1,722,727 research outputs found
Non-genomic sex steroid actions in the vascular system
No full textSex steroid receptors (SRs) traditionally have been regarded as transcription factors regulating the expression of target genes. However, alternative mechanisms of signal transduction have been identified recently. These actions of sex steroids do not require gene expression or protein synthesis and are independent of the nuclear localization of the receptors. Indeed, some of these actions are elicited by SRs at the plasma membrane. In the recent years significant advances have been made in the characterization of these rapid actions of sex steroids in the vascular system. Prototypical non-genomic actions of sex steroids at this level include the induction of rapid vasodilatation as well as anti-inflammatory and antiatherogenic actions. Ubiquitous signaling pathways traditionally believed to mediate the signals of growth factors or cytokines have been found to be recruited by sex steroid hormones via their receptors. These include tyrosine kinases, c-Src, G proteins, phosphatidylinositol 3-OH kinase/Akt, and mitogen-activated protein kinases. These cascades lead to rapid actions, such as the activation of nitric oxide synthesis, but are also critical for the regulation of the expression of several target genes in the nucleus, indicating a tight integration of the non-genomic and genomic pathways of sex steroid signaling. The understanding of the molecular basis of the non-genomic actions of sex steroids on the vascular system is important, and may become relevant for clinical purposes in the future
Extra-nuclear signaling of estrogen receptors.
No full textEstrogen controls multiple biological functions through binding to estrogen receptors (ERs). Traditionally, ERs have been regarded as transcription factors regulating the expression of target genes. However, growing evidence of rapid estrogen's actions in a number of tissues has been accumulating and alternative mechanisms of signal transduction have been proposed. These so called "extra-nuclear actions" do not require gene expression or protein synthesis and are independent of the nuclear localization of ERs. Indeed, some of these actions are elicited by ERs residing at or near the plasma membrane. Membrane-associated molecules such as ion channels, G proteins, the tyrosine kinase c-Src as well as growth factor receptors are modulated by liganded ERs within the membrane, leading to the activation of downstream cascades such as mitogen-activated protein kinase, phosphatidylinositol 3-OH kinase, protein kinase A, and protein kinase C. These cascades mediate some important rapid actions of estrogen, such as the activation of nitric oxide synthesis or the remodeling of actin cytoskeleton. In addition, these pathways are critical for the regulation of the expression of a number of target proteins implicated in cell proliferation, apoptosis, differentiation, movement, and homeostasis. In this manner, the extra-nuclear pathways are tightly integrated with the genomic pathways to orchestrate the full spectrum of estrogen's biological functions. The recent advancements in the characterization of the molecular basis of the extra-nuclear signaling of estrogen helps to understand the role of estrogen on human cells, and may in future turn out to be of relevance for clinical purposes
Interferon Signaling in Estrogen Receptor-positive Breast Cancer: A Revitalized Topic
No full textCancer immunology is the most rapidly expanding field in cancer research, with the importance of immunity in cancer pathogenesis now well accepted including in the endocrine-related cancers. The immune system plays an essential role in the development of ductal and luminal epithelial differentiation in the mammary gland. Originally identified as evolutionarily conserved antipathogen cytokines, interferons (IFNs) have shown important immune-modulatory and antineoplastic properties when administered to patients with various types of cancer, including breast cancer. Recent studies have drawn attention to the role of tumor- and stromal-infiltrating lymphocytes in dictating therapy response and outcome of breast cancer patients, which, however, is highly dependent on the breast cancer subtype. The emerging role of tumor cell-inherent IFN signaling in the subtype-defined tumor microenvironment could influence therapy response with protumor activities in breast cancer. Here we review evidence with new insights into tumor cell-intrinsic and tumor microenvironment-derived IFN signaling, and the crosstalk of IFN signaling with key signaling pathways in estrogen receptor-positive (ER+) breast cancer. We also discuss clinical implications and opportunities exploiting IFN signaling to treat advanced ER+ breast cancer
The Role of Foreign Technology and Indigenous Innovation in the Emerging Economies: Technological Change and Catching-up
No full textGoing 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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