Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development

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PCBs Exert an Estrogenic Effect through Repression of the Wnt7a Signaling Pathway in the Female Reproductive Tract

Polychlorinated biphenyls (PCBs) have been proposed to have a weak estrogenic activity and therefore pose a risk as potential environmental endocrine disruptors to the perinatal development of the female reproductive tract. Perinatal exposure to high concentrations of the potent synthetic estrogen diethylstilbestrol (DES) induces abnormal development of the female reproductive tract via a mechanism that acts through the down-regulation of Wnt7a (wingless-type MMTV integration site family, member 7A). To test the hypothesis that PCBs act as weak estrogens, we injected neonatal mice with a commercial PCB mixture (Aroclor 1254) or with low levels of DES and measured effects of exposure on Wnt7a expression and uterine morphology. We report here that neonatal PCB or low-level DES exposure resulted in the down-regulation of Wnt7a expression. In addition, both PCB and low-level DES exposure induced changes in the uterine myometrium and gland formation. These data reveal that weak estrogens such as the PCBs act through a Wnt7a-dependent pathway and suggest that Wnt7a regulation is a sensitive biomarker for testing weak estrogenic candidate compounds. The morphologic changes that were elicited by PCBs and DES were different immediately after exposure, suggesting that Wnt7a-independent pathways are also activated by one or both of these compounds. Although Wnt7a down-regulation is transient after estrogenic exposure, subsequent morphologic changes became more pronounced during postnatal and adult life, suggesting that the female reproductive tract is permanently reprogrammed after exposure even to weak estrogenic compounds. In addition, Wnt7a heterozygous mice were more sensitive to PCB exposure, revealing an important genetic predisposition to risks of environmental endocrine disruptors

A very conscientious brand: A case study of the BBC's current affairs series Panorama

The reputation of British current affairs and documentary series such as the BBC's Panorama, Channel 4’s Dispatches or the now defunct Granada series World in Action have rested on an image of conscientious ‘public service’. These popular, long running series have, at various points in their history, acted as the ‘conscience of the nation’, seeking to expose social injustice, investigate misdemeanours by the powerful and take on venal or corrupt vested interest. The BBC’s flagship current affairs series Panorama is Britain’s longest running television programme and, according to the Panorama website, ‘the world’s longest running investigative TV show’. It has provided a template for other current affairs series both in Britain, Europe and around the world while undergoing several transformations in form and style since its launch in 1953, the latest and arguably most dramatic being in 2007. This article will chart the development of Panorama as a distinctive, ‘flagship' current affairs series over six decades. It will attempt to answer why the Panorama brand has survived so long, while so many other notable current affairs series have not. Using research and material from Bournemouth University’s Panorama Archive, the Video Active website, the BFI and other European archives this article explores the development of an iconic current affairs series that has, at different stages in its history, proved a template for other news and current affairs programmes. Various breaks and continuities are highlighted in Panorama’s history and identity, and an attempt will be made to characterise and specify the Panorama ‘brand’ and pinpoint the series’ successes and failures in reinventing itself in a rapidly changing media context

Myogenic progenitors contribute to open but not closed fracture repair

<p>Abstract</p> <p>Background</p> <p>Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.</p> <p>Methods</p> <p>We employed a <it>MyoD</it>-Cre⁺:Z/AP⁺conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a <it>human alkaline phosphatase (hAP) </it>reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.</p> <p>Results</p> <p>In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP⁺cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP⁺cells detected in the open fracture callus. At early stages of repair, many hAP⁺cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP⁺cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP⁺staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.</p> <p>Conclusions</p> <p>These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.</p> <p>Please see related article: <url>http://www.biomedcentral.com/1741-7015/9/136</url></p

Shaping Skeletal Growth by Modular Regulatory Elements in the Bmp5 Gene

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body

Interlocutions with passive revolution

© The Author(s) 2018. This article critically engages with debates on uneven and combined development and particularly the lack of attention given in this literature to accounts of spatial diversity in capitalism’s outward expansion as well as issues of Eurocentrism. Through interlocutions with Antonio Gramsci on his theorising of state formation and capitalist modernity and the notion of passive revolution, we draw out the internal relationship between the structuring condition of uneven and combined development and the class agency of passive revolution. Interlocuting with passive revolution places Antonio Gramsci firmly within a stream of classic social theory shaping considerations of capitalist modernity. As a result, by building on cognate theorising elsewhere, passive revolution can then be established as a lateral field of causality that necessarily grasps spatio-temporal dynamics linked to both state and subaltern class practices of transformation in social property relations, situated within the structuring conditions of uneven and combined development

Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders

Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is placed on critically evaluating research within the realm of cognitive neuropsychology that aims to elucidate the component processes of HAND across the domains of executive functions, motor skills, speeded information processing, episodic memory, attention/working memory, language, and visuoperception. In addition to clarifying the cognitive mechanisms of HAND (e.g., impaired cognitive control), the cognitive neuropsychology approach may enhance the ecological validity of neuroAIDS research and inform the development of much needed novel, targeted cognitive and behavioral therapies

Skeletal Muscle Phenotypically Converts and Selectively Inhibits Metastatic Cells in Mice

Skeletal muscle is rarely a site of malignant metastasis; the molecular and cellular basis for this rarity is not understood. We report that myogenic cells exert pronounced effects upon co-culture with metastatic melanoma (B16-F10) or carcinoma (LLC1) cells including conversion to the myogenic lineage in vitro and in vivo, as well as inhibition of melanin production in melanoma cells coupled with cytotoxic and cytostatic effects. No effect is seen with non-tumorigenic cells. Tumor suppression assays reveal that the muscle-mediated tumor suppressor effects do not generate resistant clones but function through the down-regulation of the transcription factor MiTF, a master regulator of melanocyte development and a melanoma oncogene. Our findings point to skeletal muscle as a source of therapeutic agents in the treatment of metastatic cancers

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients