74 research outputs found

    TIEG1/KLF10 Modulates Runx2 Expression and Activity in Osteoblasts

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    Deletion of TIEG1/KLF10 in mice results in a gender specific osteopenic skeletal phenotype with significant defects in both cortical and trabecular bone, which are observed only in female animals. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display reduced expression levels of multiple bone related genes, including Runx2, and exhibit significant delays in their mineralization rates relative to wildtype controls. These data suggest that TIEG1 plays an important role in regulating Runx2 expression in bone and that decreased Runx2 expression in TIEG1 KO mice is in part responsible for the observed osteopenic phenotype. In this manuscript, data is presented demonstrating that over-expression of TIEG1 results in increased expression of Runx2 while repression of TIEG1 results in suppression of Runx2. Transient transfection and chromatin immunoprecipitation assays reveal that TIEG1 directly binds to and activates the Runx2 promoter. The zinc finger containing domain of TIEG1 is necessary for this regulation supporting that activation occurs through direct DNA binding. A role for the ubiquitin/proteasome pathway in fine tuning the regulation of Runx2 expression by TIEG1 is also implicated in this study. Additionally, the regulation of Runx2 expression by cytokines such as TGFβ1 and BMP2 is shown to be inhibited in the absence of TIEG1. Co-immunoprecipitation and co-localization assays indicate that TIEG1 protein associates with Runx2 protein resulting in co-activation of Runx2 transcriptional activity. Lastly, Runx2 adenoviral infection of TIEG1 KO calvarial osteoblasts leads to increased expression of Runx2 and enhancement of their ability to differentiate and mineralize in culture. Taken together, these data implicate an important role for TIEG1 in regulating the expression and activity of Runx2 in osteoblasts and suggest that decreased expression of Runx2 in TIEG1 KO mice contributes to the observed osteopenic bone phenotype

    Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

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    BACKGROUND: Insulin-like growth factor-I (IGF-I) plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH), or both (GH+IGF-I) would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs), while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments. RESULTS: Tissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to) values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF-I. CONCLUSION: These results support two of our hypotheses that systemic administration of IGF-I or GH+IGF-I improve healing in collagenous tissue. Systemic administration of IGF-I improves healing in collagenous extracellular matrices from loaded and unloaded tissues. Growth hormone alone did not result in any significant improvement contrary to our hypothesis, while GH + IGF-I produced remarkable improvement in hindlimb unloaded animals

    Social Media, Gender and the Mediatisation of War: Exploring the German Armed Forces’ Visual Representation of the Afghanistan Operation on Facebook

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    Studies on the mediatisation of war point to attempts of governments to regulate the visual perspective of their involvements in armed conflict – the most notable example being the practice of ‘embedded reporting’ in Iraq and Afghanistan. This paper focuses on a different strategy of visual meaning-making, namely, the publication of images on social media by armed forces themselves. Specifically, we argue that the mediatisation of war literature could profit from an increased engagement with feminist research, both within Critical Security/Critical Military Studies and within Science and Technology Studies that highlight the close connection between masculinity, technology and control. The article examines the German military mission in Afghanistan as represented on the German armed forces’ official Facebook page. Germany constitutes an interesting, and largely neglected, case for the growing literature on the mediatisation of war: its strong antimilitarist political culture makes the representation of war particularly delicate. The paper examines specific representational patterns of Germany’s involvement in Afghanistan and discusses the implications which arise from what is placed inside the frame of visibility and what remains out of its view

    A production scheduling system for a hybrid flow shop--a case study

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    This paper presents a production scheduling system for photographic film manufacturing industries. The scheduling system considers a hybrid flow shop, which consists of two manufacturing stages: first, the slitting of the film bulk-roll, and second, the interleaving and wrapping of the slitted sheets. In this study, several hundred final productions are produced from the film bulk-roll based on the actual demands for final products. This production scheduling system was designed as a decision support system by combining computer capability with production management. The selected performance criteria for making a schedule were ratio of setup time to processing time, work-in-process level ratio of attainable production quantity of final products to the planned production quantity. The system designed for this study showed more favourable results than the conventional system.production scheduling system hybrid flow shop

    A Systematic Study of the Thermal and Nonthermal Emission in the Supernova Remnant RCW 86 with Suzaku

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    Diffusive shock acceleration by the shockwaves in supernova remnants (SNRs) is widely accepted as the dominant source for Galactic cosmic rays. However, it is unknown what determines the maximum energy of accelerated particles. The surrounding environment could be one of the key parameters. The SNR RCW 86 shows both thermal and non-thermal X-ray emission with different spatial morphologies. These emission originate from the shock-heated plasma and accelerated electrons respectively, and their intensities reflect their density distributions. Thus, the remnant provides a suitable laboratory to test possible association between the acceleration efficiency and the environment. In this paper, we present results of spatially resolved spectroscopy of the entire remnant with Suzaku. The spacially-resolved spectra are well reproduced with a combination of a power-law for synchrotron emission and a two-component optically thin thermal plasma, corresponding to the shocked interstellar medium (ISM) with kT of 0.3-0.6 keV and Fe-dominated ejecta. It is discovered that the photon index of the nonthermal component becomes smaller with decreasing the emission measure of the shocked ISM, where the shock speed has remained high. This result implies that the maximum energy of accelerated electrons in RCW 86 is higher in the low-density and higher shock speed regions.Comment: 14 pages, 15 figures, ApJ accepte
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