1,721,078 research outputs found
Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant
No full textApoptosis is not required for mammalian neural tube closure
No full textApoptotic cell death occurs in many tissues during embryonic development and appears to be essential for processes including digit formation and cardiac outflow tract remodeling. Studies in the chick suggest a requirement for apoptosis during neurulation, because inhibition of caspase activity was found to prevent neural tube closure. In mice, excessive apoptosis occurs in association with failure of neural tube closure in several genetic mutants, but whether regulated apoptosis is also necessary for neural tube closure in mammals is unknown. Here we investigate the possible role of apoptotic cell death during mouse neural tube closure. We confirm the presence of apoptosis in the neural tube before and during closure, and identify a correlation with 3 main events: bending and fusion of the neural folds, postfusion remodeling of the dorsal neural tube and surface ectoderm, and emigration of neural crest cells. Both Casp3 and Apaf1 null embryos exhibit severely reduced apoptosis, yet neurulation proceeds normally in the forebrain and spine. In contrast, the mutant embryos fail to complete neural tube closure in the midbrain and hindbrain. Application of the apoptosis inhibitors z-Vad-fmk and pifithrin-alpha to neurulation-stage embryos in culture suppresses apoptosis but does not prevent initiation or progression of neural tube closure along the entire neuraxis, including the midbrain and hindbrain. Remodeling of the surface ectoderm to cover the closed tube, as well as delamination and migration of neural crest cells, also appear to be normal in the apoptosis-suppressed embryos. We conclude that apoptosis is not required for neural tube closure in the mouse embryo
Planar cell polarity signalling and development of the early mammalian nervous system
Get PDFThe vertebrate planar cell polarity (PCP) pathway is an evolutionarily conserved signalling cascade which regulates numerous developmental processes. This thesis investigates the role of PCP signalling in two events, mammalian spinal neurulation and neural crest (NC) cell migration. In mouse embryos PCP signalling is required for initiation of neural tube closure, via regulation of midline convergent extension (CE). In this thesis, a genetic modifying role for the loop-tail (Vangl2Lp) mutation is shown to also predispose to failure of low spinal neurulation. Mutations in the core PCP gene Vangl2 increase the frequency and severity of spina bifida in the grainyhead-like-3 hypomorph curly tail (Grhl3ct/ct), a model of partially-penetrant NTDs. Affected Vangl2Lp/+;Grhl3ct/ct embryos exhibit abnormalities of axis elongation, suggesting a role for CE in spinal neurulation. Investigations of the mechanism underlying the Lp/ct interaction reveal two distinct types of effect: 1) Effects of expression of Vangl2Lp and Grhl3ct in different tissues: Vangl2 regulates midline CE and Grhl3 regulates proliferation of tail bud progenitors. These mutant effects likely summate, leading to severe spina bifida; 2) Cell-autonomous effects of Vangl2Lp and Grhl3ct co-expression in the same tissue: conditional genetic experiments suggest a requirement for Vangl2 and Grhl3 within the same cells during neurulation and evidence for a molecular interaction at the level of Rho-GTPase signalling is presented. In amphibia and fish, early NC migration is PCP-dependent, but this has not yet been studied in mammals. Vangl2Lp/Lp embryos display normal NC cell migration, despite many severe PCP-related defects, and migration of Vangl2Lp/Lp NC in vitro is comparable to Vangl2+/+. The closely related gene Vangl1 does not appear to compensate for loss of Vangl2. Acute down-regulation of Vangl2 specifically in the NC lineage does not cause migratory defects. Hence, the core PCP pathway is not required for early NC migration in the mouse
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
Cell cycle heterogeneity as a regulator of epithelial bending during neural tube closure
Get PDFDuring neurulation, the neural plate bends around the median hinge point (MHP), overlying the notochord. MHP cells spend more time in G1/S-phase of the cell cycle than lateral cells, and this is associated with adoption of a wedged cell shape due to interruption of interkinetic nuclear migration. Clustering of wedge shaped cells in the MHP is suggested to drive midline bending. To determine the mechanism underlying the prolonged cell cycle in the MHP, I examined the mRNA expression of cell cycle inhibitors, and found the cyclin-dependent-kinase-inhibitors (CDKIs), p21, p27 and p57, to be expressed in midline cells. p21-/- mice, which exhibit MHPs, show upregulation of p57 mRNA in midline cells, supporting the hypothesis of a redundant relationship between p21 and p57 during neural plate bending. Detailed cell cycle analysis was performed in p21-/- and p21+/+ embryos by sequential injections of two thymidine analogues, IdU and BrdU. p21-/- MHP cells spend significantly less time in S-phase compared to wild-type littermates, suggesting that p21 is responsible for the prolonged S-phase in the MHP. In the absence of p21, S-phase length in the MHP and lateral cells is equivalent. Overexpression of CIP/KIP genes in the midline of cultured embryos did not increase the proportion of basal nuclei, a measure of wedge shaped cells. Electroporation of p57 siRNA abolished p57 mRNA from the neural plate and notochord of p21-/- embryos but did not prevent MHP formation. Collectively, the results indicate that p21 is responsible for the prolongation of S-phase in the MHP but is not necessary for MHP formation. There is possible redundancy between p21 and p57 in the MHP. However, loss of both p21 and p57 is not sufficient to prevent MHP formation. Furthermore, a prolonged S-phase in the midline cells of the neural plate is not necessary for MHP formation
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
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