1,721,003 research outputs found
Functional analyses of mitotic microtubule-binding complexes
No full textThesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.Mitosis is the process by which a single cell divides to form two identical daughter cells. Each daughter cell must inherit a full complement of the genetic material. Thus, a critical aspect of mitosis is the faithful segregation of each duplicated chromosome. Chromosome segregation is achieved through the attachment of a chromosome-localized macromolecular complex, termed the kinetochore, to microtubules. Microtubules are dynamic polymers comprised of tubulin heterodimers. The successful execution of mitosis additionally depends on the organization of the microtubules into a bipolar array, termed the mitotic spindle. The depolymerization of kinetochore-bound microtubules generates the force required to properly segregate the chromosomes. The work in this thesis analyzes the molecular basis for the function and activity of two key players in microtubule function. First, I investigate the mechanisms by which the Ska1 complex facilitates the continued association of the kinetochore with microtubules, even as the microtubules grow and shrink. I show that Ska1 uses multiple surfaces to interact with diverse tubulin substrates, and each of these surfaces are required for microtubule tip tracking and optimal mitotic progression. Second, I analyze cytoplasmic dynein, a microtubule-based motor that is critically required to maintain spindle bipolarity and execute numerous other cellular processes throughout the cell cycle. The execution of these diverse functions of dynein relies on precise temporal and spatial regulation of dynein activity. Dynein regulation is accomplished in part by the association of adaptor proteins with the dynein complex, including Nde1. Here, I show that Nde1 utilizes distinct intermolecular interactions to regulate different dynein functions. I also identify a previously uncharacterized interaction between Nde1 and the 26S proteasome. Finally, I explore a potential role for post-translational modifications in regulating dynein function. I find that the localization of dynein during mitosis is rapidly altered following the addition of small molecule inhibitors of ubiquitination enzymes. Together, these findings provide new insights into the function and regulation of diverse components of the mitotic machinery.by Julie Kathryn Monda.Ph. D
Organization and regulation of outer kinetochore assembly
No full textThesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 125-138).The kinetochore provides the connection between chromosomes and spindle microtubules. Defining the molecular architecture of the core kinetochore components is critical for understanding the mechanisms by which the kinetochore directs chromosome segregation. The KNL1/Mis12 complex/Ndc80 complex (KMN) network acts as the primary microtubule-binding interface at kinetochores, and provides a platform for recruitment of regulatory proteins. The results in this thesis demonstrate that the CENP-C and CENP-T inner kinetochore receptors form separate scaffolds for KMN network assembly. Initial biochemical results suggested a non-canonical assembly pathway mediated by a direct interaction between CENP-T and the Ndc80 complex. These results were further verified and expanded upon in cells using an ectopic targeting approach to allow careful analysis of the pathways independently of one another. The data presented here demonstrate that in addition to forming two pathways, the CENP-C and CENP-T based assemblies are each constructed uniquely, showing both distinct organization of the KMN components as well as different modes of regulation. Analysis of the CENP-C based assembly pathway has previously defined the canonical architecture of the KMN network as a stable unit that associates with CENP-C via a direct interaction mediated by the Mis12 complex, and the data herein additionally shows that assembly of this pathway is regulated at least in part by Aurora B kinase activity. In contrast, the CENP-T protein forms a direct, CDK-dependent interaction with the Ndc80 complex, and this interaction is required for downstream recruitment of KNL1 and the Mis12 complex, resulting in a novel recruitment pathway for the KMN network. Together these results allow us to generate a new and more detailed molecular model for the assembly of the core structural components of the kinetochore.by Florencia Rago.Ph. D
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
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