1,721,004 research outputs found
EXPLORING THE ROLE OF WNT10B AS LEUKEMIA DRIVER IN ZEBRAFISH MODEL
Full text linkABSTRACT
Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by a misregulation in the differentiation program of myeloid progenitor cells that proliferate abnormally and arrest in their maturation. In the effort to reveal the mechanism that confers self-renewal potential to Leukemia Stem Cells (LSCs), Wnt pathway came out as a candidate. The Wnt pathway has a central role in the hematopoiesis regulating the hematopoietic stem cells (HSCs) self-renewal. A recent study showed an increase of WNT proteins (i.e. WNT10B) expression and release within the microenvironment in both leukemic blasts and stromal-like cells of AML patients, indicating its possible autocrine/paracrine involvement in the bone marrow microenvironment, and suggesting that the regenerative WNT signaling is a stem cell-associated function altered in AML stem cell fraction. The aim of this work is to elucidate the role of WNT10B in AML generating an animal model in which this signaling is disregulated.
The striking similarities of zebrafish and human hematopoiesis make this fish an excellent model for elucidating physiologic and pathological mechanisms. Furthermore, various hematopoietic zebrafish mutants, mimicking the human hematopoietic system diseases, have been generated. wnt10b was transiently upregulated in zebrafish embryos and effects of such misregulation on embryonic hematopoiesis were analyzed. In-situ hybridization assays, performed using myeloid and HSCs markers (pu.1 and scl, respectively), and in vivo observation of transgenic fish lines expressing fluorescent proteins in erythroid progenitors and mature neutrophils - Tg(gata1:dsRed) and Tg(mpx:EGFP) - demonstrated an abnormal accumulation of HSCs, myeloid and erythroid progenitors in the embryo hematopoietic tissue, at the expense of more differentiated cells. Moreover, wnt10b overexpression affects the migration of myeloid cells in the ALM (Anterior Lateral Mesoderm). Taken together, these results support the notion of an involvement of wnt10b in vertebrate hematopoiesis.
A plasmid construct with zebrafish wnt10b under the control of runx1 (a pivotal gene in definitive hematopoiesis) promoter and flanked by trasposase-responsive elements has been generated; injection of this plasmid in zebrafish embryos together with trasposase mRNA will lead to the generation of a transgenic line in which wnt10b expression can be induced only in definitive HSCs. Future plans include the temporal control of the transgene expression through the insertion in the plasmid of a lox-P cassette flanking a STOP signal and the outcross of the resulting transgenic line with a line expressing Cre recombinase under the control of hsp70 (heat-shock protein) promoter. This model will provide the chance to better understand the Wnt-mediated early mechanisms that lead to leukemia development
Use of IR-spectroscopy and diffraction to discriminate between natural, synthetic and treated turquoise, and its imitations
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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
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