1,720,984 research outputs found
A novel Granule Cell Progenitors culture method as a new tool for investigating Hedgehog and other pathways relevant to cerebellar development and tumorigenesis
Get PDFThe Hedgehog (Hh) signaling is an essential pathway involved in development and cancer. Via the interaction with the 12-span transmembrane receptor Ptch, Hh ligands (Sonic, Desert and Indian Hh) release the activity of the 7-span membrane protein Smo. Yet uncompletely characterized molecular mechanisms, involving postranslational modifications of Smo and its shuttling within the primary cilium, translate the signal into the activation of the Gli family of transcription factors. The interplay between the three Gli members (Gil1, 2 and 3) regulates Hh-dependent transcription of a number of gene targets, many of which are master regulators of cell proliferation, such as N-Myc and Cyclin-D.
Hh pathway plays a pivotal role in cerebellar postnatal development, where it appears the main promoter of granule cell progenitors (GCPs) expansion, which in the mouse occurs between postnatal day (P)1 and P14, the time frame in which Hh signalling in the cerebellum raises up to its maximum (P7) and declines. By P14-P21 cerebellar maturation is completed. Silencing of Hh activity at the proper developmental time is molecularly regulated at multiple levels, some of which are still partially obscure, and appears to be essential to prevent transformation of GCPs into medulloblastoma.
Despite intense investigations, several aspects of Hh pathway activation and deactivation are not completely understood or conflicting interpretations exist. This is at least partially due to lack of appropriate models for the study of this pathway, in vitro. Indeed, Hh pathway gets quickly repressed in cell cultures, both in normal or cancer cells. Only transient cultures of freshly explanted primary granule cells (GC) allows Hh pathway investigation in a “naive” context, but only for few days.
Since this has long represented a big limitation in the field, we have recently developed a new procedure for GCPs colture, which overcome the limits of currently available models (transients cell cultures among other problems). Under the hypothesis that eliminating Hh-inhibiting growth factors and under the direct stimulation of Hh signal in the cell colture medium, GCs could be grown as neurosphere, we indeed generated a new primary model of GCPs with high and
continuosly active Hh signalling.
Under defined concentrations of the SMO agonist SAG, cells explanted from P7 cerebelli can be undefinetely grown in colture as neurospheres. These neurospheres demonstrate complete activation overtime of the main effectors of Hh pathway Gli1 and N-Myc. They further show self-renewal capability in vitro, and constitutive expression of stemness genes, such as POU3f2, POU5f1, NANOG, and SOX2. These cultures do not get transformed during long periods in culture, as suggested by their continuous dependence on SAG.
SAG-dependent neurospheres express ZIC1, ATOH1 and NESTIN, which define their origin as GCPs. Consistently, these cells may be induced to differentiate into a homogeneous population of mature GC, expressing specifics markers such as TUBB3 and GABRA 6. Moreover, SAG-dependent cultures cannot be generated by the subventricular zone, but only from the mouse cerebellar explants taken at P1-P7.
Primary and continuously growing neurospheres of the same type can be generated by GC explanted from Ptch KO animal, even without SAG, further suggesting that, in the absence of specific Hh inhibitory factors, constitutive Hh activation is the only element required for their growth and survival.
Overall, these data suggest that using culture conditions that mimic the appropriate biological signalling, allowed the isolation a of transient amplifying GCP population in vitro, which is able to propagate in culture for undefined periods of time. This model represents a novel and important tool to study issues related to physiological and pathological aspects of Hh-dependent GCPs growth and differentiation in a cell autonomous environment.
By generating GC neurospheres from different mouse models we are now addressing important issues related to Hh signaling, but also to other pathways. In example, we have shown that the SmoM2 (Trp535Leu) mutation expressed in the transgenic SMOA1 medulloblastoma mouse model does not imply a full and constitutive activation of the SMO receptor, as commonly thought. Moreover, we have used these cultures to show that the knock-out of the DNA repair gene NBS1 specifically impairs Hh-dependent GCPs growth
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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