1,720,976 research outputs found
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
Die Rolle von ARHGAP39 während der Zellmigration
Full text linkRho family GTPases are key regulators of cytoskeletal dynamics and control all aspects of cellular morphogenesis, ranging from migration to adhesion. They function as molecular switches that cycle between an inactive GDP-bound state and an active GTP-bound state, in which they can engage with numerous downstream effectors. Rho signalling requires tight spatiotemporal control which is mediated by in total 145 Rho guanine nucleotide exchange factors (RhoGEFs) and Rho GTPase activating proteins (RhoGAPs) in humans. These proteins encode a broad spectrum of targeting and protein interaction domains and thereby contribute specificity to Rho signalling.
During development, wound healing or metastasis, cells must change their positions within organs or the entire body. This is achieved by guided cell migration, where attractive or repulsive signals in the extracellular environment direct cells towards distinct positions. A well-studied class of guidance molecules is the SLIT ligand family that upon binding to their ROBO recep- tors directs repulsive migration in diverse tissues. The underlying processes are orchestrated by Rho GTPases, however, the downstream RhoGEFs and RhoGAPs that link the receptors to the GTPases are only poorly characterized and also have not been fully identified. Moreover, for the structurally distinct endothelial-specific ROBO4 receptor so far no regulator has been found at all.
In Drosophila melanogaster the RhoGAP Vilse/Crossgap, which is the homologue of the novel human RhoGAP ARHGAP39, has been linked to Robo signalling, as its depletion causes misrouting of tracheal ganglionic branches and axons in the central nervous system (CNS). Furthermore in a previous mass spectrometry screen for RhoGEF/GAP interactors (Müller et al., BioRxiv) ROBO4 was identified as binding partner for ARHGAP39. Motivated by the possible interaction of mammalian ARHGAP39 with all human ROBO receptors, I aimed to functionally characterize ARHGAP39 and to investigate its function in guided cell migration.
Together, my studies yielded insights into the role of ARHGAP39 in cell motility, both in randomly migrating cells and in SLIT2/ROBO-dependent guided migration, and provide the framework for future mechanistic studies
Temporal and Spatial Regulation of Rho GTPase Activity and Specificity
Full text linkRho GTPases are central signalling nodes in pathways that regulate cytoskeletal dynamics and control complex cellular functions such as cell adhesion, cell migration, and cell division. Rho GTPases are molecular switches: They exist in an active GTP-bound state and an inactive GDP-bound state. The transition between these states relies on the activating Rho guanine nucleotide exchange factors (RhoGEFs) and the inactivating Rho GTPase activating proteins (RhoGAPs). The number of signalling pathways up- and downstream of Rho GTPases is multitudinous and so is the large number of GAPs and GEFs, reflecting the diversity of physiological processes that involve Rho GTPase signalling. The human genome encodes as many as 150 of these regulatory proteins. Rho guanine nucleotide dissociation inhibitors (RhoGDIs) add an additional layer of regulation to the localization and activity of Rho GTPases. They bind to and stabilise Rho GTPases and thus create a soluble cytosolic pool of inactive Rho proteins.
Understanding the substrate specificity of the RhoGEFs and RhoGAPs is important in order to link them to their downstream signalling pathways. However, this has never been investigated in a systematic manner and is yet unknown for many GAPs and GEFs. I employed a previously assembled complete expression library of all full length RhoGEFs and RhoGAPs to systematically describe their activity towards any of the three paradigm Rho GTPases RhoA, Rac1 and Cdc42. For this purpose, I established a novel automated microscopic live cell RhoGEF and RhoGAP assay, based on second generation FRET biosensors for RhoA, Rac1, and Cdc42. The sensitivity of the assay was significantly enhanced by the modulation of cellular RhoGDI levels. I could show that the assay is very robust and suited to visualize subtle activity changes within living cells. I found that RhoGEFs have mostly exclusive activity, whereas RhoGAPs can have both exclusive and promiscuous activity. Furthermore, by applying semiquantitative image analysis I
could demonstrate that autoinhibition is a common mechanism by which RhoGEFs and RhoGAPs are regulated in cells.
I furthermore performed a family-wide analysis of RhoGEF and RhoGAP localization at focal adhesions and identified as many as 37 of them residing at these structures. Subsequent correlation of their substrate specificity suggests a key role of Rac1 in the regulation focal adhesion dynamics.
Along with activity, also the membrane association of Rho GTPases is tightly regulated. However, RhoGDI-mediated shuttling between membranes and rapid diffusion of Rho GTPases within membranes intuitively counteract spatially confined Rho signals and how Rho activity is locally initiated, maintained and terminated is not known. I analysed features that control the subcellular localisation of Rho GTPases and established the dynamic nature of Rho GTPase membrane residence. I could demonstrate that this dynamic membrane interaction is not primarily caused by RhoGDI but rather due to rapid lateral diffusion. In order to more precisely decipher the spatio-temporal signalling framework of Rho GTPases at the plasma membrane, I advanced the establishment of a single molecule tracking approach for Rho proteins. This assay can be used in future work to systematically investigate factors that regulate the spatial concentration of Rho GTPase activity.
Altogether, my study provides a systemic framework to place the Rho GTPases RhoA, Rac1, and Cdc42 into the complex network of up- and downstream signalling pathways and thus a basis for a better understanding of the spatio-temporal regulation of Rho GTPase signalling.Rho GTPasen sind zentrale Signalproteine in einem komplexen und weitreichenden Netzwerk intrazellulärer Signalwege, welche durch Organisation und Umbau des Zytoskeletts unter anderem Zellmigration, Zelladhäsion und Zellteilung kontrollieren. Als molekulare Schalter können Rho-Proteine einen aktiven GTP-gebundenen und einen inaktiven GDP-gebundenen Zustand einnehmen. Die Aktivierung der Rho GTPasen erfolgt durch GTP-Austauschfaktoren (GEFs), die Inaktivierung durch GTPase-aktivierende Proteine (GAPs). Entsprechend der Vielzahl der Signalwege, die durch Rho GTPasen kontrolliert werden, sind auch die regulatorischen RhoGEFs und RhoGAPs zahlreich, was die Komplexität der physiologischen Prozesse wider spiegelt, die durch Rho-Proteine reguliert werden. Das humane Genom enthält 150 dieser Rho-Regulatorproteine. Zusätzlich werden Rho GTPasen durch Guaninnukleotid-Dissoziations-Inhibitoren (RhoGDIs) reguliert. Diese binden an die posttranslationale Lipidmodifikation der Rho GTPasen und versetzen diese dadurch in einen löslichen Zustand, wodurch ein inaktiver zytosolischer Fundus an Rho GTPasen geschaffen wird.
Das Verständnis um die Substratspezifität von RhoGEFs und RhoGAPs ist unerlässlich, um diese in nachfolgende Signalwege einordnen zu können. Die Substratspezifität wurde jedoch noch nie umfassend und systematisch untersucht und ist für viele der RhoGEFs und RhoGAPs gänzlich unbekannt. Ich habe auf der Grundlage einer zuvor generierten Expressionsbibliothek systematisch die Aktivität aller RhoGEFs und RhoGAPs gegenüber jeder der drei wichtigen Rho GTPasen RhoA, Rac1 und Cdc42 untersucht. Zu diesem Zweck habe ich mithilfe der neuesten FRET Biosensoren für RhoA, Rac1 und Cdc42 eine neue, automatisierbare und auf Mikroskopie basierende Methode entwickelt. Die Sensitivität dieses Assays wurde zusätzlich, durch die gezielte Veränderung der RhoGDI Expressionslevel, signifikant gesteigert. Ich konnte darüber hinaus zeigen, dass der Assay zuverlässig selbst kleinste Aktivitätsveränderungen in lebenden Zellen wiedergeben kann. Dadurch konnte ich feststellen, dass RhoGEFs größtenteils Aktivität gegenüber einzelnen Rho GTPasen haben, wohingegen RhoGAPs sowohl Aktivität gegenüber einzelnen, als auch mehreren Rho GTPasen haben. Eine semiquantitative Analyse der Aktivitäten einiger RhoGEFs und RhoGAPs zeigte, dass die meisten dieser Regulatoren in Zellen autoinhibitorischen Regulationsmechanismen unterliegen.
Außerdem habe ich die gesamte Familie der RhoGEFs und RhoGAPs auf ihre Lokalisation an Fokalen Adhäsionen untersucht, wodurch ich 37 dieser Proteine identifiziert habe, die dort lokalisieren. Eine anschließende Korrelation mit der Substratspezifität hat ergeben, dass Rac1 vermutlich eine Schlüsselfunktion für die Regulation der Fokalen Adhäsionen hat.
Neben der Aktivität ist auch die Membranassoziation von Rho GTPasen genauestens reguliert. Der Transport von Rho GTPasen durch RhoGDI zwischen zellulären Membranen und ihre schnelle laterale Diffusion an Membranen widerspricht jedoch intuitiv einer räumlich begrenzten Anreicherung von Rho Aktivitäten. Wie daher die Signaltransduktion von Rho GTPasen lokal initiiert, aufrechterhalten und wieder beendet wird, ist nicht bekannt. Ich habe hier Strukturelemente untersucht, die die subzelluläre Lokalisation von Rho GTPasen steuern und festgestellt, dass Rho GTPasen sehr dynamisch an Membranen binden. Ich konnte darüber hinaus zeigen, dass diese dynamische Membraninteraktion nicht primär RhoGDI geschuldet ist, sondern eher durch schnelle laterale Diffusion zustande kommt. Um die zeitliche und räumliche Kontrolle der Prozesse, die der Rho Signaltransduktion an Membranen zugrunde liegen, präzise auftrennen zu können, habe ich die Entwicklung einer Einzelmolekülmikroskopie Methode für Rho-Proteine vorangetrieben. Mit dieser Methode wird das Ziel verfolgt werden systematisch nach Faktoren zu suchen, durch welche die räumliche Anreicherung von aktiven Rho GTPasen gewährleistet werden kann.
Mit dieser Studie habe ich systembiologisch relevante Informationen erarbeitet, durch die sich die Rho GTPasen RhoA, Rac1 und Cdc42 in dem weitgefächerten und hochkomplexen Netzwerk ihrer Signalwege platzieren lassen und habe dadurch eine wichtige Grundlage zum Verständnis der zeitlichen und räumlichen Regulation der Rho Signaltransduktion gelegt
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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