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Modeling transcriptional RNA polymerase II clusters – formation, morphological changes, and dynamics
No full textFor the proper development of an organism, which requires, among other things,
a correct cell type differentiation, gene expression and an error-free transcription
process are indispensable. Most eukaryotic genes are transcribed by RNA
polymerase II (Pol II), which has two major control points: recruitment to
regulatory regions on chromatin, leading to paused Pol II, and pause release to
transcript elongation. These control steps are associated with the formation of
macromolecular clusters containing recruited Pol II. Although it has been suggested
that the clusters might be formed by liquid-liquid phase separation, the actual
mechanism of formation and interaction with DNA has remained poorly understood.
To investigate this in more detail, we used live and super-resolution microscopy
in zebrafish embryos, which revealed that clusters appear in various sizes and
shapes, depending on the apparent transcriptional activity at the cluster. To
further elucidate the basis of Pol II cluster formation we used these experimental
observations and incorporated a biophysical lattice kinetic Monte-Carlo (LKMC)
model, which revealed the cluster formation to be in line with the physical process
ofsurface condensationonregulatorychromatin. Bymeans ofthechemicalinhibitor
treatments in the experiments and recapitulated in the model, we found out
that recruited Pol II contributes to the condensate formation process on surfaces
provided by regulatory chromatin while elongating Pol II is excluded from these
condensates. In addition, previous work with mouse embryonic stem cells (mESCs)
has shown that the number of Pol II clusters that appear in the nucleus changes
during development. We wanted to check whether a similar behavior could also
be described by the proposed theoretical model. To this end, we used three
experimental models of differentiation and pluripotency exit (mouse embryonic
stem cells, fruit fly sperm precursor cells, and the natural development of zebrafish
embryos). We then used the experimental results to adjust our lattice model, which
captures the same stereotypical phenomenon during development: Pol II clusters
first become larger and rounder, then transition into unfolded shapes, and finally
split into small clusters. These observations can be summarized as a trajectory
in a three-dimensional cluster shape space with recruited Pol II, transcriptional
activity, and available condensation surface as the major coordinate axes. Finally,
the question arises, in how far these macromolecular clusters contribute to the
gene activation in general and how different genes interact with these clusters.
Our experiments have shown that some genes visit clusters and are activated as a
result, but overall, four possible combinations have emerged: visitor and non-visitor,
and activation and non-activation. Overall, this work sheds new light on the
mystery of the RNA polymerase II cluster formation mechanism, the morphological
changesofclustersandtheirinfluencingfactors, andclusterdynamicsincludingtheir
interaction with genes. In the long term, a better understanding of transcription
control by RNA Pol II clusters can help to find ways to prevent transcription errors
that can cause diseases or developmental malformations.Für die optimale Entwicklung eines Organismus, die unter anderem eine korrekte
Zelltypdifferenzierung erfordert, sind die Genexpression und ein fehlerfreier
Transkriptionsprozess unumgänglich. Die meisten eukaryotischen Gene werden
von der RNA-Polymerase II (Pol II) transkribiert, die über zwei wichtige
Kontrollpunkte verfügt: die Rekrutierung an regulatorische Regionen im Chromatin,
was zu einem pausierten Zustand von Pol II führt, und die Entlassung aus
dem pausierten Zustand hin zur Elongation. Diese Kontrollschritte werden mit
der Bildung von makromolekularen Clustern, die rekrutierte Pol II enthalten,
in Verbindung gebracht. Obwohl vermutet wurde, dass die Cluster durch
eine flüssig-flüssig-Phasentrennung gebildet werden könnten, ist der tatsächliche
Mechanismus der Bildung und der Interaktion mit der DNA bisher nur unzureichend
verstanden worden. Um dies genauer zu untersuchen, haben wir live und
hochauflösende Mikroskopie in Zebrafisch Embryonen eingesetzt. Dabei zeigte sich,
dass die Cluster in verschiedenen Größen und Formen auftreten, abhängig von
der offensichtlichen Transkriptionsaktivität an den Clustern. Um die Grundlagen
der Pol II Clusterbildung weiter aufzuklären, haben wir diese experimentellen
Beobachtungen genutzt und ein biophysikalisches lattice kinetic Monte-Carlo
(LKMC) Modell einbezogen, aus dem hervorging, dass die Clusterbildung in
Übereinstimmung mit dem physikalischen Prozess der Oberflächenkondensation auf
regulatorischemChromatininEinklangsteht.DurchdieBehandlungmitchemischen
Inhibitoren in den Experimenten und im Modell haben wir herausgefunden, dass
rekrutierte Pol II zur Bildung von Clustern auf Oberflächen beiträgt, die von
regulatorischem Chromatin bereitgestellt werden, und dass elongierende Pol II von
diesen Kondensaten ausgeschlossen ist. Darüber hinaus haben frühere Arbeiten mit
embryonalen Stammzellen der Maus (mESCs) gezeigt, dass sich die Anzahl der
Pol II Cluster, die im Laufe der Entwicklung im Zellkern entstehen, verändert.
Wir wollten überprüfen, ob ein ähnliches Verhalten auch durch das vorgeschlagene
theoretische Modell beschrieben werden kann. Zu diesem Zweck haben wir drei
experimentelle Modelle für die Differenzierung und den Austritt aus der Pluripotenz
(embryonale Stammzellen der Maus, Spermavorläuferzellen der Fruchtfliege und
die natürliche Entwicklung von Zebrafisch Embryonen) verwendet. Anhand der
experimentellen Ergebnisse haben wir dann unser Gittermodell angepasst, das
dasselbe stereotype Phänomen während der Entwicklung beschreibt: Pol II Cluster
werden zunächst größer und runder, gehen dann in eine entfaltete Form über
und teilen sich schließlich in kleine Cluster auf. Diese Beobachtungen lassen sich
als Trajektorie in einem dreidimensionalen Clusterformraum mit rekrutiertem Pol
II, Transkriptionsaktivität und verfügbarer Oberfläche als Hauptkoordinatenachsen
zusammenfassen. Schließlich stellt sich die Frage, inwieweit diese makromolekularen
ClusterzurGenaktivierungimAllgemeinenbeitragenundwieverschiedeneGenemit
diesen Clustern interagieren. Unsere Experimente haben gezeigt, dass einige Gene
die Cluster besuchen und dadurch aktiviert werden, aber insgesamt haben sich vier
mögliche Kombinationen herauskristallisiert: Besucher und Nicht-Besucher sowie
Aktivierung und Nicht-Aktivierung. Insgesamt wirft diese Arbeit ein neues Licht
auf das Geheimnis des Bildungsmechanismus von RNA-Polymerase II Clustern,
die morphologischen Veränderungen von Clustern und ihre Einflussfaktoren sowie
die Clusterdynamik einschließlich der Interaktion mit Genen. Langfristig kann
ein besseres Verständnis der Transkriptionskontrolle durch RNA-Pol II Cluster
dazu beitragen, Wege zur Vermeidung von Transkriptionsfehlern zu finden, die
Krankheiten oder andere Fehlbildungen während der Entwicklung verursachen
können
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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