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    Adipocita e Flogosi: Ruolo di Adipochine e Vitamina D

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    L’obesità è una condizione caratterizzata da infiammazione cronica del tessuto adiposo (TA), che si associa ad aumentato rischio non solo metabolico ma anche neoplastico, con prognosi peggiorative. È stato ipotizzato un ruolo del TA nel crosstalk con le cellule del sistema immunitario e quindi della patogenesi dello stato infiammatorio subclinico correlato all’obesità. In questa tesi si è voluto indagare la modulazione della flogosi in diverse condizioni sperimentali. Nel modello sperimentale di cellule murine 3T3-L1, stimolate con lipopolisaccaride (LPS) a diversi dosaggi e tempi, sono state indagate le espressioni di diverse adipochine, sia come mRNA da lisato cellulare, che come proteine secrete nel surnatante, osservando un aumento di espressione di citochine infiammatorie (IL-6, TNF-α, CCL3, CCL4, CXCL12) e riduzione di proteina antinfiammatoria (IL-10). È stato quindi valutato il ruolo del calcitriolo (1,25[OH]2D3) nella fisiologia e patofisiologia dell’adipocita, ed in particolare nella modulazione della flogosi del TA stesso. Si sono perciò indagati gli effetti trascrizionali e morfologici sia di 1,25[OH]2D3 che del precursore colecalciferolo (D3) su adipociti 3T3-L1, SGBS, ottenuti da colture primarie o isolati a fresco, in relazione alle stimolazioni con LPS in diverse [Ca2+]e. L’adipocita presentava enzimi atti al metabolismo della vitamina D3, CYP27A1 e CYP27B1. La stimolazione con D3 ha mostrato andamento simile a quella con 1,25[OH]2D3, ossia antinfiammatorio, con riduzione di IL-6, TNF-α ed aumento di IL-10. D3 e 1,25[OH]2D3 infatti, erano in grado di aumentare area e diametro degli adipociti con riduzione di densità ottica (optical density = OD), effetti opposti al trattamento con LPS. Tali azioni di D3 e 1,25[OH]2D3 nell’adipocita sembrano accentuati in presenza di aumentate [Ca2+]e. Sono state quindi analizzate le caratteristiche infiammatorie del TA peritumorale (PAT), in pazienti affetti da cancro al colon retto (CCR). Utilizzando campioni bioptici di TA è stato studiato il livello di infiammazione e infiltrazione macrofagica in PAT, TA viscerale (VAT) e sottocutaneo (SAT). Le indagini istopatologiche hanno evidenziato che gli adipociti del PAT abbiano dimensioni più ridotte rispetto a quelli di VAT e SAT. Inoltre PAT ha rivelato una prevalente infiltrazione di macrofagi M2, mentre in VAT e SAT i macrofagi infiltrati mostrano caratteristiche M1. Il PAT presenta altresì una maggiore espressione di adiponectina, paragonata con SAT e VAT. In conclusione nella loro globalità, questi dati dimostrano come la flogosi nel TA sia finemente regolata. Il TA è in grado di rispondere a diversi stimoli pro- ed anti-infiammatori, modulandone l’azione. Pertanto, soprattutto nell’ambito di alcune patologie (quali in cancro e la sindrome metabolica), cruciale sembra la possibilità di poter interferire con tali processi, allo scopo di ridurre la flogosi del TA, coinvolta nella loro patogenesi. Futuri studi dovranno proseguire nell’identificazione dei potenziali target utili per la modulazione della flogosi del TA.Obesity is bound to a cronic, low-grade inflamed status of adipose tissue (AT), associated not only with a metabolic risk, but also neoplastic, leading to worse prognosis about a broad spectrum of pathologies. It was supposed a leading role for AT as regard crosstalk with immune cells and AT inflamed status. The aim of this study was to investigate the relationship between adipocytes and inflammation. From an experimental model based on 3T3-L1 cells, stimulated with lipopolysaccharide (LPS) in various times and doses, expressions of adipokines was examined, as regards both mRNA from cellular lysate, and secreted proteins in cellular medium (with ELISA). Modulations were observed with general augmented expressions of inflammatory citokines (IL-6, TNF-α, CCL3, CCL4, CXCL12), while there was a reduction in anti-inflammatory response (IL-10). The role of calcitriol (1,25[OH]2D3) was investigated in adipocyte’s physiology and pathophysiology, in relation to adipogenic and inflammatory functions. For this reasons, transcriptional and morphological effects were investigated, both of 1,25[OH]2D3 and of its parent compound colecalciferol (D3) on adipocytes differentiated from 3T3-L1, SGBS, primary cultures preadipocytes and fresh-isolated adipocytes. Also in conjunction with [Ca2+]e and LPS stimulations. Adipocytes showed enzymes for D3, such as CYP27A1 and CYP27B1. D3 treatment showed a similar antiinflammatory trend compared to 1,25[OH]2D3 one, with a reduction in IL-6, TNF-α and an increase in IL-10. As regards morphology, some changes were observed, about lipid droplets’ optical density (OD), area and diameter of adipocytes. D3 and 1,25[OH]2D3, indeed, increased adipocytes area and diameter, reducing OD. LPS showed opposite effects, while pretreatment with D3 and 1,25[OH]2D3 spared variations induced by LPS stimulation. These effects seem to be highlighted by the increase of [Ca2+]e, also in relation with LPS treatment. Using AT bioptic material, the differences in adipocytes’ morphology were studied, inflammatory status and macrophages’ infiltration among peritumoral AT (PAT), visceral AT distant from the tumor (VAT) and subcutaneous AT (SAT). Histopathological analyses revealed that PAT adipocytes were smaller then VAT and SAT adipocytes. Furthermore, the PAT was mainly infiltrated by M2-subtype macrophages, while the macrophages identified in other AT depots presented mainly M1-features. PAT also presented a higher expression of adiponectin, compared to SAT and VAT. In conclusion, these data showed the AT response capabilities to inflammation are strictly regulated. AT seems to be able to react both to inflammatory and anti-inflammatory stimulations. Therefore, AT alterations could involve pathological effects, alike cancer or metabolic syndrome. So, any possibility to interfere with these processes could be pivotal, reducing AT inflammation. Future studies may identify potential targets useful to modulate inflammation in AT

    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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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