180 research outputs found

    Print & (Pedagogical Issues in Printmaking)

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    This panel addresses how the contemporary printmaker must adapt traditional approaches to making, collaborating, teaching, and networking to an increasingly digital landscape. With creative adaptation a necessity for artists and the medium of printmaking\u27s sustained relevance, panelists will discuss their experiences: transforming traditional journals into digital archives, seeking innovative approaches to portfolio exchanges, pursuing alternative vocations, and readying the next generation of artists for these challenges

    Twist1 Inactivation in Dmp1-Expressing Cells Increases Bone Mass but Does Not Affect the Anabolic Response to Sclerostin Neutralization

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    Wnt signaling plays a major role in bone metabolism. Advances in our understanding of secreted regulators of Wnt have yielded several therapeutic targets to stimulate osteoanabolism—the most promising of which is the Wnt inhibitor sclerostin. Sclerostin antibody recently gained approval for clinical use to treat osteoporosis, but the biology surrounding sclerostin antagonism is still incompletely understood. Numerous factors regulate the efficacy of sclerostin inhibition on bone formation, a process known as self-regulation. In previous communications we reported that the basic helix-loop-helix transcription factor Twist1—a gene know to regulate skeletal development—is highly upregulated among the osteocyte cell population in mice treated with sclerostin antibody. In this communication, we tested the hypothesis that preventing Twist1 upregulation by deletion of Twist1 from late-stage osteoblasts and osteocytes would increase the efficacy of sclerostin antibody treatment, since Twist1 is known to restrain osteoblast activity in many models. Twist1-floxed loss-of-function mice were crossed to the Dmp1-Cre driver to delete Twist1 in Dmp1-expressing cells. Conditional Twist1 deletion was associated with a mild but significant increase in bone mass, as assessed by dual energy x-ray absorptiometry (DXA) and microCT (µCT) for many endpoints in both male and female mice. Biomechanical properties of the femur were not affected by conditional mutation of Twist1. Sclerostin antibody improved all bone properties significantly, regardless of Twist1 status, sex, or endpoint examined. No interactions were detected when Twist1 status and antibody treatment were examined together, suggesting that Twist1 upregulation in the osteocyte population is not an endogenous mechanism that restrains the osteoanabolic effect of sclerostin antibody treatment. In summary, Twist1 inhibition in the late-stage osteoblast/osteocyte increases bone mass but does not affect the anabolic response to sclerostin neutralization

    Efficacy of individualised starting dose (isd) and fixed starting dose (fsd) of niraparib per investigator assessment (ia) in newly diagnosed advanced ovarian cancer (oc) patients

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    Niraparib is a poly(ADP-ribose) polymerase inhibitor approved for maintenance treatment of patients with newly diagnosed or recurrent OC that responded to platinumbased chemotherapy and treatment in heavily-pretreated recurrent OC. Here we report efficacy in patients receiving the FSD and ISD in the PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016)

    Guidelines for reporting of statistics for clinical research in urology

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148242/1/bju14640.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148242/2/bju14640_am.pd

    The mTORC2 Component Rictor Is Required for Load-Induced Bone Formation in Late-Stage Skeletal Cells

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    Bone relies on mechanical cues to build and maintain tissue composition and architecture. Our understanding of bone cell mechanotransduction continues to evolve, with a few key signaling pathways emerging as vital. Wnt/ÎČ‐catenin, for example, is essential for proper anabolic response to mechanical stimulation. One key complex that regulates ÎČ‐catenin activity is the mammalian target of rapamycin complex 2 (mTORc2). mTORc2 is critical for actin cytoskeletal reorganization, an indispensable component in mechanotransduction in certain cell types. In this study, we probed the impact of the mTORc2 signaling pathway in osteocyte mechanotransduction by conditionally deleting the mTORc2 subunit Rictor in Dmp1‐expressing cells of C57BL/6 mice. Conditional deletion of the Rictor was achieved using the Dmp1–Cre driver to recombine Rictor floxed alleles. Rictor mutants exhibited a decrease in skeletal properties, as measured by DXA, ÎŒCT, and mechanical testing, compared with Cre‐negative floxed littermate controls. in vivo axial tibia loading conducted in adult mice revealed a deficiency in the osteogenic response to loading among Rictor mutants. Histological measurements of osteocyte morphology indicated fewer, shorter cell processes in Rictor mutants, which might explain the compromised response to mechanical stimulation. In summary, inhibition of the mTORc2 pathway in late osteoblasts/osteocytes leads to decreased bone mass and mechanically induced bone formation

    How can an understanding of plant-pollinator interactions contribute to global food security?

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    Pollination of crops by animals is an essential part of global food production, but evidence suggests that wild pollinator populations may be declining while a number of problems are besetting managed honey bee colonies. Animal-pollinated crops grown today, bred in an environment where pollination was less likely to limit fruit set, are often suboptimal in attracting and sustaining their pollinator populations. Research into plant-pollinator interactions is often conducted in a curiosity-driven, ecological framework, but may inform breeding and biotechnological approaches to enhance pollinator attraction and crop yield. In this article we review key topics in current plant-pollinator research that have potential roles in future crop breeding for enhanced global food security
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