1,720,955 research outputs found
Dissecting the function of NuMA in cleavage furrow formation and chromatin decondensation at the mitotic exit in animal cells
No full textIn animal cells, the duplicated genetic material is aligned on a microtubule-based structure known as the mitotic spindle during mitosis. At the mitotic exit, the mitotic spindle elongates, and the sister chromatids get separated. The separation of sister chromatids is followed by the cleavage furrow formation and its ingression, which eventually partition the cytoplasmic constituents and genetic material into newly formed daughter cells. How the chromosome separation is coordinated with cleavage furrow formation is incompletely understood. Also, when animal cells enter mitosis, the chromatin gets highly condensed, and the transcription is chiefly paused. However, when cells exit mitosis, the chromatin should get decondensed in a tightly regulated manner to ensure proper landscaping of chromosome territories, which makes it competent enough for DNA-based processes like replication and transcription. The accurate functioning of these processes is critical for the development and for stem cell divisions. In this study, we have linked the function of an evolutionarily conserved protein, nuclear mitotic apparatus (NuMA), in cleavage furrow formation and chromatin decondensation at the mitotic exit. In the first part of my thesis, we have tried to characterize the function of chromatin-localized NuMA in regulating chromatin decondensation. In the second part, we have attempted to provide insight into how spatial localization of NuMA at the plasma membrane coordinates chromosome separation with cleavage furrow formation.
1). NuMA regulates chromatin decondensation at the mitotic exit and nuclear shape in interphase cells
NuMA is a highly abundant (~10^6 copies) protein of interphase nuclei. Few studies hint that nuclear NuMA may have a role in chromatin organization, and it is hypothesized to be a part of the nuclear structural framework. In this regard, the loss of NuMA's function based on antibody-based microinjections was associated with nuclear shape defects. However, since the depletion of NuMA is linked with multiple mitotic abnormalities, it remained unclear whether the nuclear shape defects seen upon NuMA depletion is an indirect effect due to impairment of NuMA's mitotic function or a direct outcome of the absence of NuMA in the nucleus. Further, whether NuMA is bound to chromatin in the nucleus was also unknown. Even if NuMA is bound to chromatin, what mechanisms ensure its release upon mitotic entry was unknown. In this work, by utilizing fluorescence recovery after photobleaching (FRAP) and biochemical analysis, we report that NuMA is transiently bound to chromatin in the nucleus. We show that NuMA, which is bound to DNA, is released in late prophase upon nuclear envelope breakdown (NEBD) by the action of Cdk1-CyclinB kinase. Importantly, we identify evolutionarily conserved sequences rich in basic amino acids, arginine, and lysine, at the C-terminus of NuMA that aid in its direct interaction with DNA. In the absence of such interaction, NuMA becomes significantly mobile in the nucleus. Notably, the expression of the DNA-binding deficient mutant of NuMA delays chromatin decondensation at the mitotic exit. Furthermore, we discovered that DNA binding deficient NuMA polymerizes into high-order structures such as fibrillar networks, which perturbs nuclear shape. The DNA-binding property of NuMA prevents the formation of these higher-order structures and thus helps in maintaining the proper nuclear architecture. Overall, this study links the chromatin binding ability of NuMA with the proper chromatin decondensation at mitotic exit and maintenance of nuclear shape in interphase, independent of its mitotic role.
2). Polarized membrane distribution of NuMA/dynein and Ect2/Cyk4/Mklp1 regulate cleavage furrow formation
Animal cells partition their genetic material and cellular constituents through cytokinesis. The initiation of cytokinesis is regulated by the activation of small GTPase RhoA that helps in myosin II activation and actin polymerization at the equatorial membrane, resulting in cleavage furrow formation. RhoA is spatiotemporally regulated by a heterotetrameric complex known as centralspindlin consisting of a dimer of kinesin-6 member Mklp1 and a dimer of RhoGAP Cyk4. The centralspindlin complex localizes at the spindle midzone and promotes the localization of its downstream effectors RhoGEF Ect2 which directly activates RhoA and regulates cytokinesis. However, how a precise RhoA zone at the equatorial membrane is established and maintained remained unclear.
In anaphase, the mitotic protein NuMA is enriched at the polar membrane via its direct interaction with membrane phospholipids, PtIns(4)P and PtIns(4,5)P2 and is vital for proper spindle elongation by cortically anchoring the dynein/dynactin complex. However, despite the presence of PtIns(4)P and PtIns(4,5)P2 throughout the membrane, the NuMA/dynein complexes are restricted to the polar membrane and are excluded from the equatorial membrane, which is mutually exclusively occupied by RhoA. The mechanism of equatorial membrane exclusion of NuMA/dynein complex and its biological relevance remained unknown. In this work, we uncovered that Ect2, Cyk4, and Mklp1 are critical in restricting NuMA/dynein to the polar cortical region. In the absence of Ect2, Cyk4, or Mklp1, NuMA/dynein complex occupies the equatorial cortex, which impacts proper spindle elongation. Further, we show that Ect2 is in complex with Cyk4 and Mklp1 in anaphase cells. We establish that the membrane localization, but not the spindle midzone localization of the Ect2/Cyk4/Mklp1 complex, is critical for NuMA/dynein exclusion and, thus, for proper spindle elongation. Conversely, we show that polar membrane localization of the NuMA/dynein complex confines RhoA to a narrow zone at the equatorial membrane, which ensures cleavage furrow formation and cytokinesis. Overall our work provides insight into the mechanism that restricts NuMA/dynein and Ect2/Cyk4/Mklp1 to mutually exclusive membrane surfaces, which ensures proper chromatin segregation and cleavage furrow formation in animal cells. This coordination is critical for an error-free cell division program
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
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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