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The multiple affinities of alpha-dystroglycan
No full textThe dystroglycan (DG) adhesion complex is formed by the peripheral a-DG and the transmembrane a-DG,
both originating from the same precursor. a-DG plays a crucial role for tissue stability since it binds with high affinity a
variety of proteins and proteoglycans in many different cell types. One common molecular feature of most of the a-DG
ligands is the presence of LG domains that are likely to interact with some of the carbohydrates protruding from the
mucin-like region of a-DG. Every tissue is supposed to produce a specific a-DG harboring a particular sugar moiety that
will enable it to bind a specific ligand, but often several a-DG ligands are co-expressed within the same tissue. It is therefore very important to assess all these different interactions, ultimately measuring the affinity constants (KDs) underlying
them. Herein, we present an updated list of a-DG interactors, including non LG domains containing ligands, offering both
a historic perspective on the original contributions offered by several laboratories and an update on the different techniques used and the KD values obtained so far. For the cure of some muscular dystrophies, the reinstatement of a prominent affinity between a-DG and one of its vicarious ligands is becoming an increasingly popular choice for strengthening
the basement membrane-tissue connection. An update on the current available information about a-DG’s multiple, and often “concomitant” affinities, may be of interest for those wishing to better direct their molecular therapy approaches. A final paragraph is dedicated to comment on the evidence that an increase in affinity is not always advantageous
Role of gelatinases in pathological and physiological processes involving the dystrophin-glycoprotein complex
Get PDFDystrophin is a cytosolic protein belonging to a membrane-spanning glycoprotein complex, called dystrophin-glycoprotein complex (DGC) that is expressed in many tissues, especially in skeletal muscle and in the nervous system. The DGC connects the cytoskeleton to the extracellular matrix and, although none of the proteins of the DGC displays kinase or phosphatase activity, it is involved in many signal transduction pathways. Mutations in some components of the DGC are linked to many forms of inherited muscular dystrophies. In particular, a mutation in the dystrophin gene, leading to a complete loss of the protein, provokes one of the most prominent muscular dystrophies, the Duchenne muscular dystrophy, which affects 1 out of 3500 newborn males. What is observed in these circumstances, is a dramatic alteration of the expression levels of a multitude of metalloproteinases (MMPs), a family of extracellular Zn(2+)-dependent endopeptidases, in particular of MMP-2 and MMP-9, also called gelatinases. Indeed, the enzymatic activity of MMP-2 and MMP-9 on dystroglycan, an important member of the DGC, plays a significant role also in physiological processes taking place in the central and peripheral nervous system. This mini-review discusses the role of MMP-2 and MMP-9, in physiological as well as pathological processes involving members of the DGC.</p
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
Genetic engineering of dystroglycan in animal models of muscular dystrophy
Get PDFIn skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others) model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy
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
Insertion of a myc-tag within alpha-dystroglycan domains improves its biochemical and microscopic detection
No full textBackground: Epitope tags and fluorescent fusion proteins have become indispensable molecular tools for studies
in the fields of biochemistry and cell biology. The knowledge collected on the subdomain organization of the two
subunits of the adhesion complex dystroglycan (DG) enabled us to insert the 10 amino acids myc-tag at different
locations along the α-subunit, in order to better visualize and investigate the DG complex in eukaryotic cells.
Results: We have generated two forms of DG polypeptides via the insertion of the myc-tag 1) within a flexible
loop (between a.a. 170 and 171) that separates two autonomous subdomains, and 2) within the C-terminal domain
in position 500. Their analysis showed that double-tagging (the β-subunit is linked to GFP) does not significantly
interfere with the correct processing of the DG precursor (pre-DG) and confirmed that the α-DG N-terminal domain
is processed in the cell before α-DG reaches its plasma membrane localization. In addition, myc insertion in position
500, right before the second Ig-like domain of α-DG, proved to be an efficient tool for the detection and
pulling-down of glycosylated α-DG molecules targeted at the membrane.
Conclusions: Further characterization of these and other myc-permissive site(s) will represent a valid support for
the study of the maturation process of pre-DG and could result in the creation of a new class of intrinsic
doubly-fluorescent DG molecules that would allow the monitoring of the two DG subunits, or of pre-DG, in cells
without the need of antibodies
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