1,721,011 research outputs found
NEW EVIDENCES OF TWO DIFFERENT KEY PATHOGENIC MECHANISMS IN HUNTINGTON'S DISEASE
Full text linkHuntington’s disease (HD) is an adult-onset neurodegenerative disorder characterized by several alterations in critical molecular and cellular pathways. Although genetic and experimental evidence has provided insights into HD pathogenesis, and many hypotheses concerning its underlying mechanisms have been proposed, a treatment that delays disease onset or slows its progression is still missing (Zuccato et al., 2010). During my PhD, my research activity was focused on the investigation of new aspects of two key pathogenic mechanisms of HD: i) the reduction of Brain-Derived Neurotrophic Factor (BDNF) and ii) the cholesterol dysfunction.
Reduced BDNF levels have been described in a number of patho-physiological conditions, most notably, in HD. Since BDNF is also produced in blood, we have undertaken the measurement of its peripheral levels in the attempt to identify a possible link with HD prognosis and/or its progression. In the first part of my PhD, I evaluated BDNF level in 398 blood samples including 138 controls, 56 preHD, and 204 HD subjects. I found that BDNF protein levels were not reliably different between groups, whether measured in plasma (52 controls, 26 preHD, 105 HD) or serum (39 controls, 5 preHD, 29 HD). The analysis of the literature highlighted that intra-group variability and methodological aspects affect this measurement, especially in serum. Moreover during my PhD, I set up a novel strategy for mRNA normalization in quantitative real-time PCR that is based on expressed Alu repeat amplification as a measure for the mRNA fraction. I demonstrated that expressed Alu repeat amplification is a fast, accurate normalization tool that can be successfully used for quantification of selected mRNA in the human transcriptome. This result is particularly important for clinical diagnosis and biomarker validation studies based on mRNA detection in human blood. Based on this new normalization method, I measured BDNF mRNA levels in blood samples from 47 controls, 25 preHD, and 70 HD subjects, and found no differences among the groups. These results indicated that levels of BDNF in human blood were not informative (mRNA levels or plasma protein level) nor reliable (serum protein levels) as HD biomarkers.
Brain cholesterol, which is synthesized locally, is a major component of myelin and cell membranes and participates in several neuronal activities, such as neurite outgrowth and synaptogenesis. In post-natal life, the cholesterol-dependent activities of neurons mainly rely on the transport of cholesterol from astrocytes on ApoE-containing lipoproteins. Mounting evidence indicates that reduced cholesterol biosynthesis occurs in the brain of several models of Huntington’s disease (HD) and is manifest in astrocytes (Valenza et al., J. Neurosci 2010). However, how mutation in huntingtin elicits changes in cholesterol biosynthesis pathway is still unknown. In the second part of my thesis, I explored the cross-talk between neurons and astrocytes to determine whether reduced cholesterol biosynthesis/secretion by HD astrocytes influences cholesterol-dependent properties in wt (and HD) neurons, such as neurite outgrowth and synaptic vesicles formation/maintenance. Primary neurons and astrocytes expressing normal and mutant huntingtin have been used in different experimental settings, in order to evaluate i) the influence of cell non-autonomous mechanisms involving defective cholesterol synthesis/secretion by astrocytes bearing mutant htt and how this dysfunction affects networks and cholesterol-dependent properties of neurons that undergo degeneration in HD; ii) exploring the underlying molecular mechanism of the cholesterol biosynthesis dysfunction in HD astrocytes to identify potential targets of intervention from therapeutic standpoints. I show that glial-derived medium from wt astrocytes (GCMwt) and cholesterol administration improve neurite outgrowth and synaptic properties in wt and HD neurons. The same parameters are not increased after administration of GCM from primary HD astrocytes (GCMHD) or GCMwt depleted of lipoproteins. These findings support the hypothesis that non-cell autonomous mechanisms related to cholesterol and involving astrocytes may contribute to HD pathogenesis. Strategies aimed at selectively modulating brain cholesterol metabolism might be of impact in HD
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
Visual reeducation after surgical removal of choroideal neovascular membrane in Age-related Macular Degeneration
No full textHuman adipose stem cells can differentiate in an osteoblastic-like phenotype on trabecular titanium scaffolds without osteogenic medium
No full textIntroduction Pluripotent human adipose tissue-derived stem cells
(hASCs) can differentiate into multiple mesenchymal cell lineages Previous studies demonstrated that the material, the geometry and the
porosity of scaffolds affect cell binding and migration depth of cellular
ingrowth, and that hASCs can differentiate in an osteoblasticlike
phenotype when seeded on trabecular titanium scaffolds with
osteogenic medium. Aim of this study was to demonstrate that trabecular
titanium scaffolds could induce osteogenic differentiation of
hASCs also without osteogenic medium.
Materials and methods hASCs were isolated from subcutaneous
adipose tissue, seeded on monolayer and on trabecular titanium
scaffolds (Ti6Al 4 V, LimaCorporate, Villanova di San Daniele del
Friuli, Italy; average porosity, 65%, average diameter of cell pores,
640 lm) and incubated at 37 C in 5% CO(2) with osteogenic and
proliferation medium in static conditions. Cells before seeding corresponded
to reference group. After seeding on scaffolds, hASCs
were cultured for 7 days in the presence of proliferation medium
before the osteogenic medium was added (Time 0). The osteogenic
differentiation was detected with real-time PCR to analyze the
expression of ALP and RUNX-2 genes, at time 0 and after 3, 7 and
21 days from differentiation. Alkaline phosphatase activity on cell
lysates was also measured after 7 days from differentiation.
Results Monolayer: both ALP and RUNX-2 gene expression and
alkaline phosphatase activity were higher in hASCs grown in presence
of osteogenic medium.
Trabecular titanium scaffolds: in hASCs grown in proliferation
medium, ALP gene expression was higher than reference group still at
time 0, and remained 2.5 fold higher at time 3 and 7. Similar results
were found with osteogenic medium. RUNX-2 gene expression was
higher in hASCs grown in osteogenic medium, and increased also in
the presence of proliferation medium respect to reference group. At
time 7, there were no difference in alkaline phosphatase activity of
hASCs grown with proliferation and osteogenic medium.
Conclusions hASCs on trabecular titanium expressed higher amount
of ALP and RUNX-2 gene expression in proliferation medium with
respect to cells on monolayer in the same condition. The expression
of osteogenic genes similar in cells grown on scaffold with both
medium, leads to the conclusion that trabecular titanium scaffold
seems to have not only osteoconductive but also osteoinductive
properties
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
- …
