1,720,984 research outputs found
Molecular basis of facioscapulohumeral muscular dystrophy
No full textFacioscapulohumeral muscular dystrophy (FSHD), the third most common myopathy, is an autosomal dominant disease with an insidious onset and progression. Almost all FSHD patients carry deletions of an integral number of tandem 3.3 kb repeats, termed D4Z4, located on chromosome 4q35. In FSHD patients a deletion of the integral number of D4Z4 repeats generates a fragment that is usually smaller than 35 kb (fewer than 11 repeats), whereas in normal controls the size usually ranges from 50 to 300 kb (between 11 and 150 units). D4Z4 is a repetitive element with heterochromatic features. Recently, 4q35 genes located upstream of D4Z4 have been found to be inappropriately overexpressed specifically in FSHD muscle. An element within D4Z4 has been shown to behave as a silencer that provides a binding site for a transcriptional repressing complex. These results suggest a model in which deletion of D4Z4 leads to the inappropriate transcriptional derepression of 4q35 genes, resulting in disease
When Enough is Enough: Genetic Diseases Associated with Transcriptional Derepression.
No full textFor many human genetic diseases, the underlying geneticdefect has been determined. Thus, although traditionally afield only for researchers in medicine or human genetics,human diseases are now opening up to molecular biologists,cell biologists and biochemists. Here we discuss four humangenetic disorders, Familial Alzheimer’s disease, Rett syndrome,Klippel—Trenaunay syndrome and Facioscapulohumeralmuscular dystrophy, and how investigations into these diseasesare providing important lessons about human biology
Transcriptional derepression as a cause of genetic diseases
No full textTranscription of DNA into mRNA is a highly regulated process directed by a complex molecular machine comprising more than 100 proteins. Regulation of transcription occurs by both positive (transcriptional activation) and negative (transcriptional repression) mechanisms. Recently, inappropriate transcriptional derepression has been found as the underlying basis of several human genetic diseases. The putative target genes, whose inappropriate expression is thought to cause disease, have remained elusive but are being searched for intensively
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
Inappropriate gene activation in FSHD: A repressor complex binds a chromosomal repeat deleted in dystrophic muscle
Full text linkFacioscapulohumeral muscular dystrophy (FSHD), a common myopathy, is an autosomal dominant disease of unknown molecular mechanism. Almost all FSHD patients carry deletions of an integral number of tandem 3.3 kilobase repeats, termed D4Z4, located on chromosome 4q35. Here, we find that in FSHD muscle 4q35 genes located upstream of D4Z4 are inappropriately over-expressed. We show that an element within D4Z4 specifically binds a multi-protein complex consisting of YY1, a known transcriptional repressor, HMGB2, an architectural protein, and nucleolin. We demonstrate that this multi-protein complex binds D4Z4 in vitro and in vivo and mediates transcriptional repression of 4q35 genes. Based upon these results we propose that deletion of D4Z4 leads to the inappropriate transcriptional derepression of 4q35 genes resulting in disease
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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