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Analysis of skin of nidogen deficient mouse models
No full textBasement membranes (BMs) are produced by complex interactions of laminins, collagen IV, perlecan and nidogen. Nidogen represents a small family of related proteins with two mammalian isoforms nidogen 1 and 2. Nidogens are ubiquitous BM components that have been proposed to play a key role for BM assembly. However, neither nidogen 1 nor nidogen 2 deficient mice showed BM defects suggesting overlapping functions of the two isoforms for the formation of BMs. Nidogen double null mice showed that this is indeed 1the case. These mice die shortly after birth showing various abnormalities particularly in the lung, heart and limb, directly related to BM defects. However, despite the fact that both nidogens are found in all BMs, some BMs in these mice appeared ultrastructurally normal. Mice lacking the high affinity binding site on the laminin g1 chain that is present in most laminin isoforms showed strikingly different phenotypes. While changes in the lung are common, these mice do not display cardiac changes and show a highly penetrant renal aplasia not seen in nidogen double null mice. We were therefore interested to analyse the skin phenotype in these mice in comparison to the nidogen double null mice to understand the biological contribution of the laminin nidogen interactions for nidogen function in skin development. Detailed analysis of the skin BMs revealed different phenotypes between the two mouse strains indicating differences in the role of nidogens and the laminin nidogen interaction for skin physiology
Role of the basement membrane proteins nidogen-1 and-2 for skin physiology and pathology
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Role of the basement membrane proteins nidogen-1 and-2 for skin physiology and pathology
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The absence of nidogen 1 does not affect murine basement membrane formation
No full textNidogen 1 is a highly conserved protein in mammals, Drosophila melanogaster, Caenorhabditis elegans, and ascidians and is found in all basement membranes. It has been proposed that nidogen 1 connects the laminin and collagen IV networks, so stabilizing the basement membrane, and integrates other proteins, including perlecan, into the basement membrane. To define the role of nidogen 1 in basement membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic stem cells and used these to derive mouse lines. Homozygous animals produce neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt abnormalities and are fertile, their basement membrane structures appearing normal. Nidogen 2 staining is increased in certain basement membranes, where it is normally only found in scant amounts. This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated, The results show that nidogen 1 is not required for basement membrane formation or maintenance
Loss of nidogen-1 and-2 results in syndactyly and changes in limb development
No full textNidogens are two ubiquitous basement membrane proteins produced mainly by mesenchymal cells. Nidogen-mediated interactions, in particular with laminin, collagen IV, and perlecan have been considered important in the formation and maintenance of the basement membrane. However, whereas mice lacking both nidogen isoforms or carrying mutations in the high affinity nidogen-binding site upon the laminin 1 chain have specific basement membrane defects in certain organs, particularly in the lung, characterization of these mice has also shown that basement membrane formation per se does not need nidogens or the laminin-nidogen interaction. Limb development requires the complex interplay of numerous growth factors whose expression is dependent upon the apical ectodermal ridge. Here, we show that lack of nidogen-1 and -2 results in a specific and time-limited failure in the ectodermal basement membrane of the limb bud. The absence of this basement membrane leads to aberrant apical ectodermal ridge formation. It also causes altered distribution of growth factors, such as fibroblast growth factors and leads to a fully penetrant soft tissue syndactyly caused by the dysregulation of interdigital apoptosis. Further, in certain animals more severe changes in bone formation occur, providing evidence for the interplay between growth factors and the extracellular matrix
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
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