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Several major conceptual problems regarding specific in vivo functions of the TGF-beta family members remain the key focus of many researchers studying the biology of these secreted signaling molecules. More than 45 members of this family of growth factors have been identified and partially characterized for their molecular roles in numerous processes such as cell proliferation and differentiation, embryonic development, carcinogenesis, immune dysfunction, inflammation and wound healing. The high degree of similarity that exists at the structural level among the isoforms of these growth factors is accompanied by a significant overlap in function, as defined by many in vitro model systems and in vivo systems involving administration of exogenous ligand or of ligand-specific blocking antibodies. The ability to discern the critical functions of these molecules based on patterns of expression has also often been quite difficult. The evolution of more sophisticated functional genomics approaches has been recently instrumental in generating unique perspectives into the mechanisms governing the activity of the members of the TGF-beta family. The studies outlined in this review are significant in that they not only support working hypotheses regarding the activities of TGF-beta generated through extensive in vitro studies but also raise new questions regarding the role of each isoform in numerous processes. With the rapid advances in these approaches to probe activity in a more cell and time-dependent fashion, we will gain valuable insights for designing approaches for targeting the complex cellular pathways mediating their responses and will also help us develop novel therapies to treat disease processes. 相似文献
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Letterio Guglielmo Giacomo Zagami Vincenzo Saggiomo Giulio Catalano Antonia Granata 《Polar Biology》2007,30(6):747-758
The aim of this study was to investigate patterns of abundance, distribution, temporal changes and species composition of
the dominant ice-associated copepods in the spring annual pack ice, platelet ice and water column at Terra Nova Bay, Ross
Sea, during late spring 1997. Ice cores were drilled for temporal and spatial scales. Stephos longipes and Harpacticus furcifer dominated the sea ice meiofauna in terms of numbers in the lower few centimeters of the bottom ice associated with high chlorophyll
a and phaeopigment levels. Nauplii dominated the S. longipes population (91.6%) and occurred in extremely high concentrations. In contrast, copepodids were the dominant stages in H. furcifer. How H. furcifer carries out its entire life cycle and how it differs from ecologically similar species such as Drescheriella glacialis should be examined in more detail. 相似文献
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C Crone J Frokjaer-Jensen JJ Friedman O Christensen 《The Journal of general physiology》1978,71(2):195-220
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The interleukin 2 receptor alpha chain (IL-2Ralpha) is a component of high affinity IL-2 receptors and thus critically regulates T cell growth and other lymphoid functions. Five positive regulatory regions together control lineage-restricted and activation-dependent IL-2Ralpha induction in response to antigen and IL-2. We now show that TGF-beta cooperates with T cell receptor (TCR) signaling to increase IL-2Ralpha gene expression. Moreover, we identify a sixth positive regulatory region that regulates IL-2Ralpha expression in cells treated with anti-CD3 + anti-CD28 as well as TGF-beta and show that this region contains binding sites for Smad3, AP-1, and cAMP-responsive element-binding protein/ATF proteins. The importance of Smad complexes is indicated by impaired IL-2Ralpha induction by TGF-beta in CD4+ T cells from both Smad3-/- and Smad4-/- mice. Thus, we have identified a novel positive regulatory region in the IL-2Ralpha gene that mediates TGF-beta-dependent induction of the gene. These findings have implications related to IL-2Ralpha expression on activated T cells and regulatory T cells. 相似文献
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Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG
Claes Ingmar JJ Segers Marijke E Verhoeven Tine LA Dusselier Michiel Sels Bert F De Keersmaecker Sigrid CJ Vanderleyden Jos Lebeer Sarah 《Microbial cell factories》2012,11(1):1-8