In vitro studies of te novel protein Q7: role on hyaluronian regulation in breast tumor microenvironment

Cancer is a group of multifactorial diseases, which involves variations in multiple genes, often coupled with environmental causes. It is characterized by uncontrolled growth of cells that are able to divide continually and invade into surrounding tissues. In Italy, breast cancer is the most common cancer form among women, accounting for over 20% of the cancer cases and about 15% of the mortality (Jemal et al., 2011). Dysregulation of the composition of the extracellular matrix (ECM) is associated with cancer, by facilitating cell growth, survival and invasion. Among various ECM glycosaminoglycans, hyaluronan (HA) has a remarkable structural importance but also a role in regulating cellular processes through a binding with membrane receptors and activation of signalling pathways. The role of HA in tumour cells’ functions depends on its molar mass which is regulated by the enzymes that synthesize HA, i.e. hyaluronan synthases (HAS), and hyaluronidases (HYALs). Alterations of these metabolic enzymes are correlated with breast cancer progression. In this thesis, we aimed to explore the role of crosstalk between tumour cells and stroma, focusing our attention to the HA regulation. Specifically, we studied the mechanism by which proteins secreted by breast tumour cells alter HA metabolizing enzymes and its synthesis in the stromal cells. Recently, in our laboratory we discovered a new protein in the conditioned medium (CM) of a breast tumour cell line, called “Uncharacterized protein of c10orf118” or “Q7z3e2”. For simplicity, this protein is called “Q7”. Further studies on the two well-known breast cancer cell lines MCF-7 (low invasive cells) and MDA-MB231 (high invasive cells) demonstrated a higher expression and secretion of Q7 in tumour cells than in normal cells. Information obtained from bioinformatics databanks (the Ensemble website) showed that the gene for Q7 is located on human chromosome 10 in the region q25.3. The gene is composed of 18 exons and there are six splicing variants, but only four of them code for proteins. The secreted isoform found in the CM of breast cancer cell lines is the full-length isoform that consists of 898 aminoacids and has a molecular weight of 104 kDa. In the literature and in our data, it was shown that co-culture of breast cancer cells with fibroblasts results to an induction of HAS2 in fibroblasts and an increase of the secreted HA. Among the three HASes, HAS2 isoform was the most expressed and induced by breast tumour cells CM in fibroblasts, whereas HAS1 was not detected. When fibroblasts were treated with CM from MCF-7 cells, in the absence of Q7, the relative expression of HAS2 was significantly decreased. This last data was further confirmed when fibroblasts were treated with a recombinant protein of Q7 and a HAS2 induction and HA increase were observed. To sum up, the data of this thesis demonstrate that the novel protein Q7 may play a key role in the increment of pericellular HA and in the breast tumour progression

In vitro studies of te novel protein Q7: role on hyaluronian regulation in breast tumor microenvironment

Cancer is a group of multifactorial diseases, which involves variations in multiple genes, often coupled with environmental causes. It is characterized by uncontrolled growth of cells that are able to divide continually and invade into surrounding tissues. In Italy, breast cancer is the most common cancer form among women, accounting for over 20% of the cancer cases and about 15% of the mortality (Jemal et al., 2011). Dysregulation of the composition of the extracellular matrix (ECM) is associated with cancer, by facilitating cell growth, survival and invasion. Among various ECM glycosaminoglycans, hyaluronan (HA) has a remarkable structural importance but also a role in regulating cellular processes through a binding with membrane receptors and activation of signalling pathways. The role of HA in tumour cells\u2019 functions depends on its molar mass which is regulated by the enzymes that synthesize HA, i.e. hyaluronan synthases (HAS), and hyaluronidases (HYALs). Alterations of these metabolic enzymes are correlated with breast cancer progression. In this thesis, we aimed to explore the role of crosstalk between tumour cells and stroma, focusing our attention to the HA regulation. Specifically, we studied the mechanism by which proteins secreted by breast tumour cells alter HA metabolizing enzymes and its synthesis in the stromal cells. Recently, in our laboratory we discovered a new protein in the conditioned medium (CM) of a breast tumour cell line, called \u201cUncharacterized protein of c10orf118\u201d or \u201cQ7z3e2\u201d. For simplicity, this protein is called \u201cQ7\u201d. Further studies on the two well-known breast cancer cell lines MCF-7 (low invasive cells) and MDA-MB231 (high invasive cells) demonstrated a higher expression and secretion of Q7 in tumour cells than in normal cells. Information obtained from bioinformatics databanks (the Ensemble website) showed that the gene for Q7 is located on human chromosome 10 in the region q25.3. The gene is composed of 18 exons and there are six splicing variants, but only four of them code for proteins. The secreted isoform found in the CM of breast cancer cell lines is the full-length isoform that consists of 898 aminoacids and has a molecular weight of 104 kDa. In the literature and in our data, it was shown that co-culture of breast cancer cells with fibroblasts results to an induction of HAS2 in fibroblasts and an increase of the secreted HA. Among the three HASes, HAS2 isoform was the most expressed and induced by breast tumour cells CM in fibroblasts, whereas HAS1 was not detected. When fibroblasts were treated with CM from MCF-7 cells, in the absence of Q7, the relative expression of HAS2 was significantly decreased. This last data was further confirmed when fibroblasts were treated with a recombinant protein of Q7 and a HAS2 induction and HA increase were observed. To sum up, the data of this thesis demonstrate that the novel protein Q7 may play a key role in the increment of pericellular HA and in the breast tumour progression

In vitro studies of te novel protein Q7: role on hyaluronian regulation in breast tumor microenvironment

Cancer is a group of multifactorial diseases, which involves variations in multiple genes, often coupled with environmental causes. It is characterized by uncontrolled growth of cells that are able to divide continually and invade into surrounding tissues. In Italy, breast cancer is the most common cancer form among women, accounting for over 20% of the cancer cases and about 15% of the mortality (Jemal et al., 2011). Dysregulation of the composition of the extracellular matrix (ECM) is associated with cancer, by facilitating cell growth, survival and invasion. Among various ECM glycosaminoglycans, hyaluronan (HA) has a remarkable structural importance but also a role in regulating cellular processes through a binding with membrane receptors and activation of signalling pathways. The role of HA in tumour cells’ functions depends on its molar mass which is regulated by the enzymes that synthesize HA, i.e. hyaluronan synthases (HAS), and hyaluronidases (HYALs). Alterations of these metabolic enzymes are correlated with breast cancer progression. In this thesis, we aimed to explore the role of crosstalk between tumour cells and stroma, focusing our attention to the HA regulation. Specifically, we studied the mechanism by which proteins secreted by breast tumour cells alter HA metabolizing enzymes and its synthesis in the stromal cells. Recently, in our laboratory we discovered a new protein in the conditioned medium (CM) of a breast tumour cell line, called “Uncharacterized protein of c10orf118” or “Q7z3e2”. For simplicity, this protein is called “Q7”. Further studies on the two well-known breast cancer cell lines MCF-7 (low invasive cells) and MDA-MB231 (high invasive cells) demonstrated a higher expression and secretion of Q7 in tumour cells than in normal cells. Information obtained from bioinformatics databanks (the Ensemble website) showed that the gene for Q7 is located on human chromosome 10 in the region q25.3. The gene is composed of 18 exons and there are six splicing variants, but only four of them code for proteins. The secreted isoform found in the CM of breast cancer cell lines is the full-length isoform that consists of 898 aminoacids and has a molecular weight of 104 kDa. In the literature and in our data, it was shown that co-culture of breast cancer cells with fibroblasts results to an induction of HAS2 in fibroblasts and an increase of the secreted HA. Among the three HASes, HAS2 isoform was the most expressed and induced by breast tumour cells CM in fibroblasts, whereas HAS1 was not detected. When fibroblasts were treated with CM from MCF-7 cells, in the absence of Q7, the relative expression of HAS2 was significantly decreased. This last data was further confirmed when fibroblasts were treated with a recombinant protein of Q7 and a HAS2 induction and HA increase were observed. To sum up, the data of this thesis demonstrate that the novel protein Q7 may play a key role in the increment of pericellular HA and in the breast tumour progression

Negative priming 1985 to 2015 : A measure of inhibition, the emergence of alternative accounts, and the multiple process challenge.

In this article, three generations of authors describe the background to the original article; the subsequent emergence of vigorous debates concerning what negative priming actually reflects, where radically different accounts based on memory retrieval were proposed; and a re-casting of the conceptual issues underlying studies of negative priming. What started as a simple observation (slowed reaction times) and mechanism (distractor inhibition) appears now to be best explained by a multiple mechanism account involving both episodic binding and retrieval processes as well as an inhibitory process. Emerging evidence from converging techniques such as functional magnetic resonance imaging (fMRI), and especially electroencephalography (EEG), is beginning to identify these different processes. The past 30 years of negative priming experiments has revealed the dynamic and complex cognitive processes that mediate what appear to be apparently simple behavioural effects. </jats:p

Francesca Romana Nocchi, Commento agli Epigrammata Bobiensia, Series: Texte und Kommentare 54, Berlin-Boston: De Gruyter, 2016, x+482 pp., ISBN 978-3-11-046201-2.

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L'italiano dello sport: prospettive glottodidattiche e pratiche interculturali

Teaching a language is not only about vocabulary, grammar or pronunciation – it is also a very important form of cultural mediation. How can sport contribute to the intercultural dimension of language learning? The present work focuses on this question, with particular regard to Italian as a foreign language. The research faces two main perspectives: the textual dimension (Cap. 2), whereby that sectorial languages and text production in many different fields - newspaper, cinema, music, advertising, comics as well as literature- are considered, and the didactic dimension (Cap. 3), focused on the analysis of pre-existing teaching material, evaluated through the most relevant didactic methods. Actually, even if sport appears as a topic in several textbooks, itsdiversity on a linguistic and cultural level has not been sufficiently considered yet. Yet, sport has increasingly taken on a crucial role in our society as a vehicle of universal values; in such a way, sport is no longer only a private activity but a very important cultural and social practice. As a consequence, sport can set the basis for the development of intercultural communicative competence; to this end, the present work proposes a didactic approach which is attentive not only to linguistic implications, but also to cultural aspects. Last but not least, the ultimate relevance and urgency of this topic regards the extreme and irrefutable socio-political relevance of sport in general, and consequently the knowledge of the language of sport, in our multicultural and globalized world, where sport can provide an invaluable contribution to social integration and inclusion