Protein deiminases: new players in the developmentally regulated loss of neural regenerative ability

Spinal cord regenerative ability is lost with development, but the mechanisms underlying this loss are still poorly understood. In chick embryos, effective regeneration does not occur after E13, when spinal cord injury induces extensive apoptotic response and tissue damage. As initial experiments showed that treatment with a calcium chelator after spinal cord injury reduced apoptosis and cavitation, we hypothesized that developmentally regulated mediators of calcium-dependent processes in secondary injury response may contribute to loss of regenerative ability. To this purpose we screened for such changes in chick spinal cords at stages of development permissive (E11) and non-permissive (E15) for regeneration. Among the developmentally regulated calcium-dependent proteins identified was PAD3, a member of the peptidylarginine deiminase (PAD) enzyme family that converts protein arginine residues to citrulline, a process known as deimination or citrullination. This post-translational modification has not been previously associated with response to injury. Following injury, PAD3 up-regulation was greater in spinal cords injured at E15 than at E11. Consistent with these differences in gene expression, deimination was more extensive at the non-regenerating stage, E15, both in the gray and white matter. As deimination paralleled the extent of apoptosis, we investigated the effect of blocking PAD activity on cell death and deiminated-histone 3, one of the PAD targets we identified by mass-spectrometry analysis of spinal cord deiminated proteins. Treatment with the PAD inhibitor, Cl-amidine, reduced the abundance of deiminated-histone 3, consistent with inhibition of PAD activity, and significantly reduced apoptosis and tissue loss following injury at E15. Altogether, our findings identify PADs and deimination as developmentally regulated modulators of secondary injury response, and suggest that PADs might be valuable therapeutic targets for spinal cord injury.

Can the European low-cost airline boom continue? Implications for regional airports

At a time when the traditional major airlines have struggled to remain viable, the low-cost carriers have become the major success story of the European airline industry. This paper looks behind the headlines to show that although low-cost airlines have achieved much, they too have potential weaknesses and face a number of challenges in the years ahead. The secondary and regional airports that have benefited from low-cost carrier expansion are shown to be vulnerable to future changes in airline economics, government policy and patterns of air service. An analysis of routes from London demonstrates that the low-cost airlines have been more successful in some markets than others. To attractive and historically under-served leisure destinations in Southern Europe they have stimulated dramatic growth and achieved a dominant position. To major hub cities however they typically remain marginal players and to secondary points in Northern Europe their traffic has been largely diverted from existing operators. There is also evidence that the UK market is becoming saturated and new low-cost services are poaching traffic from other low-cost routes. Passenger compensation legislation and possible environmental taxes will hit the low-cost airline industry disproportionately hard. The high elasticities of demand to price in certain markets that these airlines have exploited will operate in reverse. One of the major elements of the low-cost business model involves the use of smaller uncongested airports. These offer faster turn-arounds and lower airport charges. In many cases, local and regional government has been willing to subsidise expansion of air services to assist with economic development or tourism objectives. However, recent court cases against Ryanair now threaten these financial arrangements. The paper also examines the catchment areas for airports with low-cost service. It is shown that as well as stimulating local demand, much traffic is captured from larger markets nearby through the differential in fare levels. This has implications for surface transport, as access to these regional airports often involves long journeys by private car. Consideration is then given to the feasibility of low-cost airlines expanding into the long-haul market or to regional operations with small aircraft. Many of the cost advantages are more muted on intercontinental services.

The BBC's role in the changing production ecology of pre-school television in Britain

This paper examines the changing production ecology of British pre-school television in light of developments since the mid-1990s and the specific role played by the BBC. Underpinning the research is the perception that pre-school television is characterised by a complex set of industry relationships and dependencies that demands content which needs to satisfy a wide range of international circumstances and commercial prerogatives. For the BBC this has created tension between its public service goals and commercial priorities. Pre-school programming began in Britain in 1950, but it was not until the mid-1990s that Britain emerged as a leading producer of pre-school programming worldwide with government/industry reports regularly identifying the children’s production sector as an important contributor to exports. The rise of pre-school niche channels (CBeebies, Nick Junior, Playhouse Disney), audience fragmentation and the internationalisation and commercialisation of markets have radically altered the funding base of children’s television and the relationships that the BBC enjoys with key players. The international success of much of its pre-school programming is based on the relationships it enjoys with independent producers who generate significant revenues from programme-related consumer products. This paper focuses on the complex and changing relationships between the BBC, independent producers, and financiers, that constitute the production ecology of pre-school television and shape its output. Within the broader setting of cultural production and global trends the paper investigates the following questions: 1) In the light of changes to the sector since the mid-1990s, what makes pre-school television significant both generally and as an ideal public service project? 2) What is the nature of the current funding crisis in British children’s television and what implications does this crisis have for the BBC’s involvement in pre-school television? 3) How is the Corporation reacting to and managing the wider commercial, cultural, regulatory and technological forces that are likely to affect its strategies for the commissioning, production and acquisition of pre-school content?

Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment

The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias

Media ‘Globalization’ as Survival Strategy for Authoritarian Regimes In the Arab Middle East

Sakr challenges the notion that transnational media technologies have forced states in the Arab Middle East to cede ever more control to non-state players since the 1990s. Taking account of a long history of foreign political engineering in Arab countries, she probes the realities of Arab broadcasting privatization, intra-regional harmonization of government communication policies, and external financial support for media freedom and reform, to show how Arab governments were large successfully in harnessing forces implicated in media globalization in a way that entrenched authoritarian elements of the status quo. The findings validate an alternative to globalization theory that places a dual focus on the agency of national ruling elites and the international structures that underpin the power of those elites today, as in the past.

Teacher educators: proposing new professional development models within an English further education context

At a time of increasing public and government focus on the quality of teacher education, little is known about the professional development needs of those who teach teachers in further education (FE). Yet they are crucial players. Efforts are intensifying across a significant number of countries to promote the professional development of teacher educators, but there is little support for new or experienced practitioners and no substantive professional standards regarding this role in English FE. This has an impact on the professional practice and career trajectories of teacher educators themselves. Based on a series of semi-structured interviews, an online survey and focus groups, this mixed-methods study uses a sequential exploratory design. The study captures the voices of English FE teacher educators who identified mentoring, induction and a choice of continuous professional development sessions as important strategies to improve the effectiveness of their role over time. This article will propose flexible models of professional development, following an analysis of new and experienced teacher educators’ needs in FE in England. The article recommends that new professional standards for teacher educators could be written collaboratively by practitioners, within a policy and institutional framework which supports the scholarship and research requirements of teacher educators.