a peculiar pattern of expression, as revealed by our studies in mouse and zebrafish. The gene is not expressed in the cardiovascular system, while it is present in tissues playing key roles during the development. Emilin-3 mRNA is abundant in the tail bud, notochord and chordoneural hinge, in the subventricular zone of the midbrain, around the osteogenic mesenchyme and in the developing gonads. In the perspective of studying Emilin-3 properties and unveiling its function, in this PhD work I carried out different in vitro and in vivo studies. In summary, the data reported in this thesis provide the first detailed characterization, with both structural and functional insights, of the extracellular glycoprotein Emilin-3.Emilina-3 è una glicoproteina della matrice extracellulare appartenente ad una famiglia di proteine caratterizzate dalla presenza nella loro porzione N-terminale di un domino ricco di cisteine, il dominio EMI. Topi knockout per Emilina-1, la proteina capostipite di questa famiglia, presentano ipertensione arteriosa e una riduzione del calibro dei vasi sanguigni, alterazioni che sono state attribuite ad una disregolazione del signaling del TGF-β. Queste osservazioni sono in accordo con la distribuzione proteica di Emilina-1, che è abbondantemente presente a livello del sistema cardiovascolare. Esperimenti in vitro hanno dimostrato che Emilina-1, attraverso il suo dominio EMI, agisce come inibitore extracellulare della maturazione del precursore del TGF-β in citochina matura. Emilina-3 possiede una peculiare struttura proteica in quanto è priva del dominio gC1q al suo C-terminale, che è invece presente in tutte le altre Emiline/Multimerine. Inoltre Emilina-3 presenta anche un pattern di espressione unico, come dimostrato con i nostri studi di espressione in topo e zebrafish. Il gene infatti non è espresso nel sistema cardiovascolare come gli altri geni della famiglia, ma è espresso durante la vita embrionale in distretti importanti per i processi di sviluppo. Il messaggero di Emilina-3 è abbondante nel tail bud, nella cerniera cordoneurale, nella zona subventricolare del mesencefalo, nel pericondrio delle ossa lunghe in formazione e nei primordi delle gonadi. Con la finalità di studiare le caratteristiche e la funzione di Emilina-3, durante il mio ciclo di dottorato ho intrapreso diversi studi sia in vitro che in vivo. In conclusione, gli esperimenti riportati in questa tesi rappresentano la prima descrizione della glicoproteina Emilina-3, sia dal punto di vista strutturale che funzionale
Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.
No full textEMILIN2 down-modulates the Wnt signalling pathway and suppresses breast cancer cell growth and migration.
No full textTargeting of EMILIN-1 and EMILIN-2 to Fibrillin Microfibrils Facilitates their Incorporation into the Extracellular Matrix
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Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI deficient muscles.
No full textAutophagy is a catabolic process that provides the degradation of altered/damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagic flux is fundamental for the homeostasis of skeletal muscles in physiological conditions and in response to stress. Defective as well as excessive autophagy is detrimental for muscle health and has a pathogenic role in several forms of muscle diseases. Recently, we found that defective activation of the autophagic machinery plays a key role in the pathogenesis of muscular dystrophies linked to collagen VI. Impairment of the autophagic flux in collagen VI null (Col6a1–/–) mice causes accumulation of dysfunctional mitochondria and altered sarcoplasmic reticulum, leading to apoptosis and degeneration of muscle fibers. Here we show that physical exercise activates autophagy in skeletal muscles. Notably, physical training exacerbated the dystrophic phenotype of Col6a1–/– mice, where autophagy flux is compromised. Autophagy was not induced in Col6a1–/– muscles after either acute or prolonged exercise, and this led to a marked increase of muscle wasting and apoptosis. These findings indicate that proper activation of autophagy is important for muscle homeostasis during physical activity
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
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