129 research outputs found

    The limits of discourse: masculinity as vulnerability

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    For many, gender equity being fair to women and men is a zero sum game in which men should be willing to give up their privileges for the creation of a more equitable and just society. The idea that men might benefit from gender equity seems, for many, unthinkable. This was brought home a few years ago in a gender studies test, when students answering a question on what men might gain from gender equality explained instead how women would benefit. In this Perspective I reflect on the ways in which popular discourses around gender may inadvertently undermine movement towards gender and social justice. Dismissing my students' answers as the result of poor teaching or learning misses a key point: It seems to be extraordinarily difficult for most people to recognise how gender creates masculine vulnerabilities or how gender equity could benefit men. I suggest that if we are to improve women's lives through the reduction of violence, feminist teachers and activists need to think creatively about how to help men and boys understand that performances of masculinity deeply compromise their own lives

    Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

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    Molecular groups of supratentorial ependymomas comprise tumors with ZFTA-RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally supratentorial ependymomas cannot be readily assigned to any of these groups due to lack of detection of a typical fusion and/or ambiguous DNA methylation-based classification. An unbiased approach with a cohort of unprecedented size revealed distinct methylation clusters composed of tumors with ependymal but also various other histological features containing alternative translocations that shared ZFTA as a partner gene. Somatic overexpression of ZFTA-associated fusion genes in the developing cerebral cortex is capable of inducing tumor formation in vivo, and cross-species comparative analyses identified GLI2 as a key downstream regulator of tumorigenesis in all tumors. Targeting GLI2 with arsenic trioxide caused extended survival of tumor-bearing animals, indicating a potential therapeutic vulnerability in ZFTA fusion-positive tumors

    Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

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    <p>Abstract</p> <p>Background</p> <p>Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (<it>PLK1</it>) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy.</p> <p>Methods</p> <p>We examined the expression of <it>PLK1 </it>mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting <it>PLK1 </it>mRNA on tumor-initiating cells was evaluated using tumor sphere assays.</p> <p>Results</p> <p>Analysis of gene expression in two independent cohorts revealed that <it>PLK1 </it>mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (<it>SOX2</it>) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells.</p> <p>Conclusions</p> <p>Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation.</p

    An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

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    Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.We are grateful to F.B. Gertler (Massachusetts Institute of Technology) and S. Gupton (University of North Carolina) for the generous gift of the VAMP7-phlorin construct and the staffs of the Hartwell Center for Bioinformatics and Biotechnology, the Small Animal Imaging Center, the Animal Resources Center, the Cell and Tissue Imaging Center, and the Flow Cytometry and Cell Sorting Shared Resource at St. Jude Children's Research Hospital for technical assistance. This work was supported by grants from the US National Institutes of Health (R01CA129541, P01CA96832 and P30CA021765, R.J.G.), by the Collaborative Ependymoma Research Network (CERN) and by the American Lebanese Syrian Associated Charities (ALSAC)

    Prisoners’ Families’ Research: Developments, Debates and Directions

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    After many years of relative obscurity, research on prisoners’ families has gained significant momentum. It has expanded from case-oriented descriptive analyses of family experiences to longitudinal studies of child and family development and even macro analyses of the effects on communities in societies of mass incarceration. Now the field engages multi-disciplinary and international interest although it arguably still remains on the periphery of mainstream criminological, psychological and sociological research agendas. This chapter discusses developments in prisoners’ families’ research and its positioning in academia and practice. It does not aim to provide an all-encompassing review of the literature rather it will offer some reflections on how and why the field has developed as it has and on its future directions. The chapter is divided into three parts. The first discusses reasons for the historically small body of research on prisoners’ families and for the growth in research interest over the past two decades. The second analyses patterns and shifts in the focus of research studies and considers how the field has been shaped by intersecting disciplinary interests of psychology, sociology, criminology and socio-legal studies. The final part reflects on substantive and ethical issues that are likely to shape the direction of prisoners’ families’ research in the future

    Eco-politics beyond the paradigm of sustainability: A conceptual framework and research agenda

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    This contribution sketches a conceptual framework for the analysis of the post-ecologist era and outlines a research agenda for investigating its politics of unsustainability. The article suggests that this new era and its particular mode of eco-politics necessitate a new environmental sociology. Following a review of some achievements and limitations of the paradigm of sustainability, the concept of post-ecologism is related to existing discourses of the ‘end of nature’, the ‘green backlash’ and the ‘death of environmentalism’. The shifting terrain of eco-politics in the late-modern condition is mapped and an eco-sociological research programme outlined centring on the post-ecologist question: How do advanced modern capitalist consumer democracies try and manage to sustain what is known to be unsustainable

    Traditional and transgenic strategies for controlling tomato-infecting begomoviruses

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    Cannabis and other drug use among trauma patients in three South African cities, 1999-2001

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    CITATION: Parry, C. D. H. et al. 2005. Cannabis and other drug use among trauma patients in three South African cities, 1999-2001. South African Medical Journal, 95(6):429-432.The original publication is available at http://www.samj.org.zaObjective. To assess the extent of cannabis and other drug use among patients presenting with recent injuries at trauma units in Cape Town, Port Elizabeth and Durban from 1999 to 2001. Design. Cross-sectional surveys were conducted during a 4-week period at each of the above sites in 1999, 2000 and 2001. The concept of an idealised week was used to render representative samples. Outcome measures. Cause of injury and biological markers to assess use of cannabis, methaqualone (Mandrax), opiates, cocaine, amphetamine, and methamphetamine. Results. Over half of all patients tested experienced violent injuries. Excluding opiates, across sites and over time between 33% and 62% of patients tested positive for at least one drug (N = 1 565). In most cases the drugs were cannabis and/or methaqualone. While no inter-city differences were found, male patients were typically more likely to test positive for drugs in general and specific drugs such as cannabis and the cannabis/methaqualone ('white pipe') combination than female patients. Drug positivity was higher in 2001 than in the previous 2 years in Cape Town, and patients injured as a result of violence in Cape Town and Durban were more likely to test positive for drugs than patients with certain other types of injuries. Conclusions. Drug use among trauma patients has remained consistently high for each of the 3 study periods. Efforts to combat the abuse of drugs such as cannabis and methaqualone would appear to be paramount in reducing the burden of injuries on health care services. The study has raised numerous issues requiring further research.Publisher’s versio
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