1,720,954 research outputs found
Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway
No full textAxonal transport of mitochondria and synaptic vesicle precursors via kinesin motor proteins is essential to keep integrity of axons and synapses. Disturbance of axonal transport is an early sign of neuroinflammatory and neurodegenerative diseases. Treatment of cultured neurons by the inflammatory cytokine tumor necrosis factor-alpha (TNF) stimulated phosphorylation of c-Jun N-terminal kinase (JNK) in neurites. TNF treatment induced dissociation of the heavy chain kinesin family-5B (KIF5B) protein from tubulin in axons but not cell bodies as determined by lifetime-based Forster resonance energy transfer (FRET) analysis. Dissociation of KIF5B from tubulin after TNF treatment was dependent on JNK activity. Furthermore, TNF inhibited axonal transport of mitochondria and synaptophysin by reducing the mobile fraction via JNK. Thus, TNF produced by activated glial cells in inflammatory or degenerative neurological diseases acts on neurites by acting on the kinesin-tubulin complex and inhibits axonal mitochondria and synaptophysin transport via JNK.-Stagi, M., Gorlovoy, P., Larionov, S., Takahashi, K., and Neumann, H. Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway
Die Rolle des Mikrotubuli-assoziierten Proteins Tau in entzündungsbedingten axonalen Schäden
No full textIntrazelluläre Aggregate des
Mikrotubuli–assoziierten Proteins tau sind der Hauptbestandteil der
neurofibrillären Tangles in Neuriten bei Alzheimer-Krankheit und
anderen neurodegenerative Tauopathien. Der genaue molekulare
Mechanismus der Tau-Aggregation ist nicht bekannt. Genetische
Mutationen in tau und extrazelluläre Aggregate des
Amyloid-ß-Proteins scheinen die Aggregation von tau zu fördern und
eine mögliche Krankheitsursache zu sein. Um Herauszufinden ob
inflammatorische Mediatoren, wie tumor necrosis factor-alpha
(TNF-alpha), die von Mikrogliazellen freigesetzt werden, einen
Einfluss auf die Tau-Aggregation in Neuronen haben, analysieren wir
primäre Neuronen transfektiert mit einen 441 Aminosäure lange
tau-Protein fusioniert mit verschidene Variationen des grün
fluoreszierenden Proteins (GFP, Cerulean, Citrine) mit fluorescence
lifetime-based Förster resonance energy transfer (FRET). Primäre
Neuronen kotransfiziert mit Cerulean-tau und Citrine-tau wurden mit
FLIM analysiert um jegliche Dimerisierung oder Polymerisation von
tau mit FRET zu detektieren. In unbehandelten Neuronen war keine
Dimerisierung oder Polymerisation erkennbar. Nach der Behandlung
der Neuronen für 3 Stunden mit TNF-alpha, war vor allem in der
Neuriten eine Dimerisierung / Polymerisation von Citrine-tau and
Cerulean-tau zu erkennen. Unsere Ergebnisse zeigen, dass
inflammatorische Mediatoren wie TNF-alpha, vor allem in
neurodegenerativen Erkrankungen Aggregation von tau induzieren
können und wahrscheinlich in die ersten Schnitte der Bildung von
neurofibrillären Tangles involviert sind. Die Hemmung der TNF-alpha
induziereten Aggregation von tau könnte eine vielversprechende
Therapiemöglichkeit der Alzheimer-Krankheit sein.Intracellular aggregates of the
microtubule associated protein tau in neurites are the major
component of neurofibrillary tangles in Alzheimer's disease and
other neurodegenerative tauopathies. The exact molecular mechanism
of tau aggregation is not known. Genetic mutations of tau and
extracellular deposits of amyloid-ß peptide oligomers have been
shown to facilitate aggregation of tau and to be disease-causative.
To analyze whether microglial inflammatory mediators such as tumor
necrosis factor-alpha (TNF-α) have any effects on aggregation of
tau in neurons, we performed fluorescence lifetime-based Förster
resonance energy transfer (FRET) analysis of cultured primary
neurons transfected with the 441 amino acid long human tau (tau)
fused to the green fluorescent protein variants (GFP, Cerulean and
Citrine). Primary neurons cotransfected with Citrine-tau and
Cerulean-tau were analyzed by FLIM to detect any FRET reflecting
dimerization or polymerization of tau. Dimerization or
polymerization of cotransfected Citrine-tau / Cerulean-tau was not
detected in untreated neurons. Treatment of neurons with TNF-α for
3 hours resulted in dimerization or polymerization of Citrine-tau
and Cerulean-tau preferentially in neurites. Our data demonstrate
that inflammatory mediators like TNF-α, prevalent in degenerative
brain diseases, can induce aggregation of tau and might be involved
in the first steps of neurofibrillary tangle formation. The
inhibition of the TNF-α mediated aggregation of tau could be a very
promising therapeutical strategy in Alzheimer disease
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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