1,720,988 research outputs found
Structural and functional insights into the biological function of mouse proNGF
Full text linkIn the recent years one of the lines of in
vestigation in the Neur
obiology Laboratory
at SISSA has been to study the molecular det
erminants of Alzheimer’s Disease (AD),
one of the most known and diffused neur
odegenerative aging diseases. AD is
characterized by lesions in the brai
n cortex, including the presence of
β
-amyloid
plaques and neurofibrillary tangles c
ontaining phosphorylated tau protein.
In Alzheimer’s disease neuronal degeneration
is found in selected areas of the
brain, in particular in cortical, hippocam
pal and basal forebrain cholinergic neurons
(reviewed in Price
et al
., Ann. Rev. Neurosci., 1986)
. The investigation on the
involvement of the neurotrophin Nerve Gr
owth Factor (NGF) in AD has been
extensive, because it promotes
the survival and regulates
the function of cholinergic
neurons of the basal forebr
ain. (reviewed in Counts
et al.
, J. Neuropath. Exp. Neuro.,
2005).
NGF is translated as a pre-
pro-protein, proNGF, the im
portance of which in the
recent years has grown much, thanks to impor
tant findings on its bi
ological functions,
besides the one of promoting protein foldin
g. Accordingly, the
increasing number of
involved new actors has complicated also t
he scenario of the investigations on the
molecular determinants in AD
COMPOSIZIONI IN GRADO DI PREVENIRE EVENTI NEURODEGENERATIVI E METODO PER SAGGIARNE L'ATTIVITA'
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NGF and proNGF Reciprocal Interference in Immunoassays: Open Questions, Criticalities, and Ways Forward
Full text linkThe homeostasis between mature neurotrophin NGF and its precursor proNGF is thought to be crucial in physiology and in pathological states. Therefore, the measurement of the relative amounts of NGF and proNGF could serve as a footprint for the identification of disease states, for diagnostic purposes. Since NGF is part of proNGF, their selective identification with anti-NGF antibodies is not straightforward. Currently, many immunoassays for NGF measurement are available, while the proNGF assays are few and not validated by published information. The question arises, as to whether the commercially available assays are able to distinguish between the two forms. Also, since in biological samples the two forms coexist, are the measurements of one species affected by the presence of the other? We describe experiments addressing these questions. For the first time, NGF and proNGF were measured together and tested in different immunoassays. Unexpectedly, NGF and proNGF were found to reciprocally interfere with the experimental outcome. The interference also calls into question the widely used NGF ELISA methods, applied to biological samples where NGF and proNGF coexist. Therefore, an immunoassay, able to distinguish between the two forms is needed. We propose possible ways forward, toward the development of a selective assay. In particular, the use of the well validated anti-NGF αD11 antibody in an alphaLISA assay with optimized incubation times would be a solution to avoid the interference in the measurement of a mixed sample containing NGF and proNGF. Furthermore, we explored the possibility of measuring proNGF in a biological sample. But the available commercial kit for the detection of proNGF does not allow the measurement of proNGF in mouse brain tissues. Therefore, we validated an SPR approach for the measurement of proNGF in a biological sample. Our experiments help in understanding the technical limits in the measurement of the NGF/proNGF ratio in biological samples, and propose concrete solutions toward the solution of this problem
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
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