1,721,095 research outputs found
Mechanisms of axonal degeneration in EAE - lessons from CNTF and MHC I knockout mice
No full textThe major pathological hallmarks of multiple sclerosis (MS) comprise inflammation, demyelination with associated gliosis and axonal damage, which most likely correlates with persisting disability. Axonal damage can occur by several mechanisms. This article focuses on myelin disintegration and direct immune attack on axons by CD8-positive T-cells as two possible scenarios for axonal injury. As protoypic models, we investigated experimental autoimmune encephalomyelitis (EAE) in ciliary neurotrophic factor gene knockout mice (CNTF-/- mice) with severe myelin pathology and EAE in beta-2 microglobulin gene knockout mice (beta 2m-/- mice) lacking CD8-positive T-cells. The results from these studies indicate that the trigger attack for axonal injury even in a well-defined experimental design can be multi-facetted. No single factor seems to be absolutely necessary for the initiation of the process, but they rather act in concert and orchestrate tissue destruction, inflammation and regeneration. Some mechanisms of primary or secondary axonal damage may be shared between inflammatory and degenerative diseases of the nervous system, thereby establishing a link which might be of importance for future therapeutic strategies. (c) 2005 Elsevier B.V. All rights reserved
Ciliary neurotrophic factor (CNTF): physiologische und pharmakologische Effekte in der Retina
No full textContribution of Ca2+-permeable AMPA/KA receptors to glutamate-induced Ca2+ rise in embryonic lumbar motoneurons in situ
No full textIntracellular Ca2+ ([Ca2+](i)) was fluorometrically measured with fura-2 in lumbar motoneurons of acutely isolated spinal cord slices from embryonic rats. In ester-loaded cells, bath-applied glutamate (3 mu M to 1 mM) evoked a [Ca2+](i) increase by up to 250 nM that was abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 2-amino-5-phosphonovalerate (APV). CNQX or APV alone reduced the response by 82 and 25%, respectively. The glutamatergic agonists kainate (KA), quisqualate (QUI), and S-alpha-amino-3-hydroxy-5-methyl-4-isoxalone (S-AMPA) evoked a similar [Ca2+](i) transient as glutamate. N-methyl-D-aspartate (NMDA) was only effective to increase [Ca2+](i) in Mg2+-free saline, whereas [1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid([1S,3R]ACPD) had no effect. The glutamate-induced [Ca2+](i) rise was suppressed in Ca2+-free superfusate. Depletion of Ca2+ stores with cyclopiazonic acid (CPA) did not affect the response. Thirty-six percent of the [Ca2+](i) increase in response to membrane depolarization induced by a 50 mM K+ solution persisted on combined application of the voltage-gated Ca2+ channel blockers nifedipine, omega-conotoxin-GVIA and omega-agatoxin-IVA. In fura-2 dialyzed motoneurons, the glutamate-induced [Ca2+](i) increase was attenuated by similar to 70% after changing from current to voltage clamp. Forty percent of the remaining [Ca2+], transient and 20% of the concomitant inward current of 0.3 nA were blocked by Joro spider toxin-3 (JSTX). The results show that voltage-gated Ca2+ channels, including a major portion of R-type channels, constitute the predominant component of glutamate-induced [Ca2+](i) rises. NMDA and Ca2+-permeable KA/AMPA receptors contribute about equally to the remaining component of the Ca2+ rise. The results substantiate previous assumptions that Ca2+ influx through JSTX-sensitive KA/AMPA receptors is involved in (trophic) signaling in developing motoneurons
Contribution of Ca2+-permeable AMPA/KA receptors to glutamate-induced Ca2+ rise in embryonic lumbar motoneurons in situ
No full textIntracellular Ca2+ ([Ca2+](i)) was fluorometrically measured with fura-2 in lumbar motoneurons of acutely isolated spinal cord slices from embryonic rats. In ester-loaded cells, bath-applied glutamate (3 mu M to 1 mM) evoked a [Ca2+](i) increase by up to 250 nM that was abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 2-amino-5-phosphonovalerate (APV). CNQX or APV alone reduced the response by 82 and 25%, respectively. The glutamatergic agonists kainate (KA), quisqualate (QUI), and S-alpha-amino-3-hydroxy-5-methyl-4-isoxalone (S-AMPA) evoked a similar [Ca2+](i) transient as glutamate. N-methyl-D-aspartate (NMDA) was only effective to increase [Ca2+](i) in Mg2+-free saline, whereas [1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid([1S,3R]ACPD) had no effect. The glutamate-induced [Ca2+](i) rise was suppressed in Ca2+-free superfusate. Depletion of Ca2+ stores with cyclopiazonic acid (CPA) did not affect the response. Thirty-six percent of the [Ca2+](i) increase in response to membrane depolarization induced by a 50 mM K+ solution persisted on combined application of the voltage-gated Ca2+ channel blockers nifedipine, omega-conotoxin-GVIA and omega-agatoxin-IVA. In fura-2 dialyzed motoneurons, the glutamate-induced [Ca2+](i) increase was attenuated by similar to 70% after changing from current to voltage clamp. Forty percent of the remaining [Ca2+], transient and 20% of the concomitant inward current of 0.3 nA were blocked by Joro spider toxin-3 (JSTX). The results show that voltage-gated Ca2+ channels, including a major portion of R-type channels, constitute the predominant component of glutamate-induced [Ca2+](i) rises. NMDA and Ca2+-permeable KA/AMPA receptors contribute about equally to the remaining component of the Ca2+ rise. The results substantiate previous assumptions that Ca2+ influx through JSTX-sensitive KA/AMPA receptors is involved in (trophic) signaling in developing motoneurons
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
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