1,721,091 research outputs found
MALATTIA DI ALZHEIMER E DEGENERAZIONE LOBARE FRONTOTEMPORALE: RICERCA DI MUTAZIONI AUTOSOMICHE DOMINANTI E ANALISI GENETICA E FUNZIONALE DI GENI CANDIDATI
Get PDFThis PhD study is intended to perform a genetic screening on a population of AD and FTLD patients in order to identify pathogenetic causal mutations (PSEN1, PSEN2 and APP for AD; MAPT, GRN and the GGGGCC repeat expansion one the C9orf72 gene for FTLD) and to investigate the role of several candidate genes (GRN,TMEM106b and OLR1) considered to be risk factors for the two disease.
Eighteen patients were carriers of pathogenetic causal mutations: 1 carrier of Ala260Val (g.49964C>T) situated in exon 8 of PSEN1,16 carriers of GRN gene mutations and 1 carrier of a new variant, Gly304Ser (g.123789G>A), located in exon 10 of MAPT gene. The presence of GGGGCC repeat expansion, positioned on the first intron of C9orf72 gene, was analyzed in a larger population (651 FTLD patients, 21 CBD and 31 PSP patients). Thirty nine patients with FTLD were carriers of pathogenetic repeat expansion, whereas none of CBD and PSP patients as well as 222 controls carried the mutation. Several associations studies were performed in the remaining sporadic population of AD and FTLD patients. Regarding the influence of GRN genetic variability on susceptibility to AD, two SNPs rs9897526G>A and rs5848 were investigated. A tendency to an increased frequency of rs5848T allele was found in AD patients as compared with controls, whereas for the rs9897526 SNP, in patients carrying the rs9897526A variant was observed a significant earlier age at disease onset compared with patients carrying the G allele. The case-control study carried out on a populations of FTLD patients was focused on four Tagging SNPs (rs2879096, rs3785817, rs4792938 and rs9897526) as well as on rs5848 SNP, localized in the 3’UTR of GRN gene. A statistically significant association of the rs4792938 CC genotype was observed in FTLD patients compared with healthy controls. Concerning the role of TMEM106b gene on susceptibility to AD, an association analysis was performed on three SNP, rs1020004 A/G, rs6966915 C/T and rs1990622 A/G, but no significant differences in allelic and genotype frequencies were found for all polymorphisms between AD patients and controls. The possible functional importance of genetic variability associated with this gene was tested by plasmatic ELISA detection of GRN on eighty AD patients. Stratifying the results according to rs1990622 SNP status, no significant differences in progranulin plasma levels were found in AD patients. Regarding OLR1, in particular it was analyzed the SNP rs1050283 T/C, located in 3’UTR of the gene. Logistic regression analysis, adjusted for gender and ApoE status, showed a statistically significant association of OLR1 rs1050283 under the assumption of a dominant and a genotypic model. Therefore this SNP could be considered a susceptibility factor for sporadic AD. Given that the SNP rs1050283 is also located in a predicted binding site of the miRNA has-miR369-3p, a preliminary expression analysis was performed on the two transcripts in the PBMC in order to clarify a possible functional role of individual genetic variability on the expression of OLR1 gene. Stratifying the results according to the presence of rs1050283C allele, a significant decrease of relative expression levels of OLR1 was observed in patients carrying at least one polymorphic C allele, despite the normal expression levels of has-miR369-3p. These data suggest that the presence of the polymorphic allele could influence the binding of has-miR369-3p to its 3’UTR consensus sequence, in which the SNP is located
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
Innate immune system and inflammation in Alzheimer's disease : from pathogenesis to treatment
No full textImmune activation and inflammation, likely triggered by amyloid-beta (Aβ) deposition, play a remarkable role in the pathogenesis of Alzheimer's disease (AD), which is the most frequent cause of dementia in the elderly. The principal cellular elements of the brain innate immune system likely to be involved in such processes are microglia. In an attempt to search for new disease-modifying drugs, the immune system has been addressed, with the aim of removing deposition of Aβ or tau by developing vaccines and humanized monoclonal antibodies. The aim of this review is to summarize the current evidence regarding the role played by microglia and inflammatory molecules in the pathogenesis of AD. In addition, we will discuss the main active and passive immunotherapeutic approaches
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
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