1,720,967 research outputs found
Amyloid formation by mutant huntingtin: threshold, progressivity and recruitment of normal polyglutamine proteins
No full textHuntington's disease (HD) is caused by an expanded CAG trinucleotide repeat
encoding a tract of consecutive glutamines near the amino terminus of huntingtin,
a large protein of unknown function. It has been proposed that the expanded
polyglutamine stretch confers a new property on huntingtin and thereby causes
cell and region-specific neurodegeneration. Genotype-phenotype correlations
predict that this novel property appears above a threshold length (approximately
38 glutamines), becomes progressively more evident with increasing polyglutamine
length, is completely dominant over normal huntingtin and is not appreciably
worsened by a double genetic dose in HD homozygotes. Recently, an amino terminal
fragment of mutant huntingtin has been found to form self-initiated fibrillar
aggregates in vitro. We have tested the capacity for aggregation to assess
whether this property matches the criteria expected for a fundamental role in HD
pathogenesis. We find that that in vitro aggregation displays a threshold and
progressivity for polyglutamine length remarkably similar to the HD disease
process. Moreover, the mutant huntingtin amino terminus is capable of recruiting
into aggregates normal glutamine tract proteins, such as the amino terminal
segments of both normal huntingtin and of TATA-binding protein (TBP). Our
examination of in vivo aggregates from HD post-mortem brains indicates that they
contain an amino terminal segment of huntingtin of between 179 and 595 residues.
They also contain non-huntingtin protein, as evidenced by immunostaining for TBP.
Interestingly, like the in vitro aggregates, aggregates from HD brain display
Congo red staining with green birefringence characteristic of amyloid. Our data
support the view that the expanded polyglutamine segment confers on huntingtin a
new property that plays a determining role in HD pathogenesis and could be a
target for treatment. Moreover, the new property might have its toxic
consequences by interaction with one or more normal polyglutamine-containing
proteins essential for the survival of target neurons
Differential expression of normal and mutant Huntington’s disease gene alleles
No full textHuntingtin expression was examined by Western blot and immunoprecipitation
studies of lymphoblastoid cell lines from Huntington's disease (HD) homozygotes,
heterozygotes, and a phenotypically normal individual with a t(4p16.3;12p13.3)
breakpoint in the HD gene. The latter produced a reduced level of normal
huntingtin without evidence of an altered protein, indicating that simple loss of
huntingtin activity does not cause HD. In juvenile onset HD heterozygotes, NH2-
and COOH-terminal antisera revealed reduced relative expression from the mutant
allele. Pulse-chase studies indicated that huntingtin is a stable protein whose
differential allelic expression is not due to destabilization of the mutant
isoform. No stable breakdown products specific to mutant huntingtin were detected
in either HD homozygotes or heterozygotes. These data are consistent with HD
involving either a gain of function or a dominant negative loss of function that
operates within severe constraints and suggest that in either case the pathogenic
process is usually saturated by the amount of abnormal huntingtin produced from a
single mutant allele
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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