1,721,058 research outputs found

    The retinoblastoma gene is involved in multiple aspects of stem cell biology

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    Genetic programs controlling self-renewal and multipotentiality of stem cells have overlapping pathways with cell cycle regulation. Components of cell cycle machinery can play a key role in regulating stem cell self-renewal, proliferation, differentiation and aging. Among the negative regulators of cell cycle progression, the RB family members play a prominent role in controlling several aspects of stem cell biology. Stem cells contribute to tissue homeostasis and must have molecular mechanisms that prevent senescence and hold 'stemness'. RB can induce senescence-associated changes in gene expression and its activity is downregulated in stem cells to preserve self-renewal. Several reports evidenced that RB could play a role in lineage specification of several types of stem cells. RB has a role in myogenesis as well as in cardiogenesis. These effects are not only related to its role in suppressing E2F-responsive genes but also to its ability to modulate the activity of tissue-specific transcription factors. RB is also involved in adipogenesis through a strict control of lineage commitment and differentiation of adipocytes as well in determining the switch between brown and white adipocytes. Also, hematopoietic progenitor cells utilize the RB pathway to modulate cell commitment and differentiation. In this review, we will also discuss the role of the other two RB family members: Rb2/p130 and p107 showing that they have both specific and overlapping functions with RB gene. © 2006 Nature Publishing Group All rights reserved

    Stem cells and brain cancer

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    An increasing body of research is showing that cancers might contain their own stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a deregulated cellular self-renewal capacity. This raises the possibility that some features of tumor cells may be due to cancer stem cells. Stem cell-like cancer cells were isolated from several solid tumors. Now, evidence has shown that brain cancers, such as glioblastomas, medulloblastomas and astrocytomas, also contain cells that may be multipotent neural stem cell-like cells. In this review, we discuss the results of these studies, along with the molecular pathways that could be involved in cancer stem cell physiopathology

    Partial silencing of methyl cytosine protein binding 2 (MECP2) in mesenchymal stem cells induces senescence with an increase in damaged DNA

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    DNA methylation is an epigenetic modification that occurs almost exclusively on CpG dinucleotides. MECP2 is a member of a family of proteins that preferentially bind to methylated CpGs. We analyzed the contribution of MECP2 to the physiology of mesenchymal stem cells (MSCs). Partial silencing of MECP2 in human MSCs induced a significant reduction of S-phase cells, along with an increase in G(1) cells. These changes were accompanied by a reduction of apoptosis, the triggering of senescence, a decrease in telomerase activity, and the down-regulation of genes involved in maintaining stem cell properties. Senescence appeared to rely on impairment of DNA damage repair and seemed to occur through RB- and P53-related pathways. The effects of MECP2 silencing could be related to the modification of the DNA methylation status. Our results indicate that the silencing of MECP2 induces an increase in methylated cytosines in the genome. Nevertheless, MECP2 partial silencing did not change the methylation of promoters, whose expression is affected by MECP2 down-regulation

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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
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