Achieving an "enlightened" publications policy at the University of Glasgow

The University of Glasgow has led the way in open access developments since 2001. This article charts the progress of open access at Glasgow through the development of the DAEDALUS Project in 2002 to the launch of the University's repository, Enlighten. Key factors leading to the recent announcement of a mandate for the deposit of research publications are discussed, including the impact of the Research Assessment Exercise and the need for a central publications database at Glasgow

On the road to Enlighten-ment: establishing an institutional repository service for the University of Glasgow

Purpose – The purpose of this paper is to chart the development and growth of open access and institutional repositories at the University of Glasgow, Scotland from initial work in 2001 to the University's recently launched service, Enlighten. The University of Glasgow is a signatory to the Scottish Open Access Declaration and recently released a statement on Open Access.<p></p> Design/methodology/approach – The study will focus on the key lessons learned through a twin track approach of advocacy and service development during the DAEDALUS Project (2002-2005) and the transition of that work to a University service called Enlighten. This service includes a repository for published and peer-reviewed papers which has now had over 2 million hits and over 270,000 PDF downloads since it was established in February 2004.<p></p> Findings – The paper reveals the lessons learned by the Library and the project team. It also identifies the range of issues which must be addressed in the successful implementation of a repository and its transition to a production service. These include the development of content policies, copyright clearance and the cultural change necessary to populate a repository service. These challenges have and continue to be addressed by the repository team at the University of Glasgow.<p></p> Originality/value – This paper provides details of the lessons learned in the practical experience of setting up an institutional repository and ensuring its transition to a full and supported University service. It will be of particular interest to institutions implementing a repository or running a pilot service.<p></p&gt

Saccharomyces cerevisiae: a nomadic yeast with no niche?

Different species are usually thought to have specific adaptations, which allow them to occupy different ecological niches. But recent neutral ecology theory suggests that species diversity can simply be the result of random sampling, due to finite population sizes and limited dispersal. Neutral models predict that species are not necessarily adapted to specific niches, but are functionally equivalent across a range of habitats. Here we evaluate the ecology of S. cerevisiae, one of the most important microbial species in human history. The artificial collection, concentration, and fermentation of large volumes of fruit for alcohol production produces an environment in which S. cerevisiae thrives, and therefore it is assumed that fruit is the ecological niche that S. cerevisiae inhabits and has adapted to. We find very little direct evidence that S. cerevisiae is adapted to fruit, or indeed to any other specific niche. We propose instead a neutral nomad model for S. cerevisiae, which we believe should be used as the starting hypothesis in attempting to unravel the ecology of this important microbe

The Success of Gay–Straight Alliances in Waterloo Region, Ontario: A Confluence of Political and Social Factors

This article outlines how gay–straight alliances (GSAs) work to connect youth with community resources, and outlines the political and social context of GSAs in Waterloo Region, Ontario, Canada. Fifteen individuals (youth, teachers, and a lesbian, gay, bisexual, transgender, and queer [LGBTQ] youth service provider) participated in interviews about the role of GSAs in creating supportive school environments for LGBTQ youth and their allies. Analyses of the interview data found that, apart from providing direct support to LGBTQ students, GSAs in Waterloo Region decrease isolation by connecting youth with other LGBTQ community members, events, and resources. This article discusses how the confluence of government and school board policy and community agency support facilitates the implementation, maintenance, and success of GSAs

In Vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish embryo and chicken embryo model systems

This study was supported by a Wellcome Trust-NIH PhD Studentship to SB, WDF and NV. Grant number 098252/Z/12/Z. SB, CHC and WDF are supported by the Intramural Research Program, NCI, NIH. NHG and WL are supported by the Intramural Research Program, NIA, NIH.Peer reviewedPublisher PD

Cultural transmission and optimization dynamics

We study the one-dimensional version of Axelrod's model of cultural transmission from the point of view of optimization dynamics. We show the existence of a Lyapunov potential for the dynamics. The global minimum of the potential, or optimum state, is the monocultural uniform state, which is reached for an initial diversity of the population below a critical value. Above this value, the dynamics settles in a multicultural or polarized state. These multicultural attractors are not local minima of the potential, so that any small perturbation initiates the search for the optimum state. Cultural drift is modelled by such perturbations acting at a finite rate. If the noise rate is small, the system reaches the optimum monocultural state. However, if the noise rate is above a critical value, that depends on the system size, noise sustains a polarized dynamical state.Comment: 11 pages, 10 figures include

The alpha-synuclein 5'untranslated region targeted translation blockers: anti-alpha synuclein efficacy of cardiac glycosides and Posiphen

Increased brain α-synuclein (SNCA) protein expression resulting from gene duplication and triplication can cause a familial form of Parkinson's disease (PD). Dopaminergic neurons exhibit elevated iron levels that can accelerate toxic SNCA fibril formation. Examinations of human post mortem brain have shown that while mRNA levels for SNCA in PD have been shown to be either unchanged or decreased with respect to healthy controls, higher levels of insoluble protein occurs during PD progression. We show evidence that SNCA can be regulated via the 5'untranslated region (5'UTR) of its transcript, which we modeled to fold into a unique RNA stem loop with a CAGUGN apical loop similar to that encoded in the canonical iron-responsive element (IRE) of L- and H-ferritin mRNAs. The SNCA IRE-like stem loop spans the two exons that encode its 5'UTR, whereas, by contrast, the H-ferritin 5'UTR is encoded by a single first exon. We screened a library of 720 natural products (NPs) for their capacity to inhibit SNCA 5'UTR driven luciferase expression. This screen identified several classes of NPs, including the plant cardiac glycosides, mycophenolic acid (an immunosuppressant and Fe chelator), and, additionally, posiphen was identified to repress SNCA 5'UTR conferred translation. Western blotting confirmed that Posiphen and the cardiac glycoside, strophanthidine, selectively blocked SNCA expression (~1 μM IC(50)) in neural cells. For Posiphen this inhibition was accelerated in the presence of iron, thus providing a known APP-directed lead with potential for use as a SNCA blocker for PD therapy. These are candidate drugs with the potential to limit toxic SNCA expression in the brains of PD patients and animal models in vivo

Global culture: A noise induced transition in finite systems

We analyze the effect of cultural drift, modeled as noise, in Axelrod's model for the dissemination of culture. The disordered multicultural configurations are found to be metastable. This general result is proven rigorously in d=1, where the dynamics is described in terms of a Lyapunov potential. In d=2, the dynamics is governed by the average relaxation time T of perturbations. Noise at a rate r 1/T sustains disorder. In the thermodynamic limit, the relaxation time diverges and global polarization persists in spite of a dynamics of local convergence.Comment: 4 pages, 5 figures. For related material visit http://www.imedea.uib.es/physdept

Lessons from a BACE1 inhibitor trial: off-site but not off base

Alzheimer's disease (AD) is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-β peptide (Aβ). The rate-limiting step in the production of Aβ is the processing of Aβ precursor protein (APP) by β-site APP-cleaving enzyme (BACE1). Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Aβ within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of β-galactoside α-2,6-sialyltransferase I (STGal6 I). In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future