1,720,971 research outputs found
Analisi genetica della malattie complesse: loci comuni e loci specifici
Full text linkIl completamento del progetto genoma umano ha dato nuovi impulsi allo studio della variabilità umana, dimostrando che ogni individuo differisce da qualsiasi altro solamente per lo 0.5% della propria sequenza di DNA. Responsabili di questa porzione variabile di genoma sono in particolare i polimorfismi a singolo nucleotide (SNPs - Single Nucleotide Polymorphisms), specifiche basi del DNA che variano negli individui con una frequenza maggiore di quella riscontrata per le mutazioni puntiformi.
Lo studio della variabilità interindividuale rappresenta una sfida per la medicina moderna soprattutto nella prospettiva di poter curare il malato in maniera sempre più specifica e sicura, individuando il trattamento terapeutico più efficace.
In particolare lo studio delle varianti polimorfiche è diventato determinante nella comprensione dei meccanismi alla base della suscettibilità alle diverse patologie multifattoriali, tra cui rientrano malattie comuni quali l’asma, la psoriasi, il diabete, l’obesità, e le malattie cardiovascolari.
I risultati degli studi familiari, degli studi sui gemelli e di quelli di adozione, hanno dimostrato che i fattori genetici rivestono un ruolo fondamentale nella patogenesi di molti difetti congeniti (cardiopatie, labiopalatoschisi, lussazione congenita dell’anca, etc.) e di molte comuni malattie croniche dell’adulto (ipertensione, diabete, malattie cardiovascolari, psoriasi, asma, etc.).
Sono patologie che si presentano con frequenze elevate nella popolazione, con un forte impatto sociale e dal peso rilevante sulla struttura sanitaria, tra le cause principali di morbilità e mortalità nei paesi occidentali.
La complessità è una condizione “normale” in biomedicina. Si chiamano infatti “complesse” le malattie umane più comuni. La crescente capacità di identificare le variazioni genetiche associate con le malattie complesse sta creando nuove sfide alla comunità dei ricercatori e dei clinici.
L’identificazione delle varianti di suscettibilità alle patologie comuni promette, di avere notevoli ripercussioni in ambito medico (miglioramento della terapia, valutazione della risposta individuale ai farmaci, comprensione della risposta adattativa degli organismi agli stimoli ambientali) ed in ambito economico e sociale (diminuzione dei costi elevati a carico del sistema sanitario).
La ricerca delle basi genetiche delle malattie complesse è progredita contestualmente all’evoluzione della biologia molecolare. Pertanto si è passati dallo studio del singolo locus di suscettibilità, identificato mediante analisi di linkage agli studi completi del genoma che consentono di analizzare molti più loci contemporaneamente.
Questo progetto di Dottorato è stato incentrato sulla ricerca di regioni genomiche, geni e varianti geniche correlate alla suscettibilità per specifiche malattie dermatologiche di natura infiammatoria e/o immunomediata, quali psoriasi, dermatite atopica.
Entrambe malattie dermatologiche rappresentano degli ottimi modelli sperimentali per lo studio delle patologie multifattoriali, in quanto estremamente frequenti ed eterogenee sia a livello fenotipico che genetico.
La pelle è un organo di difesa ed è spesso soggetta a stress fisici e meccanici. In queste condizioni patologiche lo strato corneo, con il suo ruolo protettivo va incontro a modificazioni chimiche che ne limitano la funzione di barriera.
L’attività di ricerca è stata rivolta innanzitutto all’analisi di una stessa regione genomica, correlata alla suscettibilità per patologie dermatologiche diverse, che potrebbe essere coinvolta proprio nella natura infiammatoria delle patologie in esame ed, in secondo luogo, all’analisi di regioni specifiche, al fine di comprendere meglio, tramite analisi molecolari peculiari, la patogenesi delle patologie analizzate.
La natura mutualmente esclusiva della psoriasi e della dermatite atopica, patologie che raramente sono osservate contemporaneamente nello stesso paziente, suggerisce che probabilmente diversi possono essere gli alleli di suscettibilità causativi o regolatori. Nonostante ciò le due malattie sono associate alle medesime regioni cromosomiche e presentano caratteristiche cliniche comuni quali la secchezza cutanea, problemi di permeabilità della barriera epidermica e difetti nella funzione di difesa svolta dall’epidermide.
In particolare in questo studio è stata condotta un’analisi accurata del locus PSORS4/ATOD2, che mappa sul braccio lungo del cromosoma 1 (1q21), isolato nella popolazione italiana e responsabile della suscettibilità sia alla psoriasi che alla dermatite atopica
The psoriasis genetics as a model of complex disease
No full textPsoriasis [OMIM*177900] is a common, chronic and papulosquamous inflammatory skin disease affecting approximately 2% of Caucasian. However, this disorder is rare among Japanese, Eskimos, West Africans and North American blacks and very uncommon in North American and South American natives. The causes for these variations are likely to be both genetic and environmental. Population-based studies and twin studies indicate that psoriasis is a heritable disease with a polygenic mode of inheritance with variable penetrance. Independent genome-wide scans have suggested the involvement of a large number of chromosomal regions (loci), and many candidate genes have been proposed. We discuss genetic approaches to the disease, results and interpretations of relevant studies, as well as future perspectives. Understanding the genetic basis of psoriasis will represent a major advance in our understanding of the disease and will reveal novel disease-specific biologic pathways
Mapping the future of common diseases: lessons from psoriasis
No full textPsoriasis (OMIM*177900) is a common, chronic, hyperproliferative inflammatory disorder of the skin affecting approximately 2% of Caucasians. Despite the prevalence of psoriasis in general population, significant differences in the incidence among Japanese, Eskimos, West Africans, north American blacks and American natives are well known. The cause for these variations are likely to be both genetic and environmental. Independent genomewide scans have suggested the involvement of a large number of chromosomal regions (loci), but so far only poor susceptibility genes have been suggested. We discuss genetic basis of the disease, results and interpretations of relevant studies, with particular regard to study design and future perspectives. Indeed to date, mapping genes which contribute to complex diseases is one of the major challenge in the post-genomic era
Demolition and construction recycling unified management: the DECORUM platform for improvement of resource efficiency in the construction sector
No full textThe construction and public work sectors are faced with a series of challenges that will need to be addressed in moving towards an effective circular economy model. The aim of this work was to develop a simple but holistic approach to the management of construction projects in order to ensure compliance with technical standards and environmental criteria right from the set-up phase and to foster an increased use of recycled materials and saving of natural resources. To achieve this goal, a multi-user platform was designed and developed to manage and control all stages and procedures of public work and provide support to all those involved throughout the various stages of implementation. The platform included (1) technical standards; (2) environmental law; (3) databases; (4) technical specifications for public tenders; (5) a tool to assess environmental impacts and circularity; (6) a marketplace to facilitate and transparently manage trading of natural, artificial, and recycled aggregates; (7) interactive catalogues with declarations of building products; and (8) interactive maps for the geolocation of treatment plants, producers, and construction sites. The platform, currently undergoing validation by public administrations, will represent a valuable tool for use in enabling public work contractors to reduce environmental impacts, promote an informed and transparent use of recycled products, and to encourage a more sustainable use of natural resources. The platform will facilitate the application of green public procurement (GPP) which, although mandatory in several countries (e.g., in Italy), continues to encounter a series of problems in implementation. The platform will also enhance compliance with technical standards and minimum environmental criteria (MEC), as recently defined for buildings and road construction and maintenance, thus expanding the market for artificial and recycled aggregates with certified products and guaranteed quality
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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