1,720,960 research outputs found
A NOVEL MICRO-RNA FAMILY AS MOLECULAR DETERMINANT OF MAMMARY STEM CELLS
Get PDFA novel microRNA family as molecular determinant in mammary stem cells
MicroRNAs (miRNAs) are an evolutionarily conserved class of small (18-22 nucleotides) noncoding RNAs involved in the regulation of a variety of cellular and developmental processes. MiRNAs have recently emerged as key regulators of transcriptional programs that control self-renewal and the cell-fate of stem cells (SCs). In the breast compartment, forced expression of some miRNAs (e.g. miR-200, let-7 and miR-93) was shown to inhibit normal and/or cancer SCs by silencing self-renewal determinants. In fact, these miRNAs are poorly or not expressed in the SC compartment, and their stem-inhibiting function is mainly achieved through the induction of differentiation.
The aim of this project is to identify miRNAs specifically expressed in mammary SCs isolated from normal and cancer samples that could act as markers and/or as regulators of stem cell biology. We will also evaluate their potential as novel therapeutic targets in breast cancer.
Using an innovative technique developed in our lab for the isolation of quasi-pure SCs/CSCs, we identified a miRNA family as being highly enriched in the SC compartment, in both primary normal and tumor samples. Endogenous levels of miRNAs of this family can stratify distinct sub-populations with different SC abilities, and in human cancer high miRNA levels correlate with a basal tumor subtype and with an elevated CSC content. Furthermore, depletion of these miRNAs by a synthetic sponge impair self-renewal of SCs/CSCs, as measured by a serial mammosphere propagation assay in human cancer cell lines and in mouse primary epithelial cells. In vivo, miRNA loss reduced the frequency of tumor formation, as well as the mean tumor volume and the frequency of CSCs measured with either an established human basal-like cancer cell line or human patient-derived xenografts (PDXs). To determine the molecular mechanisms underlying the regulation of SCs/CSCs behavior, we employed an unbiased approach assessing the effects of miRNA loss on global gene expression profile, coupled with the prediction of miRNA targets involved in stem cell biology. We identified 91 stem cell genes that are putatively targeted by this miRNA family, belonging to pathways critically involved in the regulation or in the mainteinance of stem cell traits.
In conclusion, our results suggest that this SC-specific miRNA family could potentially be used as novel therapeutic targets for breast cancer treatment. This study also provides insights into the mechanisms that sustain CSCs growth in the breast, involving complex molecular circuits of coding as well as noncoding RNAs
The role of non-coding RNAs in the regulation of stem cells and progenitors in the normal mammary gland and in breast tumors
Get PDFThe outlook on stem cell biology is shifting from a rigid hierarchical to a more flexible model in which the identity and the behavior of adult stem cells (SCs), far from being fixed, are determined by the dynamic integration of cell autonomous and non-autonomous mechanisms. Within this framework, the recent discovery of thousands of non-coding RNAs (ncRNAs) with regulatory function is redefining the landscape of transcriptome regulation, highlighting the interplay of epigenetic, transcriptional and post-transcriptional mechanisms in the specification of cell fate and in the regulation of developmental processes. Furthermore, the expression of ncRNAs is often tissue- or even cell type-specific, emphasizing their involvement in defining space, time and developmental stages in gene regulation. Such a role of ncRNAs has been investigated in embryonic and induced pluripotent stem cells, and in numerous types of adult SCs and progenitors, including those of the breast, which will be the topic of this review. We will focus on ncRNAs with an important role in breast cancer, in particular in mammary cancer stem cells and progenitors, and highlight the ncRNA-based circuitries whose subversion alters a number of the epigenetic, transcriptional and post-transcriptional events that control "stemness" in the physiological setting
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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