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Specific serological profiles in patients with inflammatory myopathies
No full textIl progetto di ricerca svolto durante il dottorato ha previsto lo studio di alcune forme di miopatia infiammatoria idiopatiche. Queste costituiscono un gruppo eterogeneo di malattie muscolari distinguibili tra loro clinicamente, istologicamente e patogeneticamente, ma che condividono la presenza di infiltrati infiammatori a livello muscolare. Sono classificate in tre gruppi: polimiosite, dermatomiosite e miosite a corpi inclusi. L’eziologia autoimmune per le forme di dermatomiosite e polimiosite e’ comprovata da alcune osservazioni (la presenza di autoanticorpi circolanti, l’associazione con altre patologie autoimmuni e la responsivita’ alle terapie con steroidi). E’ nota anche l’associazione di polimiosite e dermatomiosite con alcune forme neoplastiche. Solitamente la diagnosi di neoplasia precede o segue di 3/5anni la comparsa della miopatia. L’ipotesi patogenetica per le forme paraneoplastiche e’ che gli antigeni del tumore causano la produzione di autoanticorpi che cross-reagiscono con componenti del muscolo scheletrico.
Ad oggi non sono ancora noti gli antigeni muscolo-specifici responsabili della miopatia, ne’ nelle forme idiopatiche, ne’nelle forme paraneoplastiche. Lo scopo di questo studio e’ stato quello di individuare gli auto-antigeni muscolo-specifici riconosciuti dagli anticorpi circolanti dei pazienti. Sono stati analizzati 150 sieri provenienti da controlli e pazienti. L’impiego delle moderne tecniche di 2D-PAGE e di immunomica associate alla massa, ha permesso di individuare una serie di antigeni miosite-specifici e miosite-associate, nonche’ alcuni markers paraneoplstici specifici per le forme associate ai tumori della mammella, del polmone e dell’ovaio.
Le stesse tecniche sono state impiegate anche per lo studio di altre patologie muscolari.
In particolare sono state individuate alcune proteine muscolari riconosciute in maniera specifica dal siero di alcuni pazienti affetti da miopatia necrotizzante. Abbiamo notato l’attivazione del sistema del complemento e la deposizione di IgG sulla membrana plasmatica di fibre muscolari non necrotiche. Dall’analisi proteomica abbiamo individuato auto-anticorpi circolanti presenti in maniera specifica nei sieri dei pazienti affetti da miopatia necrotizzante e non nei casi controllo.
Abbiamo poi applicato questa metodica di proteomica per lo studio di alcune forme di miopatia miofibrillare. Questa patologia e’ caratterizzata dalla presenza di accumuli di proteine (desmina, miotilina, alfa-B cristallina e altre) all’interno delle fibre muscolari. L’analisi genetica delle proteine presenti negli accumuli ha evidenziato la presenza di mutazioni. La presenza di mutazioni, pero’, e’ stata individuata in una piccola percentuale di pazienti. L’eziologia di questa patologia e’ sconosciuta. Nello studio, abbiamo individuato la compresenza di una risposta infiammatoria a livello muscolare e la presenza di accumuli intracellulari tipiche delle miopatie miofibrillari in due pazienti. In questi pazienti sono state escluse mutazioni nei geni solitamente coinvolti in questa patologie. Dallo studio di proteomica e immunomica, abbiamo individuato alcune proteine riconosciute in maniera specifica dai sieri di questi pazienti e non dai casi controllo. Abbiamo quindi individuato per la prima volta un sottogruppo di miopatie mio fibrillari immuno-mediate.The research project carried out during the PhD was about the idiopathic inflammatory myopathies. They are classified into three groups: polymyositis, dermatomyositis and inclusion body myositis These acquired diseases have in common the presence of moderate to severe muscle weakness and endomysial inflammation, but each subset retains characteristic clinical, immunopathological, and morphological features. The autoimmune etiology for dermatomyositis and polymyositis is supported by some observations (the presence of circulating autoantibodies, the association with other autoimmune diseases and responsiveness to steroid treatment). The association between malignancy and autoimmune myositis has been largely described and confirmed by numerous epidemiological studies
The diagnosis of the malignancy may occur before, concurrently to, or following the diagnosis of myositis but despite this potentially confusing observation, what is quite useful is the knowledge that cancer is usually recognized within 3-5 years of myositis diagnosis, with most diagnoses within 12 months. Is not completely understood if antigens are shared between muscle and tumor cells or if there is a cross-reactivity between some epitopes expressed in both cell types
Despite the presence of a humorally-mediated inflammatory response targeting muscle fibers in DM, PM and OS, specific muscle antigens are not yet identified. In the study we characterized the muscle-specific proteins recognized by sera of patients with DM and PM and OS using a 2-DE approach. We also evaluated the sera of patients with myositis and cancer to validate the hypothesis of causal link between the diseases
The same techniques were used for the study of other muscle diseases.
We identified some muscle proteins specifically recognized by serum of some patients with immune mediated necrotizing myopathy. We found the activation of the complement system and deposition of IgG on the plasma membrane of non necrotic fibers. With proteomic analysis we identified circulating autoantibodies specifically present in the sera of patients with necrotizing myopathy and not in control cases.
We then applied this method in proteomics for the study of certain forms of myofibrillar myopathy. This pathologies is characterized by accumulation of proteins (desmin, myotilin, alpha-B crystalline and others) within the muscle fibers. Genetic analysis of proteins present in the deposits showed the presence of mutations. The presence of mutations, however, 'and' have been identified in a small percentage of patients. The etiology of this disease is still unknown. In the study, we identified the presence of inflammatory responses in the muscle and the presence of intracellular accumulation typical of myofibrillar myopathy in two patients. In these patients were excluded mutations in the genes usually involved in this disease. With proteomic study we have identified proteins specifically recognized by sera from these patients and not by control cases. We then identified for the first time a subset of immune-mediated myofibrillar myopathy
Sul banale
No full textLa ricerca prende le mosse dal dialogo tra architettura e psicoanalisi e attraversa una delle possibili traduzioni spaziali della nozione di “desiderio” mettendo a fuoco i significati del termine “banale”. A partire dall’etimo della parola, che rimanda al “bando di legge”, l’indagine si muove nel conflitto tra desideri individuali e il rassicurante “così fan tutti”, quindi tra norma e forma, per cercare nelle insidie della banalità i modi per accettarla o trasfigurarla. Il piano teorico e quello fisico si incrociano negli strumenti della ricerca sul banale, per verificare le strutture spaziali sottese attraverso diagrammi concettuali e per lasciar emergere la sua natura perturbante materializzandola sotto forma di modello
A metabolic shift induced by a PPAR panagonist markedly reduces the effects of pathogenic mitochondrial tRNA mutations.
No full textMutations in mitochondrial DNA-encoded tRNA genes are associated with many human diseases. Activation of peroxisome proliferator-activated receptors (PPARs) by synthetic agonists stimulates oxidative metabolism, induces an increase in mitochondrial mass and partially compensates for OXPHOS defects caused by single OXPHOS enzyme deficiencies in vitro and in vivo. Here, we analyzed whether treatment with the PPAR panagonist bezafibrate in cybrids homoplasmic for different tRNA mutations could ameliorate the OXPHOS defect. We found that bezafibrate treatment increased mitochondrial mass, mitochondrial tRNA steady state levels and enhanced mitochondrial protein synthesis. This improvement resulted in increased OXPHOS activity and finally in enhanced mitochondrial ATP generating capacity. PPAR panagonists are known to increase the expression of PGC-1α, a master regulator of mitochondrial biogenesis. Accordingly, we found that clones of a line harboring a mutated mitochondrial tRNA gene mutation selected for the ability to grow in a medium selective for OXPHOS function had a 3-fold increase in PGC-1α expression, an increase that was similar to the one observed after bezafibrate treatment. These findings show that increasing mitochondrial mass and thereby boosting residual OXPHOS capacity can be beneficial to an important class of mitochondrial defects reinforcing the potential therapeutic use of approaches stimulating mitochondrial proliferation for mitochondrial disorders
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
Spazi del desiderio tra architettura e psicoanalisi
No full textQuesto libro prende le mosse da dialoghi sulle possibili interferenze tra architettura e psicoanalisi intorno al fuoco della nozione di “desiderio”. I diversi autori danno forma alle trame del desiderio nei reticoli della mente, alla trasposizione iconologica di un soggetto immateriale, al pensare architettura traducendo in spazio ciò che appare più intangibile.
Il paesaggio delle posizioni raccolte restituisce vie effettive e possibili del desiderio costringendolo nei binari della macchinazione dei campi del sapere dell’architettura e della psicoanalisi che molto hanno in comune. Seppur distanti per tecniche e metodologie, entrambe le discipline s’incontrano nello spazio nascosto del pensiero e in quello concreto della realtà.
Sono presenti contributi di Sara Marini, Matteo De Simone, Claudio Ubaldo Cortoni, Maria Federica Tartarelli, Sissi Cesira Roselli, Egidio Cutillo, Alberto Petracchin, Arianna Mondin, Andrea Pastorello, Federica Sveva Caregnat
Essays in Behavioural and Experimental Economics: Emotions, Uncertainty and Cooperation
Full text linkIn the first chapter of the dissertation I conduct a laboratory experiment in
order to study the effect of incidental sadness and happiness on risky decision
making. The analysis reveals that both sadness and happiness are conducive
to greater risk aversion with respect to neutral conditions, a result which is
consistent with the theory of ego depletion but might be moderated by the
risk elicitation task.
The second chapter is a meta-analysis of experimental studies on the
same topic, so as to explain traditional heterogeneity of outcomes in the field.
Among the findings, emotions induce higher risk aversion when a multiple
price list à la Holt and Laury (2002) is used in place of stated preferences
methods, as well as in case the risk elicitation task is framed as an investment
decision instead of an abstract choice. Accordingly, I recommend faithful
study replication as preferential path for future investigations.
The third chapter offers experimental evidence on the impact of communication on the provision of binary threshold public goods whose quality
is uncertain. I find that communication significantly increases public good
provision by reducing undercontribution, although massive overcontribution
is observed. Therefore, I propose the pursuit of symmetric payoffs within the
group as effective explanation and I nally speculate that under uncertainty
satisficing is more salient than optimizing.En el primer capítulo de la tesis se realiza un experimento de laboratorio con
el fin de estudiar el efecto de las emociones de tristeza y felicidad, sentidas
como casuales no relacionadas con la decisión propiamente dicha, sobre la
toma de decisiones bajo riesgo. El análisis revela que los dos tipos de emociones, tanto tristeza como felicidad, suponen mayor aversión al riesgo en
relación a condiciones neutrales, un resultado que puede moderarse por la
tarea de elicitación de actitud frente al riesgo.
El segundo capítulo es un metanálisis de estudios experimentales sobre el
tema analizado en el primer capítulo, con el objetivo de explicar la heterogenidad tradicional de los resultados en la literatura sobre el tema. Como
resultado, las emociones inducen mayor nivel de aversión al riesgo cuando la
elicitación se realiza a partir de una lista múltiple de precios à la Holt and
Laury (2002) en vez de con métodos de preferencias declaradas. También
ocurre cuando la tarea de elicitación de la actitud frente al riesgo se etiqueta
como una decisión de inversión en vez de una elección abstracta.
El tercer capítulo ofrece evidencia sobre el impacto de la comunicación en
la provisión de bienes públicos cuya calidad es incierta. Se encuentra que la
comunicación incrementa de forma significativa la provisión del bien público
reduciendo la ineficiencia que proviene de una contribución derrochadora e
ineficiente, sin embargo se observa una masiva sobre-contribución. Por lo
tanto, se propone la búsqueda de pagos simétricos dentro del grupo como
explicación persuasiva y se especula en definitiva que, en condiciones de incertidumbre, se prioriza satisfacer a optimizar.Programa de Doctorat en Economia i Empres
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