106 research outputs found

    Ultrasonic Stimulation of Mouse Skin Reverses the Healing Delays in Diabetes and Aging by Activation of Rac1

    Get PDF
    Chronic skin-healing defects are one of the leading challenges to lifelong well-being, affecting 2–5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed, and driving wound contraction. We discover that mechanical stimulation of the skin with ultrasound can overturn healing defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-dependent signaling and promotes fibroblast migration. Treatment of diabetic and aged mice recruits fibroblasts to the wound bed and reduces healing times by 30%, restoring healing rates to those observed in young, healthy animals. Ultrasound treatment is equally effective in rescuing the healing defects of animals lacking fibronectin receptors, and can be blocked by pharmacological inhibition of the CamKinaseII pathway. Finally, we discover that the migration defects of fibroblasts from human venous leg ulcer patients can be reversed by ultrasound, demonstrating that the approach is applicable to human chronic samples. By demonstrating that this alternative Rac1 pathway can substitute for that normally operating in the skin, we identify future opportunities for management of chronic wounds

    FEL research and development at STFC Daresbury laboratory

    Get PDF
    In this paper we present an overview of current and proposed FEL developments at STFC Daresbury Laboratory in the UK. We discuss progress on the ALICE IR-FEL since first lasing in October 2010, covering the optimisation of the FEL performance, progress on the demonstration of a single shot cross correlation experiment and the results obtained so far with a Scanning Near-Field Optical Microscopy beamline. We discuss a proposal for a 250 MeV single pass FEL test facility named CLARA to be built at Daresbury and dedicated to research for future light source applications. Finally we present a brief overview of other recent research highlights

    Jockeying for position: the construction of masculine identities

    Get PDF
    In this paper we examine the construction of masculine identities within a real-life social situation. Using data from an extensive series of interviews with small groups of sixth-form (17-18-year-old) students attending a UK-based, single-sex independent school, the analysis looks at the action orientation of different constructions of identity. More specifically, it focuses upon how the identity talk of one particular group of students were oriented towards managing their subordinate status within the school. In a number of instances the identity of the `new man' was adopted as a strategy of resistance. However, it was found that the more common strategy involved buying back into values embodied within a more traditional definition of masculinity

    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

    Get PDF
    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

    Botswana

    No full text

    Genetic recombination without sexual reproduction in <i>Aspergillus niger</i>

    No full text
    Roper's technique for the production in filamentous fungi of strains with heterozygous diploid nuclei in their hyphae (Roper, 1952) has been applied successfully to &lt;i&gt;Aspergillus niger&lt;/i&gt;, in which a sexual cycle does not occur. The diploids, heterozygous for known markers, give origin to new strains, most still diploid, homozygous for some or all of the markers and therefore associating or recombining in all possible ways the properties of the two strains from which the diploid was formed. Genetic recombination has thus been achieved in a filamentous fungus without a normal sexual cycle. Imperfect fungi are now open to genetic investigation. Deliberate ‘breeding’ of strains has become a practical proposition in industrial fermentations based on these fungi

    The genetics of <i>Aspergillus nidulans</i>

    No full text
    This discusses the lifecycle, the methods of culture, the isolation of mutants, the formal genetics, the identification of loci, and the diploids and mitotic recombination of Aspergillus nidulans (A. nidulans). It also presents various methods of genetic analysis, such as heterokaryosis, crossing, recombinant selection from random samples of ascosporesa, and perithecium analysis and relative heterothallism. As in most other filamentous fungi in which sexual reproduction occurs, A. nidulans (Eidam) Winter, an ascomycete shows a vegetative cycle side-by-side with a sexual cycle. On germination, an uninucleate haploid vegetative spore (conidium) produces colorless septate hyphae with multinucleate cells. The sexual cycle is concentrated in specialized organs, the fruiting bodies (cleistothecia or perithecia). The biochemical genetics of A. nidulans, though similar to that of Neurospora and Ophiostoma, has revealed interesting differences in detail: e.g., the inability of citrulline to replace ornithine for strains responding to ornithine or arginine; the inability of tryptophan to replace anthranilic acid for certain strains responding to anthranilic acid or nicotinic acid; the competitive inhibition by lysine of exogenous arginine or ornithine, and its sparing effect on exogenous proline; etc
    • …
    corecore