722 research outputs found

    Hijacking ZIP codes: posttanscriptional regulation of CCN2 by nucleophosmin

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    CCN2 (connective tissue growth factor [CTGF]/hypertrophic chondrocyte-specific gene product 24 [Hcs24]) is regulated at the transcriptional and posttranscriptional level. For example, an element in the its 3′ untranslated region (3′-UTR) of the CCN2 mRNA controls message stability in chondrocytes. In a recent study, Mukudai et al. (Mol Cell Biol 28:6134-6147, 2008) purified and identified a trans-factor protein binding to the minimal repressive cis element in the 3′-UTR of ccn2 mRNA and identify this protein as the multifunctional nucleolar phosphoprotein nucleophosmin (NPM) This commentary summarizes these observations

    TAK1 Is Required for Dermal Wound Healing and Homeostasis

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    Dermal connective tissue is a supportive structure required for skin’s barrier function; dysregulated dermal homeostasis results in chronic wounds and fibrotic diseases. The multifunctional cytokine transforming growth factor (TGF) β promotes connective tissue deposition, repair, and fibrosis. TGF-β acts through well-defined canonical pathways; however, the non-canonical pathways through which TGF-β selectively promotes connective tissue deposition are unclear. In dermal fibroblasts, we show that inhibition of the non-canonical TGF-β-activated kinase 1 (TAK1) selectively reduced the ability of TGF-β to induce expression of a cohort of wound healing genes, such as collagens, CCN2, TGF-β1, and IL-6. Fibroblast-specific TAK1-knockout mice showed impaired cutaneous tissue repair and decreased collagen deposition, α-smooth muscle actin and CCN2 expression, proliferating cell nuclear antigen staining, and c-Jun N-terminal kinase and p38, but not Smad3, phosphorylation. TAK1-deficient fibroblasts showed reduced cell proliferation, migration, cell attachment/spreading, and contraction of a floating collagen gel matrix. TAK1-deficient mice also showed progressively reduced skin thickness and collagen deposition. Thus, TAK1 is essential for connective tissue deposition in the dermis

    Therapeutic Vascular Compliance Change May Cause Significant Variation in Coronary Perfusion: A Numerical Study

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    In some pathological conditions like aortic stiffening and calcific aortic stenosis (CAS), the microstructure of the aortic root and the aortic valve leaflets are altered in response to stress resulting in changes in tissue thickness, stiffness, or both. This aortic stiffening and CAS are thought to affect coronary blood flow. The goal of the present paper was to include the flow in the coronary ostia in the previous fluid structure interaction model we have developed and to analyze the effect of diseased tissues (aortic root stiffening and CAS) on coronary perfusion. Results revealed a significant impact on the coronary perfusion due to a moderate increase in the aortic wall stiffness and CAS (increase of the aortic valve leaflets thickness). A marked drop of coronary peak velocity occurred when the values of leaflet thickness and aortic wall stiffness were above a certain threshold, corresponding to a threefold of their normal value. Consequently, mild and prophylactic treatments such as smoking cessation, exercise, or diet, which have been proven to increase the aortic compliance, may significantly improve the coronary perfusion

    A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells

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    Members of the CCN family of matricellular signaling regulators promote cell adhesion through integrins and heparan sulfate-containing proteoglycans. A paradox of the CCN field is that, depending on the set of circumstances examined, individual CCN molecules can have quite different, and often opposing, effects. In a recent report, Franzen and colleagues (Mol Cancer Res. 7:1045–1055, 2009) show using siRNA knockdown that CCN1 (cyr61) is essential for the proliferation of prostate cancer cells. Intriguingly, on the other hand, CCN1 also enhances TRAIL-induced apoptosis. Thus the utility of anti-CCN1 therapy in cancer needs to be carefully considered in light of these divergent results. The significance of this paper is discussed

    In vitro comparison of Günther Tulip and Celect filters. Testing filtering efficiency and pressure drop

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    In this study, the trapping ability of the Günther Tulip and Celect inferior vena cava filters was evaluated. Thrombus capture rates of the filters were tested in vitro in horizontal position with thrombus diameters of 3 and 6. mm and tube diameter of 19. mm. The filters were tested in centered and tilted positions. Sets of 30 clots were injected into the model and the same process was repeated 20 times for each different condition simulated. Pressure drop experienced along the system was also measured and the percentage of clots captured was recorded. The Günther Tulip filter showed superiority in all cases, trapping almost 100% of 6. mm clots both in an eccentric and tilted position and trapping 81.7% of the 3. mm clots in a centered position and 69.3% in a maximum tilted position. The efficiency of all filters tested decreased as the size of the embolus decreased and as the filter was tilted. The injection of 6 clots raised the pressure drop to 4.1. mmHg, which is a reasonable value that does not cause the obstruction of blood flow through the system

    Improving the professional knowledge base for education: Using knowledge management (KM) and Web 2.0 tools

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    Improving education systems is an elusive goal. Despite considerable investment, international studies such as the OECD Teaching and Learning International Survey (TALIS) project and the McKinsey Report How the world’s best performing schools come out on top indicate that improving teacher quality is more important than increased financial investment. Both reports challenge governments, academics and practitioners to adopt new ways of sharing and building knowledge. This paper makes the case for national education systems to adopt tried and tested knowledge management and web 2.0 tools used by other sectors and highlights the neglected potential of teacher educators as agents for improvement

    The Alaska Council On Science and Technology: A Preliminary Assessment

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    The State of Alask

    Alaska's North Slope Borough: Oil, Money and Eskimo Self-Government

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    The State of Alask

    Challenges in the Search for Perchlorate and Other Hydrated Minerals With 2.1-μm Absorptions on Mars

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    A previously unidentified artifact has been found in Compact Reconnaissance Imaging Spectrometer for Mars targeted I/F data. It exists in a small fraction (<0.05%) of pixels within 90% of images investigated and occurs in regions of high spectral/spatial variance. This artifact mimics real mineral absorptions in width and depth and occurs most often at 1.9 and 2.1 μm, thus interfering in the search for some mineral phases, including alunite, kieserite, serpentine, and perchlorate. A filtering step in the data processing pipeline, between radiance and I/F versions of the data, convolves narrow artifacts (“spikes”) with real atmospheric absorptions in these wavelength regions to create spurious absorption-like features. The majority of previous orbital detections of alunite, kieserite, and serpentine we investigated can be confirmed using radiance and raw data, but few to none of the perchlorate detections reported in published literature remain robust over the 1.0- to 2.65-μm wavelength range
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