1,721,103 research outputs found
Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1
The cAMP-dependent protein kinase A (PKA) regulates various cellular functions in health and disease. In endothelial cells PKA activity promotes vessel maturation and limits tip cell formation. Here, we used a chemical genetic screen to identify endothelial-specific direct substrates of PKA in human umbilical vein endothelial cells (HUVEC) that may mediate these effects. Amongst several candidates, we identified ATG16L1, a regulator of autophagy, as novel target of PKA. Biochemical validation, mass spectrometry and peptide spot arrays revealed that PKA phosphorylates ATG16L1α at Ser268 and ATG16L1β at Ser269, driving phosphorylation-dependent degradation of ATG16L1 protein. Reducing PKA activity increased ATG16L1 protein levels and endothelial autophagy. Mouse in vivo genetics and pharmacological experiments demonstrated that autophagy inhibition partially rescues vascular hypersprouting caused by PKA deficiency. Together these results indicate that endothelial PKA activity mediates a critical switch from active sprouting to quiescence in part through phosphorylation of ATG16L1, which in turn reduces endothelial autophagy.sponsorship: [
"Europees Fonds voor Regionale Ontwikkeling G.0742.15N Holger Gerhardt",
"Else-Kroener Stiftung 2014_A26 Pavel Nedvetsky Holger Gerhardt",
"European Research Council 311719 REshape Holger Gerhardt",
"Deutsche Forschungsgemeinschaft DFG KL1415/7-1 Enno Klussmann",
"Deutsche Forschungsgemeinschaft 394046635 - SFB 1365 Enno Klussmann",
"Bundesministerium fur Bildung und Forschung 16GW0179K Enno Klussmann",
"Vlaams Instituut voor Biotechnologie Tech Watch Q3 2015 Pavel Nedvetsky Holger Gerhardt",
"The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication."
] (Europees Fonds voor Regionale Ontwikkeling|G.0742.15N, Else-Kroener Stiftung|2014_A26, European Research Council|311719, Deutsche Forschungsgemeinschaft|DFG KL1415/7-1, Deutsche Forschungsgemeinschaft|394046635 - SFB 1365, Bundesministerium fur Bildung und Forschung|16GW0179K, Vlaams Instituut voor Biotechnologie|Tech Watch Q3 2015)status: Publishe
Replication: Concentration Bias in Intertemporal Choice
Replication of "Concentration Bias in Intertemporal Choice" by
Markus Dertwinkel-Kalt, Holger Gerhardt, Gerhard Riener, Frederik Schwerter & Louis Stran
Replication: Concentration Bias in Intertemporal Choice
Replication of "Concentration Bias in Intertemporal Choice" by
Markus Dertwinkel-Kalt, Holger Gerhardt, Gerhard Riener, Frederik Schwerter & Louis Stran
Replication: Concentration Bias in Intertemporal Choice
Replication of "Concentration Bias in Intertemporal Choice" by
Markus Dertwinkel-Kalt, Holger Gerhardt, Gerhard Riener, Frederik Schwerter & Louis Stran
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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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