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    Characterization of the role of CCRL2 in lung and intestine immune surveillance

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    The C-C chemokine receptor-like 2 (CCRL2) belongs to the class-A GPCR receptor and is related to the atypical chemokine receptors (ACKRs) family. It regulates leukocyte migration by acting as a Chemerin-presenting molecule, as well as forming heterodimers with other chemokine receptors. CCRL2 is expressed by a large variety of leukocytes and barrier cells and controls the inflammatory response in different pathological settings. For instance, in lung cancer CCRL2 is required for NK cell recruitment and immune surveillance. This thesis explored the multifaceted role of CCRL2 in the immune regulation of the lung and intestine. Firstly, we investigated the correlation between CCRL2 variants and the severity of COVID-19. Five CCRL2 missense polymorphisms common among Europeans were selected and investigated in the meta-analysis of the COVID-19 host genetics initiative (COVID19 HGI) and in the Italian cohort referring to the Humanitas Clinical and Research Center (Rozzano, Milan). We have identified an association between the p.I243V variant and severe respiratory COVID-19 in Europeans. Functional assessments revealed that these variants do not affect CCRL2 membrane expression or Chemerin binding. Additionally, we identify CCRL2 eQTLs specific to neutrophils, linked to COVID-19 associated SNPs, suggesting a targeted influence on neutrophils. The study also delved into CCRL2 involvement in the regulation of intestinal inflammation and tumorigenesis. Genetic ablation of Ccrl2 in murine models of DSS-induced colitis and AOM/DSS-induced colon cancer revealed a more severe inflammatory phenotype, a finding corroborated in VillinCreHe-CCRL2f/f mice, emphasizing CCRL2 role in regulating the intestinal epithelium. Furthermore, we have observed an increased permeability in intestinal organoids from Ccrl2 KO mice, suggesting a role for this receptor in maintaining intestinal barrier integrity. The absence of Ccrl2 also modulated the expression and release of certain pro-inflammatory cytokines and chemokines by intestinal organoids treated with TNF-α and IFN-. In conclusion, this study highlighted the impact of CCRL2 in neutrophil-mediated responses and COVID-19 severity. CCRL2 also plays a role in the regulation of intestinal epithelium functions and permeability, especially during inflammatory responses. Collectively, these results contribute to a more comprehensive understanding of CCRL2 functions and its potential implications in the immune surveillance of the lung and intestine

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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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