186,624 research outputs found
Disassembly of shank and homer synaptic clusters is driven by soluble beta-amyloid(1-40) through divergent NMDAR-dependent signalling pathways
No full textDisruption of the postsynaptic density (PSD), a network of scaffold proteins located in dendritic spines, is thought to be
responsible for synaptic dysfunction and loss in early-stage Alzheimer’s disease (AD). Extending our previous demonstration
that derangement of the PSD by soluble amyloid-b (Ab) involves proteasomal degradation of PSD-95, a protein important
for ionotropic glutamate receptor trafficking, we now show that Ab also disrupts two other scaffold proteins, Homer1b and
Shank1, that couple PSD-95 with ionotropic and metabotropic glutamate receptors. Treatment of fronto-cortical neurons
with soluble Ab results in rapid (within 1 h) and significant thinning of the PSD, decreased synaptic levels of Homer1b and
Shank1, and reduced synaptic mGluR1 levels. We show that de novo protein synthesis is required for the declustering effects
of Ab on Homer1b (but not Shank1) and that, in contrast to PSD-95, Ab-induced Homer1b and Shank1 cluster disassembly
does not depend on proteasome activity. The regulation of Homer1b and Shank1 by Ab diverges in two other respects: i)
whereas the activity of both NMDAR and VDCC is required for Ab-induced declustering of Homer1b, Ab-induced
declustering of Shank1 only requires NMDAR activity; and ii) whereas the effects of Ab on Homer1b involve engagement of
the PI-3K pathway and calcineurin phosphatase (PP2B) activity, those on Shank1 involve activation of the ERK pathway. In
summary, soluble Ab recruits discrete signalling pathways to rapidly reduce the synaptic localization of major components
of the PSD and to regulate the availability of mGluR1 in the synapse
Soluble beta-amyloid1-40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses
No full textAmyloid- (A) has been implicated in memory loss and disruption of synaptic plasticity observed in early-stage Alzheimer’s disease. Recently, it has been shown that solubleA oligomers target synapses in cultured rat hippocampal neurons, suggesting a direct role ofA in the regulation of synaptic structure and function. Postsynaptic density-95 (PSD-95) is a postsynaptic scaffolding protein that plays a critical role in synaptic plasticity and the stabilization of AMPA (AMPARs) and NMDA (NMDARs) receptors at synapses. Here, we show that exposure of cultured cortical neurons to soluble oligomers of A1– 40 reduces PSD-95 protein levels in a dose- and time-dependent manner and that theA11– 40-dependent decrease in PSD-95 requiresNMDARactivity.Wealso show that the decrease in PSD-95 requires cyclin-dependent kinase 5 activity and involves the proteasome pathway. Immunostaining analysis of cortical cultured neurons revealed that A treatment induces concomitant decreases in PSD-95 at synapses and in the surface expression of theAMPARglutamate receptor subunit 2. Together, these data suggest a novel pathway by which A triggers synaptic dysfunction, namely, by altering the molecular composition of glutamatergic synapses
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
No full textWe 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
Dr. Edward P. Wimberly, ITC, July 2011
No full textThis video is a conversation with Dr. Edward P. Wimberly. Dr. Wimberly talks about his book, "No Shame in Wesley's Gospel: A Twenty-First Century Pastoral Gospel". Brad Ost, AUC Woodruff Library, is the interviewer
Author Rights and Scholarly Publishing
No full textOriginally posted at
http://blog.library.gsu.edu/2014/10/24/author-rights-and-scholarly-publishing/</p
Stability maps for columnar structures
No full textWe have previously explored the hysteresis and reversibility of transitions between ordered packings of soft spheres of diameter d in cylindrical channels of diameter D [A. Mughal, J. Winkelmann, D. Weaire, S. Hutzler, Phys. Rev. E 98, 043303 (2018)]. Here we extend these initial results to include transitions between all columnar structures without inner spheres (i.e. packings in which all of the spheres are in contact with the cylindrical boundary). These results can be represented by a directed network showing permissible transitions between structures. From the hard sphere limit we deduce that there are two different types of transitions, reversible and irreversible. We explore the nature of these transitions for soft spheres as a function of pressure and due to changes in the ratio D/d. These results are illustrated by the use of schematic diagrams, indicating the topological features of each transition. Specific cases are tabulated and can be understood by reference to the appropriate schematic diagram.</p
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