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Analisi genetica e meccanismi molecolari alla base di patologie rare dell'epidermide
Get PDFLe genodermatosi o "disordini della cheratinizzazione", sono così definite perche' hanno come base dei difetti genetici, che hanno come conseguenze caratteristiche cliniche ed istopatologiche molto variabili e spesso sovrapponibili. Per questi motivi e a causa della loro rarità, la loro classificazione è molto complessa. In alcune patologie dermatologiche il meccanismo molecolare alla base della malattia può essere identificato nell'alterazione di un singolo gene, mentre in altri casi sono coinvolti numerosi fattori. In generale, si tratta di malattie deturpanti ma raramente letali che si presentano con gradi di severità variabile. I cambiamenti morfologici dei cheratinociti, durante il loro differenziamento, sono determinati da modificazioni biochimiche che riflettono un programma d’attivazione ed inibizione sequenziale a carico di vari prodotti genici specifici per il differenziamento. Qualsiasi difetto nei suoi componenti strutturali, sia proteici che lipidici, o negli enzimi responsabili della loro sintesi, del loro processamento e assemblaggio, possono distruggere la barriera epidermica o alterarne il processo di turnover dando luogo ad una varietà di stati morbosi. Lo studio dei diversi fattori che intervengono nello sviluppo epidermico è necessario ai fini di una maggiore comprensione delle cause dell’insorgere delle genodermatosi. In questa tesi sono state affrontate tre diverse patologie epidermiche, associate a tre diversi geni, che possiedono però alcune caratteristiche fenotipiche comuni.
Sono stati analizzati 60 pazienti italiani diagnosticati per l’ittiosi lamellare, un disturbo congenito della cheratinizzazione che si trasmette in maniera autosomica dominante, al fine di avere un quadro più ampio sulle mutazioni ricorrenti nella nostra popolazione. Abbiamo utilizzato un approccio specifico per l’analisi molecolare del gene TGM1, che codifica per la transglutaminasi 1 (TGasi1), noto per essere uno dei geni responsabili dell’insorgere della patologia. La metodica messa a punto in questo lavoro può essere considerata un approccio alla diagnosi prenatale specifica per l’ittiosi lamellare TGasi1 dipendente.
È stato inoltre affrontato lo studio di una diversa forma di ittiosi, la sindrome di Sjogren-Larsson (SLS) causata da mutazioni del gene ALDH3A2 che codifica per l’enzima FALDH, fondamentale per il metabolismo degli acidi grassi. L’obiettivo di questo studio è stato il chiarimento delle dinamiche molecolari responsabili dell’insorgere di questa patologia nella popolazione italiana al fine di utilizzare le nostre conoscenze per una diagnosi più completa ed efficace. In questo lavoro presentiamo due casi distinti di cui uno causato dalla presenza di una mutazione fino ad oggi non ancora descritta in letteratura.
La terza patologia oggetto di questo lavoro di tesi, presenta un fenotipo ittiosico ed altre caratteristiche fenotipiche legate al differenziamento epidermico. La KID sindrome (Keratitis-Ichtyosis-Deafness) è causata da mutazioni del gene GJB2 che codifica per la connessina 26, una proteina necessaria per l’assemblaggio delle giunzioni comunicanti (gap junction). Nei due pazienti analizzati in questo studio sono state riscontrate due diverse mutazioni, di cui una mai descritta in letteratura, e sono state caratterizzate le due proteine mutanti al fine di evidenziare eventuali differenze funzionali, responsabili dei meccanismi che provocano l’insorgere di questa patologia. Utilizzando diversi approcci, uno citofluorimetrico, l’altro elettrofisiologico, abbiamo potuto inoltre evidenziare il coinvolgimento delle due proteine mutanti nella regolazione del flusso di calcio intracellulare e nel loro coinvolgimento nell’induzione di morte cellulare attraverso meccanismi di necrosi.The disorders of keratinisation are also defined “genodermatosis” because of their genetic basis, and they are characterized by very different, and often overlapping, clinical and histopathological features that affect skin. For these reasons and because of their rarity, their classification is very complex. For some of these diseases, the molecular mechanism can be identified as mutations of a single gene, but for others it involves several factors. Generally these disfiguring diseases are rarely fatal, and have different degrees of severity. The morphological changes of keratinocytes occurred during their differentiation are determined by biochemical changes as result of programmed activation and inhibition of several specific differentiation proteins. Any skin defects in its structural components (fat proteins or enzymes responsible for their synthesis), in its processing or assembly, can destroy the skin barrier or alter turnover process, resulting in a variety of pathological conditions. The study of factors involved in developing skin is indispensable for a deeper understanding of genodermatosis onset. The object of this work consists of three different skin diseases, associated with three different genes but with some common phenotypic characteristics.
We analyzed 60 Italians patients affected by lamellar ichthyosis, a congenital autosomal dominant disorder of keratinization, in order to analyze and summarize common mutation in our country. We used a specific approach for the molecular analysis of TGM1 gene, which encodes the transglutaminase 1 (TGasi1), known as one of the responsible genes for disease onset. The method which we developed in this work can be considered an approach for prenatal diagnosis of specific TGasi1-dependent lamellar ichthyosis.
We also analyzed Sjogren-Larsson syndrome (SLS), another form of ichthyosis caused by ALDH3A2 mutations, which codes for the FALDH enzyme, a crucial protein for the fatty acids metabolism. This study aims to clarify the molecular mechanism responsible for the onset of this disease in Italy, in order to use our knowledge for a more complete and effective diagnosis. In this work we show two separate cases, one caused by a new mutation not yet described in literature.
The third pathology analyzed in this work has an ichthyotic phenotype and other phenotypic characteristics associated with epidermal differentiation. This disease, named KID syndrome (Keratitis-Ichtyosis-Deafness), is caused by mutations in the GJB2 gene, coding for the connexin 26. This protein is necessary for gap junction assembly. In this study were found two different mutations in two patients, one of these never described in literature. We analyzed the mutant proteins arising from these two mutations in order to highlight possible differences in the functional mechanisms causing the onset of the disease. Using cytofluorometric and electrophysiological approaches, we could also clarify the involvement of the mutant proteins in intracellular calcium flow regulation and their involvement in the induction of cell death through necrosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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