1,720,959 research outputs found
Bace1 processing of NRG1 type III produces a myelin‐inducing signal but is not essential for the stimulation of myelination
No full textNeuregulin 1 type III/ErbB signaling is crucial for Schwann cell colonization of sympathetic axons
Full text linkAnalysis of Schwann cell (SC) development has been hampered by the lack of growing axons in many commonly used in vitro assays. As a consequence, the molecular signals and cellular dynamics of SC development along peripheral axons are still only poorly understood. Here we use a superior cervical ganglion (SCG) explant assay, in which axons elongate after treatment with nerve growth factor (NGF). Migration as well as proliferation and apoptosis of endogenous SCG-derived SCs along sympathetic axons were studied in these cultures using pharmacological interference and time-lapse imaging. Inhibition of ErbB receptor tyrosine kinases leads to reduced SC proliferation, increased apoptosis and thereby severely interfered with SC migration to distal axonal sections and colonization of axons. Furthermore we demonstrate that SC colonization of axons is also strongly impaired in a specific null mutant of an ErbB receptor ligand, Neuregulin 1 (NRG1) type III. Taken together, using a novel SC development assay, we demonstrate that NRG1 type III serves as a critical axonal signal for glial ErbB receptors that drives SC development along sympathetic axons
Conditional activation of NRG1 signaling in the brain modulates cortical circuitry
Full text linkNeuregulin (NRG) 1 contains an epidermal growth factor (EGF)-like signaling domain
and serves as a ligand for receptor tyrosine kinases of the ErbB family. ErbB4, the
main neuronal NRG1 receptor in the brain, is enriched in GABAergic interneurons.
NRG1/ErbB4 signaling regulates different aspects of nervous system development
and synaptic plasticity in the mature brain. Variants of the human NRG1 and ERBB4
genes are genetic risk factors for schizophrenia, and inhibitory network dysfunctions
have been implicated in schizophrenia. For NRG1 most of the at-risk haplotypes are
located in non-coding regions, implicating that expression of NRG1 isoforms might
be altered in SZ. In line with this, increased NRG1 expression and ErbB4
hyperphosphorylation was observed in postmortem brains of schizophrenia patients,
suggesting that NRG1/ErbB4 hyperstimulation represents a possible
pathomechanisms in schizophrenia. To test this hypothesis several NRG1 loss- and
gain-of-function mouse models were employed to examine effects of altered NRG1
signaling on nervous system development and adult brain functions.
Conditional ablation of NRG1 in the embryonic cortex (Emx-Cre*Nrg1f/f mice) had no
effect on cortical development, whereas pan-neuronal overexpression of the CRDNRG1
isoform in transgenic mice lead to ErbB4 hyperactivation, altered numbers of
cortical interneurons, changes in dendritic spine morphology, ventricular
enlargement, increased anxiety-like behavior, and impaired sensorimotor gating.
These data suggest that the human NRG1 risk haplotypes exert a gain-of-function
effect.
To study NRG1/ErbB4 hyperstimulation in a more selective in vivo model, a
‚conditional’ transgenic mouse line (Stop-Nrg1) was generated, which allows Cre
recombinase-mediated CRD-NRG1 overexpression. This mouse line was examined
in combination with different Cre ‚driver’ lines to model distinct temporal and spatial
aspects of CRD-NRG1 overexpression in the brain. Postnatal onset of CRD-NRG1
overexpression had only minor effects on nervous system development and
behavior, whereas early embryonic onset of NRG1 hyperstimulation lead to
hyperactivity, consistent with the neurodevelopmental hypothesis of schizophrenia.
Cortical-restricted CRD-NRG1 overexpression had no effect on ventricular size or
sensorimotor gating, indicating functions of CRD-NRG1 signaling in subcortical
networks. Finally, CRD-NRG1 was present in synaptosomal fractions and appears to
recruit LIMK1-cofilin signaling, providing a potential mechanism for the regulation of
dendritic spine dynamics
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
- …
