Transgenic Overexpression of LARGE Induces alpha-Dystroglycan Hyperglycosylation in Skeletal and Cardiac Muscle

Background: LARGE is one of seven putative or demonstrated glycosyltransferase enzymes defective in a common group of muscular dystrophies with reduced glycosylation of alpha-dystroglycan. Overexpression of LARGE induces hyperglycosylation of alpha-dystroglycan in both wild type and in cells from dystroglycanopathy patients, irrespective of their primary gene defect, restoring functional glycosylation. Viral delivery of LARGE to skeletal muscle in animal models of dystroglycanopathy has identical effects in vivo, suggesting that the restoration of functional glycosylation could have therapeutic applications in these disorders. Pharmacological strategies to upregulate Large expression are also being explored.Methodology/Principal Findings: In order to asses the safety and efficacy of long term LARGE over-expression in vivo, we have generated four mouse lines expressing a human LARGE transgene. On observation, LARGE transgenic mice were indistinguishable from the wild type littermates. Tissue analysis from young mice of all four lines showed a variable pattern of transgene expression: highest in skeletal and cardiac muscles, and lower in brain, kidney and liver. Transgene expression in striated muscles correlated with alpha-dystroglycan hyperglycosylation, as determined by immunoreactivity to antibody IIH6 and increased laminin binding on an overlay assay. Other components of the dystroglycan complex and extracellular matrix ligands were normally expressed, and general muscle histology was indistinguishable from wild type controls. Further detailed muscle physiological analysis demonstrated a loss of force in response to eccentric exercise in the older, but not in the younger mice, suggesting this deficit developed over time. However this remained a subclinical feature as no pathology was observed in older mice in any muscles including the diaphragm, which is sensitive to mechanical load-induced damage.Conclusions/Significance: This work shows that potential therapies in the dystroglycanopathies based on LARGE upregulation and alpha-dystroglycan hyperglycosylation in muscle should be safe

The effects of 118 years of industrial fishing on UK bottom trawl fisheries

This is the final version of the article. Available from Springer Nature via the DOI in this record.In 2009, the European Commission estimated that 88% of monitored marine fish stocks were overfished, on the basis of data that go back 20 to 40 years and depending on the species investigated. However, commercial sea fishing goes back centuries, calling into question the validity of management conclusions drawn from recent data. We compiled statistics of annual demersal fish landings from bottom trawl catches landing in England and Wales dating back to 1889, using previously neglected UK Government data. We then corrected the figures for increases in fishing power over time and a recent shift in the proportion of fish landed abroad to estimate the change in landings per unit of fishing power (LPUP), a measure of the commercial productivity of fisheries. LPUP reduced by 94% - 17-fold - over the past 118 years. This implies an extraordinary decline in the availability of bottom-living fish and a profound reorganization of seabed ecosystems since the nineteenth century industrialization of fishing.R.H.T. was supported by Natural England and a Mia J. Tegner Memorial Research Grant. S.B. was supported by a Ray Lankester Investigatorship from the Marine Biological Association of the United Kingdom

Conservation and concealment in SpeciesBanking.com, USA: an analysis of neoliberal performance in the species offsetting industry

Market-based strategies are promoted as neoliberal governance solutions to environmental problems, from local to global scales. Tradable mitigation schemes are proliferating. These include species banking, which enables payments for the purchase of species credits awarded to conserved areas to offset development impacts on protected species elsewhere. An analysis of species banks in the USA through a survey of data from the website www.SpeciesBanking.com (established as a ‘clearing house’ for species banking information) was complemented by questionnaire material from USA bank managers. The number of USA species banks has increased rapidly, bank area ownership and management is consolidated in a small number of organizations, and public information on species credit price is limited. In interrogating the case material, the roles of specific economic policies associated with neoliberalism are considered, focusing on the extension of privatization, de- and re-regulation and marketization into the arena of environmental conservation, and commodification processes as manifested in species banking. Problematic ecological and distributive ‘concealments’ in species banking include the ‘development-led’ nature of conservation banking, tendencies towards net biodiversity loss, and an emphasis on supporting conservation-related wealth accumulation by larger landowners and investors

From pyramid to pointed egg? A 20-year perspective on poverty, prosperity and rural transformation in Tanzania

This article analyses patterns of poverty, prosperity and rural transformation in Tanzania through longitudinal research examining livelihoods and asset change in a twenty-year period. We argue that some current measures of rural transformation are inadequate for capturing forms of change that matter to rural Africans. We consider in detail some of the processes that lie behind such change in selected locations in Morogoro region, noting the importance of improvements that are taking place through smallholder agriculture. In concluding, the article discusses the implications of these findings for agricultural policy, while also cautioning about the blindness of our methods to other forms of poverty

Towards a synthesized critique of neoliberal biodiversity conservation

During the last three decades, the arena of biodiversity conservation has largely aligned itself with the globally dominant political ideology of neoliberalism and associated governmentalities. Schemes such as payments for ecological services are promoted to reach the multiple ‘wins’ so desired: improved biodiversity conservation, economic development, (international) cooperation and poverty alleviation, amongst others. While critical scholarship with respect to understanding the linkages between neoliberalism, capitalism and the environment has a long tradition, a synthesized critique of neoliberal conservation - the ideology (and related practices) that the salvation of nature requires capitalist expansion - remains lacking. This paper aims to provide such a critique. We commence with the assertion that there has been a conflation between ‘economics’ and neoliberal ideology in conservation thinking and implementation. As a result, we argue, it becomes easier to distinguish the main problems that neoliberal win-win models pose for biodiversity conservation. These are framed around three points: the stimulation of contradictions; appropriation and misrepresentation and the disciplining of dissent. Inspired by Bruno Latour’s recent ‘compositionist manifesto’, the conclusion outlines some ideas for moving beyond critique

Celebrity Coverage

Celebrity coverage is defined as mediated attention provided to well‐known individuals who through their state of fame become newsworthy. Coverage of celebrities ranges from stories about famous people in categories such as Hollywood, sports, politics, and music as well as celebrities who become famous through digital media. Celebrity journalism focuses on the process of becoming famous, known as the celebrification of individuals, and the influence celebrities have on politics, culture, and activism known as celebritization. Through an increasing interest in its content, celebrity coverage has turned into an economic good for media organizations. While celebrities continue to rely on mass media channels, digital media have changed not only celebrity culture, but also celebrity journalism