1,721,072 research outputs found
In Vivo Silencing/Overexpression of lncRNAs by CRISPR/Cas System
No full textLong noncoding RNAs (lncRNAs) are implicated in several biological processes and it has been observed that their expression is altered in several diseases. The generation of animal models where selective silencing or overexpression of lncRNAs can be attained is crucial for their biological characterization, since it offers the opportunity to analyze their function at the tissue specific or organismal level. CRISPR/Cas technology is a newly developed tool that allows to easily manipulate the mouse genome, in turn allowing to discover lncRNAs functions in an in vivo context. Here, we provide an overview of how CRISPR/Cas technology can be used to generate transgenic mouse models in which lncRNAs can be studied
An Immunocompetent Environment Unravels the Proto-Oncogenic Role of miR-22
No full textMiR-22 was first identified as a proto-oncogenic microRNA (miRNA) due to its ability to post-transcriptionally suppress the expression of the potent PTEN (Phosphatase And Tensin Homolog) tumor suppressor gene. miR-22 tumorigenic role in cancer was subsequently supported by its ability to positively trigger lipogenesis, anabolic metabolism, and epithelial-mesenchymal transition (EMT) towards the metastatic spread. However, during the following years, the picture was complicated by the identification of targets that support a tumor-suppressive role in certain tissues or cell types. Indeed, many papers have been published where in vitro cellular assays and in vivo immunodeficient or immunosuppressed xenograft models are used. However, here we show that all the studies performed in vivo, in immunocompetent transgenic and knock-out animal models, unanimously support a proto-oncogenic role for miR-22. Since miR-22 is actively secreted from and readily exchanged between normal and tumoral cells, a functional immune dimension at play could well represent the divider that allows reconciling these contradictory findings. In addition to a critical review of this vast literature, here we provide further proof of the oncogenic role of miR-22 through the analysis of its genomic locus vis a vis the genetic landscape of human cancer
Nucleophosmin and cancer
No full textNPM1 is a crucial gene to consider in the context of the genetics and biology of cancer. NPM1 is frequently overexpressed, mutated, rearranged and deleted in human cancer. Traditionally regarded as a tumour marker and a putative proto-oncogene, it has now also been attributed with tumour-suppressor functions. Therefore, NPM can contribute to oncogenesis through many mechanisms. The aim of this review is to analyse the role of NPM in cancer, and examine how deregulated NPM activity (either gain or loss of function) can contribute to tumorigenesis
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
PTENP1 is a ceRNA for PTEN: It's CRISPR clear
Full text linkHere we apply state-of-the-art CRISPR technologies to study the impact that PTENP1 pseudogene transcript has on the expression levels of its parental gene PTEN, and hence on the output of AKT signaling in cancer. Our data expand the repertoire of approaches that can be used to dissect competing endogenous RNA (ceRNA)-based interactions, while providing further experimental evidence in support of the very first one that we discovered
NGF-promoted axon growth and target innervation requires GITRL-GITR signaling
No full textNerve growth factor (NGF) has an important role in regulating sympathetic neuron survival and target field innervation during development. Here we show that glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), a member of the TNF superfamily, and its ligand (GITRL) are co-expressed in mouse sympathetic neurons when their axons are innervating their targets under the influence of target-derived NGF. In culture, GITRL enhanced NGF-promoted neurite growth from neonatal sympathetic neurons, and preventing GITR-GITRL interaction in these neurons or knocking down GITR inhibited NGF-promoted neurite growth without affecting neuronal survival. Tnfrsf18(-/-) (Gitr) neonates have reduced sympathetic innervation density in vivo compared with Gitr(+/+) littermates. GITR activation is required for the phosphorylation of extracellular signal-regulated kinases 1 and 2 by NGF that is necessary for neurite growth. Our results reveal a previously unknown signaling loop in developing sympathetic neurons that is crucial for NGF-dependent axon growth and target innervation
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
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