1,720,956 research outputs found
Evidence for protein phosphatase inhibitor-1 playing an amplifier role in β-adrenergic signaling in cardiac myocytes
No full textThe protein phosphatase inhibitor-1 (PPI-1) inhibits phosphatase type-1 (PP1) only when phosphorylated by protein kinase A and could play a pivotal role in the phosphorylation/dephosphorylation balance. Rat cardiac PPI-1 was cloned by reverse transcriptase-polymerase chain reaction, expressed in Eschericia coli, evaluated in phosphatase assays, and used to generate an antiserum. An adenovirus was constructed encoding PPI-1 and green fluorescent protein (GFP) under separate cytomegalovirus promotors (AdPPI-1/GFP). A GFP-only virus (AdGFP) served as control. Engineered heart tissue (EHT) from neonatal rat cardiomyocytes and adult rat cardiac myocytes (ARCMs) were used as model systems. PPI-1 expression was determined in human ventricular samples by Northern blots. Compared with AdGFP, AdPPI-1/GFP-infected neonatal rat cardiomyocytes displayed a 73% reduction in PP1 activity. EHTs infected with AdPPI-1/GFP exhibited a fivefold increase in isoprenaline sensitivity. AdPPI-1/GFP-infected ARCMs displayed enhanced cell shortening as well as enhanced phospholamban phosphorylation when stimulated with 1 nM isoprenaline. PPI-1 mRNA levels were reduced by 57±12% in failing hearts with dilated and ischemic cardiomyopathy (n=8 each) compared with nonfailing hearts (n=8). In summary, increased PPI-1 expression enhances myocyte sensitivity to isoprenaline, indicating that PPI-1 acts as an amplifier in β-adrenergic signaling. Decreased PPI-1 in failing human hearts could participate in desensitization of the cAMP pathway
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
Zur Bedeutung des Protein-Phosphatase-Inhibitor-1 in der menschlichen Herzinsuffizienz
No full textIn der Herzinsuffizienz führt die chronische Erhöhung des Sympathikotonus zur Desensitivierung des ß-adrenergen Signalweges wodurch nachfolgend die Phosphorylierung von regulatorischen Phosphoproteinen verändert wird. Der Phosphorylierungszustand wichtiger Phosphoproteine kann über eine Aktivierung der entsprechenden Kinase oder eine Hemmung der entsprechenden Phosphatase verändert werden. Die Proteinphosphatasen werden unter anderem durch inhibitorische Proteine reguliert. Der Protein-Phosphatase-Inhibitor-1 stellt eines dieser inhibitorischen Proteine dar. Der Inhibitor-1 wird durch die cAMP abhängige Proteinkinase A (PKA) an Threonin35
phosphoryliert und hemmt ausschließlich in diesem Zustand die im Herzen vorherrschende Proteinphosphatase-1 (PP1).
Um Aufschluss über eine potentielle pathophysiologische Bedeutung von Inhibitor-1 bei der menschlichen Herzinsuffizienz zu erhalten, sollten die Proteinmenge sowie die PKA-Phosphorylierung (Aktivität) von Inhibitor-1 in insuffizienten menschlichen Herzen quantifiziert und diese mit nicht-insuffizienten Spenderherzen verglichen werden. Andererseits sollte untersucht werden, welche Proteinphosphatase für die Dephosphorylierung des Inhibitor-1 an Threonin35
verantwortlich ist.
Während dieser Analysen zeigte sich, dass die immunologische Detektion von Inhibitor-1 mit den bisherigen verfügbaren Antikörpern weder histologisch noch in SDS-Standardhomogenaten möglich ist. Da Inhibitor-1 eine hohe Hitzestabilität und Säurelöslichkeit ausweist, gelang durch Trichloressigsäure (TCA)-Fällung und Kochen eine mehr als 500-fache Aufkonzentrierung. Mit Hilfe von Verdünnungsreihen solcher TCA-Extrakte parallel zu rekombinanten Inhibitor-1 konnte die Inhibitor-1 Proteinkonzentration in menschlichen Herzproben bestimmt werden. Diese Untersuchung ergab, dass die Inhibitor-1 Konzentration im linksventrikulären Myokard mit ~120 nM deutlich über der IC50 (~1 nM) der PP1 lag und somit ausreichend war, um die kardiale PP1 effizient zu hemmen. Der Vergleich insuffizienter und nicht-insuffizienter Herzen ergab, dass die Inhibitor-1 Proteinmenge um 57% und der PKA-Phosphorylierungsgrad um 72% in insuffizientem Myokard erniedrigt sind. Außerdem konnte eine enge Korrelation zwischen dem Phosphorylierungsgrad des Inhibitors-1 mit dem von Phospholamban, welches die Aufnahme von Ca2+ in das sarkoplasmatische Retikulum in der Diastole steuert, gezeigt werden. Dies deutete auf einen direkten kausalen Zusammenhang zwischen den Funktionszuständen beider Proteine hin.
Mit Hilfe von spezifischen chemischen Phosphatase-Inhibitoren und phosphospezifischen Antikörpern konnte mittels Western Blot gezeigt werden, dass in Herzmuskelzellen der neugeborenen Ratte die Blockade der Ca2+-abhängigen Typ 2B Phosphatase (Calcineurin) zu einer gesteigerten Inhibitor-1 Phosphorylierung an Threonin35 führt. Dieser Befund
korrelierte mit einer erhöhten Phosphorylierung des funktionell nachgeschalteten Phospholambans, das kein Substrat von Calcineurin ist.
Diese Arbeit zeigt erstmalig, dass Inhibitor-1 in der menschlichen Herzinsuffizienz reguliert ist und impliziert, dass die stark verminderte Proteinmenge und Phosphorylierung von Inhibitor-1 als Verstärkerelement der ß-adrenergen Signalkaskade zum Wirkungsverlust von Katecholaminen bei der Herzinsuffizienz beitragen könnten. Die hier dargestellten Befunde implizieren ferner, dass Calcineurin Inhibitor-1 in vivo dephosphorylieren und somit deaktivieren kann. Über Calcineurin könnte Inhibitor-1 einen potentiell wichtigen cross talk zwischen cAMP- und Ca2+
-Signalwege im Herzen vermitteln
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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