'Both kinds in one/Both male and female': Ate, Lust and hermaphroditic Venus in Book IV of Edmund Spenser's The Faerie Queene

This is a PDF version of a working paper published in 1996. ©Graham Atkin and Chester College.This working paper, originally delivered at the Voicing Women conference at the University of Liverpool in April 1992, discusses Book IV of The Faerie Queene by Edmund Spenser. The paper focuses on the figures of "Ate, mother of debate", Lust, the androgynous Venus, and the love story of Amoret and Scudamour

The Role of F-box Only Protein 2 (Fbxo2) in Amyloid Precursor Protein Processing and Synaptic Dynamics.

Proper protein quality control is essential for neuronal health and function, and there is substantial evidence for the dysregulation of proteostasis in a wide range of neuropathological conditions including the most common neurodegenerative diseases. Diminished function of the Ubiquitin Proteasome System, the major cellular pathway for the clearance of toxic or unwanted proteins, likely contributes to disease pathogenesis through numerous - and as yet, incompletely understood - mechanisms. Here, I review recent studies exploring the role of the Ubiquitin Proteasome System in the most common neurodegenerative diseases. I then describe in-depth two research projects directed at further investigating one agent of the Ubiquitin Proteasome System whose expression is reduced in Alzheimer’s disease, the F-box Only Protein 2 (Fbxo2). Using cell-based models and an Fbxo2 knockout mouse, I present evidence for a role for Fbxo2 in the turnover and processing of the Amyloid Precursor Protein, believed to be the major causative protein in Alzheimer’s disease. I then show that the loss of Fbxo2 results in greater expression and surface localization of NMDA receptor subunits, and enhances the formation of axo-dendritic shaft synapses. Taken together, these studies support a central role for the Ubiquitin Proteasome System, and in particular Fbxo2, in the turnover and handling of key proteins in the pathogenesis of Alzheimer’s disease and the regulation of synaptic connections.PhDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107118/1/atking_1.pd

Developmental expression of BK channels in chick cochlear hair cells

<p>Abstract</p> <p>Background</p> <p>Cochlear hair cells are high-frequency sensory receptors. At the onset of hearing, hair cells acquire fast, calcium-activated potassium (BK) currents, turning immature spiking cells into functional receptors. In non-mammalian vertebrates, the number and kinetics of BK channels are varied systematically along the frequency-axis of the cochlea giving rise to an intrinsic electrical tuning mechanism. The processes that control the appearance and heterogeneity of hair cell BK currents remain unclear.</p> <p>Results</p> <p>Quantitative PCR results showed a non-monotonic increase in BK α subunit expression throughout embryonic development of the chick auditory organ (i.e. basilar papilla). Expression peaked near embryonic day (E) 19 with six times the transcript level of E11 sensory epithelia. The steady increase in gene expression from E11 to E19 could not explain the sudden acquisition of currents at E18-19, implicating post-transcriptional mechanisms. Protein expression also preceded function but progressed in a sequence from diffuse cytoplasmic staining at early ages to punctate membrane-bound clusters at E18. Electrophysiology data confirmed a continued refinement of BK trafficking from E18 to E20, indicating a translocation of BK clusters from supranuclear to subnuclear domains over this critical developmental age.</p> <p>Conclusions</p> <p>Gene products encoding BK α subunits are detected up to 8 days before the acquisition of anti-BK clusters and functional BK currents. Therefore, post-transcriptional mechanisms seem to play a key role in the delayed emergence of calcium-sensitive currents. We suggest that regulation of translation and trafficking of functional α subunits, near voltage-gated calcium channels, leads to functional BK currents at the onset of hearing.</p

Implications for public health research of models and theories of disability: A scoping study and evidence synthesis

Open access articleBackground: Public health interventions that are effective in the general population are often assumed to apply to people with impairments. However, the evidence to support this is limited and hence there is a need for public health research to take a more explicit account of disability and the perspectives of people with impairments. Objectives: (1) To examine the literature on theories and models of disability; (2) to assess whether or not, and how, intervention studies of effectiveness could incorporate more inclusive approaches that are consistent with these theories and models; and (3) to use the findings to draw out implications for improving evaluative study designs and evidence-based practice. Review methods: The project is a scoping review of the literature. The first stage examines theories and models of disability and reflects on possible connections between theories of disability and public health paradigms. This discussion is used to develop an ethical–empirical decision aid/checklist, informed by a human rights approach to disability and ecological approaches to public health. We apply this decision aid in the second stage of the review to evaluate the extent to which the 30 generic public health reviews of interventions and the 30 disability-specific public health interventions include the diverse experiences of disability. Five deliberation panels were also organised to further refine the decision aid: one with health-care professionals and four with politically and socially active disabled people. Results: The evidence from the review indicated that there has been limited public health engagement with theories and models of disability. Outcome measures were often insensitive to the experiences of disability. Even when disabled people were included, studies rarely engaged with their experiences in any meaningful way. More inclusive research should reflect how people live and ‘flourish’ with disability. Limitations: The scoping review provides a broad appraisal of a particular field. It generates ideas for future practice rather than a definite framework for action. Conclusions: Our ethical–empirical decision aid offers a critical framework with which to evaluate current research practice. It also offers a resource for promoting more ethical and evidence-based public health research that is methodologically robust while being sensitive to the experiences of disability. Future work: Developing more inclusive research and interventions that avoid conceptualising disability as either a ‘burden’ or ‘problem’ is an important starting point. This includes exploring ways of refining and validating current common outcome measures to ensure that they capture a diverse range of disabling experiences, as well as generating evidence on meaningful ways of engaging a broad range of disabled children and adults in the research process

A scheme for determining vehicle routes based on Arc-based service network design

In freight transportation, less-than-truckload carriers often need to assign each vehicle a cyclic route so that drivers can come back home after a certain period of time. However, the Node-Arc model for service network design addresses decisions on each arc and does not determine routes directly, although the vehicle balancing constraint ensures that the number of outgoing vehicles equals the number of incoming vehicles at each node. How to transform the optimized service network into a set of vehicle routes remains an important problem that has not yet been studied. In this paper, we propose a three-phase scheme to address this problem. In the first stage, we present an algorithm based on the depth-first search to find all of the different cyclic routes in a service network design solution. In the second stage, we propose to prune poor cyclic routes using real-life constraints so that a collection of acceptable vehicle routes can be obtained before route assignment. Some of the pruning can also be done in the first stage to speed up the proposed algorithm. In the third stage, we formulate the problem of selecting a set of cyclic routes to cover the entire network as a weighted set covering problem. The resulting model is formulated as an integer program and solved with IBM ILOG CPLEX solver. Experimental results on benchmark instances for service network design indicate the effectiveness of the proposed scheme which gives high-quality solutions in an efficient way

Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity

NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance

Impact of soil warming and shading on colonization and community structure of arbuscular mycorrhizal fungi in roots of a native grassland

Arbuscular mycorrhizal (AM) fungi have a major influence on the structure, responses and below-ground C allocation of plant communities. Our lack of understanding of the response of AM fungi to factors such as light and temperature is an obstacle to accurate prediction of the impact of global climate change on ecosystem functioning. In order to investigate this response, we divided a grassland site into 24 plots, each either unshaded or partly shaded with soil either unheated or heated by 3°C at 2 cm depth. In both short-term studies in spring and autumn, and in a 1-year-long study, we measured root length colonization (LRC) by AM and non-AM fungi. For selected root samples, DNA sequences were amplified by PCR with fungal-specific primers for part of the small sub-unit (SSU) rRNA gene. In spring, the total LRC increased over 6 weeks from 12% to 25%. Shading significantly reduced AM but increased non-AM fungal colonization, while soil warming had no effect. In the year-long study, colonization by AM fungi peaked in summer, whereas non-AM colonization peaked in autumn, when there was an additive effect of shading and soil warming that reduced AM but increased non-AM fungi. Stepwise regression revealed that light received within the 7 days prior to sampling was the most significant factor in determining AM LRC and that mean temperature was the most important influence on non-AM LRC. Loglinear analysis confirmed that there were no seasonal or treatment effects on the host plant community. Ten AM fungal sequence types were identified that clustered into two families of the Glomales, Glomaceae and Gigasporaceae. Three other sequence types were of non-AM fungi, all Ascomycotina. AM sequence types showed seasonal variation and shading impacts: loglinear regression analysis revealed changes in the AM fungal community with time, and a reduction of one Glomus sp. under shade, which corresponded to a decrease in the abundance of Trifolium repens. We suggest that further research investigating any impacts of climate change on ecosystem functioning must not only incorporate their natural AM fungal communities but should also focus on niche separation and community dynamics of AM fungi

A novel approach to independent taxi scheduling problem based on stable matching

This paper describes a taxi scheduling system, which aims to improve the overall efficiency of the system, both from the perspective of the drivers and the customers. This is of particular relevance to Chinese cities, where hailing a taxi on the street is by far the most common way in which taxis are requested, since the majority of taxi drivers operate independently, rather than working for a company. The mobile phone and GPS-based taxi scheduling system, which is described in this paper, aims to provide a decision support system for taxi drivers and facilitates direct information exchange between taxi drivers and passengers, while allowing drivers to remain independent. The taxi scheduling problem is considered to be a non-cooperative game between taxi drivers and a description of this problem is given. We adopt an efficient algorithm to discover a Nash equilibrium, such that each taxi driver and passenger cannot benefit from changing their assigned partner. Two computational examples are given to illustrate the effectiveness of the approach

The Influence of 9-marathons completed in 9 days on injury incidence and selected musculoskeletal tests.

Multi-day running events are increasingly popular however, research in these events is lacking and fails to consider the dynamic nature of musculoskeletal physiology. Twenty-three athletes completing a ten-day marathon event participated in the study. Proprioception, dynamic balance, knee valgus and flexibility were assessed the day before the event and after one, five and nine consecutive marathons. There were significant reductions in these measurements across the event and reductions were more apparent in the non-dominant side. Each runner suffered on average 4.2 injuries. Runners performed significantly worse in musculoskeletal measurements, particularly on the non-dominant side, as the competition progresses. Therefore, athletic trainers should design appropriate between-day recovery strategies during events based on with-in event data collection