1,720,960 research outputs found
Growth Retardation, Loss of Desmosomal Adhesion, and Impaired Tight Junction Function Identify a Unique Role of Plakophilin 1 In Vivo
No full textDesmosomes mediate strong intercellular adhesion through desmosomal cadherins that interact with intracellular linker proteins including plakophilins (PKPs) 1-3 to anchor the intermediate filaments. PKPs show overlapping but distinct expression patterns in the epidermis. So far, the contribution of individual PKPs in differentially regulating desmosome function is incompletely understood. To resolve the role of PKP1 we ablated the PKP1 gene. Here, we report that PKP1(-/-) mice were born at the expected mendelian ratio with reduced birth weight, but they otherwise appeared normal immediately after birth. However, their condition rapidly declined, and the mice died within 24 hours, developing fragile skin with lesions in the absence of obvious mechanical trauma. This was accompanied by sparse and small desmosomes. Newborn PKP1(-/-) mice showed disturbed tight junctions with an impaired inside-out barrier, whereas the outside-in barrier was unaffected. Keratinocytes isolated from these mice showed strongly reduced intercellular cohesion, delayed tight junction formation, and reduced transepithelial resistance and reduced proliferation rates. Our study shows a nonredundant and essential role of PKP1 in desmosome and tight junction function and supports a role of PKP1 in growth control, a function that is crucial in wound healing and epidermal carcinogenesis
Regulation of PKP1´s function in intercellular adhesion, proliferation and barrier formation
Full text linkDesmosomen vermitteln eine starke interzelluläre Adhäsion über desmosomale Cadherine, die mit intrazellulären Proteinen interagieren, einschließlich Plakophilinen (PKPs) 1 und 3, welche Keratinfilamente verankern. Um die Rolle von PKP1 in der Stabilität von Desmosomen, Gewebedifferenzierung und Homöostase zu untersuchen, wurden PKP1 Knockout Mäuse generiert und charakterisiert. Diese Arbeit beschreibt PKP1 als essentiellen Regulator der epidermalen Homöostase, indem es die desmosomale interzelluläre Adhäsion, die Funktion von Tight Junctions sowie das Zellwachstum kontrolliert, eine Funktion, welche für die Wundheilung und epidermale Tumorentwicklung entscheidend ist. Außerdem wird PKP1 über den Insulin/IGF1-Signalweg reguliert. Nach Aktivierung des PI3K/Akt-Signalweges wird PKP1 durch Akt2 phosphoryliert, was zu einer cytoplasmatischen Akkumulation des Proteins führt, einhergehend mit verringerter interzellulärer Adhäsion, verstärkter Proliferation, Wundheilung und verankerungsunabhängigem Wachstum. Darüber hinaus zeigt diese Arbeit neue Isoform-spezifische Wechselwirkungen von PKP1 und 3 mit 14-3-3-Proteinen, welche die Stabilität von Desmosomen regulieren.Desmosomes mediate strong intercellular adhesion through desmosomal cadherins that interact with intracellular linker proteins including plakophilins (PKPs) 1 and 3 to anchor keratin filaments. PKPs show overlapping but distinct expression patterns in the epidermis. To resolve the role of PKP1 in desmosome stability, tissue differentiation and homeostasis, PKP1-knockout mice were generated and characterized. This work identifies PKP1 as a regulator of tissue homeostasis controlling desmosomal intercellular adhesion, tight junctions function and growth control, a function that is crucial in wound healing and epidermal carcinogenesis. Moreover, PKP1 is regulated by insulin/IGF1 signaling. Upon activation of the PI3K/Akt pathway, PKP1 is phosphorylated by Akt2 resulting in its predominant cytoplasmic accumulation correlated with reduced intercellular adhesion, enhanced proliferation, wound healing and anchorage-independent growth suggesting that PKP1 may contribute to tumorigenesis in a context-dependent way. In addition, this work shows novel isoform-specific interactions of PKPs and 14-3-3 proteins to control desmosome stability.vorgelegt von Katrin Rietsche
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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