Adult skeletal muscle stem cell migration is mediated by a blebbing/amoeboid mechanism

Adult skeletal muscle possesses a resident stem cell population called satellite cells which are responsible for tissue repair following damage. Satellite cell migration is crucial in promoting rapid tissue regeneration but is a poorly understood process. Furthermore, the mechanisms facilitating satellite cell movement have yet to be elucidated. Here the process of satellite cell migration has been investigated revealing that they undergo two distinct phases of movement; firstly under the basal lamina and then rapidly increasing their velocity when on the myofibre surface. Most significantly we show that satellite cells move using a highly dynamic blebbing based mechanism and not via lamellopodia mediated propulsion. We show that nitric oxide and non-canonical Wnt signalling pathways are necessary for regulating the formation of blebs and the migration of satellite cells. In summary, we propose that the formation of blebs and their necessity for satellite cell migration has significant implications in the future development of therapeutic regimes aimed at promoting skeletal muscle regeneration.

Early identification of stimulant treatment responders, partial responders and non-responders using objective measures in children and adolescents with hyperkinetic disorder

Background: The aim of this study was to evaluate stimulant medication response following a single dose of methylphenidate (MPH) in children and young people with hyperkinetic disorder using infrared motion analysis combined with a continuous performance task (QbTest system) as objective measures. The hypothesis was put forward that a moderate testdose of stimulant medication could determine a robust treatment response, partial response and non-response in relation to activity, attention and impulse control measures. Methods: The study included 44 children and young people between the ages of 7-18 years with a diagnosis of hyperkinetic disorder (F90 & F90.1). A single dose-protocol incorporated the time course effects of both immediate release MPH and extended release MPH (Concerta XL, Equasym XL) to determine comparable peak efficacy periods post intake. Results: A robust treatment response with objective measures reverting to the population mean was found in 37 participants (84%). Three participants (7%) demonstrated a partial response to MPH and four participants (9%) were determined as non-responders due to deteriorating activity measures together with no improvements in attention and impulse control measures. Conclusion: Objective measures provide early into prescribing the opportunity to measure treatment response and monitor adverse reactions to stimulant medication. Most treatment responders demonstrated an effective response to MPH on a moderate testdose facilitating a swift and more optimal titration process.

Supramolecular assemblies of metal ions in complex bimetallic and trimetallic salts based on hexacyanoferrate(III) ion

Two complex heterometallic salts with formulae Tl-6[Fe(CN)(6)](1) (33)(NO3)(OH) (1) and [Co(bpy)(2)(CN)(2)](2){[Ag(CN)(2)](0) (5)[Fe(CN)(6)](0) (5)} 8H(2)O (2) have been synthesized and fully characterized Single crystal X-ray analyses reveal that compound 1 is comprised of discrete Tl+ cations and [Fe(CN)(6)](3-) anions together with OH- and NO3- anions Compound 2 contains [Co(bpy)(2)(CN)(2)](+) cations and {[Ag(CN)(2)][Fe(CN)(6)]}(-) anions together with eight molecules of water of crystallization Both structures form unprecedented three-dimensional supramolecular networks via non covalent interactions Another important observation is that the stereochemically active inert (lone) pair present on Tl+ plays little role in controlling the structure of 1 The water molecules in 2 play important roles in providing stability organizing a supramolecular network through hydrogen bonding In the syntheses of 1 and 2 Fe(II) is oxidized to Fe(III) and Co(II) to Co(III) respectively facilitating the formation of the salts that are obtained Both compounds exhibit photoluminescence emission in solution near the visible region.

Ancient watercourses and biogeography of the Sahara explain the peopling of the desert

Evidence increasingly suggests that sub-Saharan Africa is at the center of human evolution and understanding routes of dispersal “out of Africa” is thus becoming increasingly important. The Sahara Desert is considered by many to be an obstacle to these dispersals and a Nile corridor route has been proposed to cross it. Here we provide evidence that the Sahara was not an effective barrier and indicate how both animals and humans populated it during past humid phases. Analysis of the zoogeography of the Sahara shows that more animals crossed via this route than used the Nile corridor. Furthermore, many of these species are aquatic. This dispersal was possible because during the Holocene humid period the region contained a series of linked lakes, rivers, and inland deltas comprising a large interlinked waterway, channeling water and animals into and across the Sahara, thus facilitating these dispersals. This system was last active in the early Holocene when many species appear to have occupied the entire Sahara. However, species that require deep water did not reach northern regions because of weak hydrological connections. Human dispersals were influenced by this distribution; Nilo-Saharan speakers hunting aquatic fauna with barbed bone points occupied the southern Sahara, while people hunting Savannah fauna with the bow and arrow spread southward. The dating of lacustrine sediments show that the “green Sahara” also existed during the last interglacial (∼125 ka) and provided green corridors that could have formed dispersal routes at a likely time for the migration of modern humans out of Africa.

Laughter in the Dark: ethical aspects of drama education

This chapter considers two questions. Firstly, in what ways might drama be an effective medium through which to explore difficult and sensitive issues that concern teenagers? And secondly, what ethical questions surround the use of drama to explore such issues? A practical workshop on teenage suicide is used as a platform for a discussion on the use and implications of different drama strategies and the role of humour as a critical lens and distancing device. The work of actual teenagers is used to illustrate the effectiveness of the techniques in both raising awareness and facilitating both critical and creative responses to the delicate issue explored in the workshop.

Limitations of the MRL mouse as a model for cardiac regeneration

Objective Myocardial repair following injury in mammals is restricted such that damaged areas are replaced by scar tissue, impairing cardiac function. MRL mice exhibit exceptional regenerative healing in an ear punch wound model. Some myocardial repair with restoration of heart function has also been reported following cryoinjury. Increased cardiomyocyte proliferation and a foetal liver stem cell population were implicated. We investigated molecular mechanisms facilitating myocardial repair in MRL mice to identify potential therapeutic targets in non-regenerative species. Methods Expressions of specific cell-cycle regulators that might account for regeneration (CDKs 1, 2, 4 and 6; cyclins A, E, D1 and B1; p21, p27 and E2F5) were compared by immunoblotting in MRL and control C57BL/6 ventricles during development. Flow cytometry was used to investigate stem cell populations in livers from foetal mice, and infarct sizes were compared in coronary artery-ligated and sham-treated MRL and C57BL/6 adult mice. Key findings No differences in the expressions of cell cycle regulators were observed between the two strains. Expressions of CD34+Sca1+ckit-, CD34+Sca1+ckit+ and CD34+Sca1-ckit+ increased in livers from C57BL/6 vs MRL mice. No differences were observed in infarct sizes, levels of fibrosis, Ki67 staining or cardiac function between MRL and C57BL/6 mice. Conclusions No intrinsic differences were observed in cell cycle control molecules or stem cell populations between MRL and control C57BL mouse hearts. Pathophysiologically relevant ischaemic injury is not repaired more efficiently in MRL myocardium, questioning the use of the MRL mouse as a reliable model for cardiac regeneration in response to pathophysiologically relevant forms of injury.

Reducing contamination by exposure plus safety behaviour

Background and objectives: It has been proposed that the judicious use of safety behaviour can facilitate improvements in the acceptability of cognitive behaviour therapy (CBT). It was decided to explore the possibility of facilitating CBT by introducing a form of safety behaviour.We sought to assess the degree to which Exposure plus Safety Behaviour (E þ SB) is an effective intervention for contamination fears. Methods: A comparison was made between the effects of a control condition (Exposure and Response Prevention; ERP) and an experimental condition (Exposure plus Safety Behaviour; E þ SB) in which each exposure to a contaminant was followed by the use of a hygienic wipe in a sample of (n ¼ 80) undergraduate students. In session one, each participant touched a confirmed contaminant 20 times. After each exposure participants were asked to report their feelings of contamination, fear, disgust, and danger. In the second session, two weeks later, the same procedure was carried out for a further 16 trials. Results: The ERP and the E þ SB conditions both produced large, significant and stable reductions in contamination. Significant reductions in fear, danger and disgust were also reported in both conditions. Limitations: The treatment was provided to an analogue sample and over two sessions. Conclusions: The use of hygienic wipes, the safety behaviour used in this experiment, did not preclude significant reductions in contamination, disgust, fear and danger. If it is replicated and extended over a longer time-frame, this finding may enable practitioners to enhance the acceptability of cognitive behavioural treatments and boost their effectiveness.

Poverty and livelihood diversification in rural Liberia: exploring the linkages between artisanal diamond mining and smallholder rice production

This paper provides an account of the changing livelihood dynamics unfolding in diamond-rich territories of rural Liberia. In these areas, many farm families are using the rice harvested on their plots to attract and feed labourers recruited specifically to mine for diamonds. The monies accrued from the sales of all recovered stones are divided evenly between the family and hired hands, an arrangement which, for thousands of people, has proved to be an effective short-term buffer against poverty. A deepened knowledge of these dynamics could be an important step towards facilitating lasting development in Liberia’s highly-impoverished rural areas.

The technocratic totalitarianism of construction process improvement: a critical perspective

The current research agenda for construction process improvement is heavily influenced by the rhetoric of business process re-engineering (BPR). In contrast to the wider literature on BPR, there is little evidence of critical thought within the construction management research community. A postmodernist interpretation is advocated whereby the reality of management practice is defined by the dominant management discourse. The persuasiveness of BPR rhetoric is analysed with particular reference to the way in which it plays on the insecurity of modern managers. Despite the lip service given to ‘empowerment’ and ‘teamwork’, the dominant theme of the re-engineering movement is that of technocratic totalitarianism. From a critical perspective, it is suggested that BPR is imposed on construction organizations to ensure continued control by the industry's dominant power groups. Whilst industry leaders are fond of calling for ‘attitudinal and cultural improvement’, the language of the accepted research agenda continually reinforces the industry's dominant culture of ‘control and command’. Therefore, current research directions in process improvement perpetuate existing attitudes rather than facilitating cultural change. The concept of lean construction is seen to be the latest manifestation of this phenomenon.

Identifying and investigating pesticide application types to promote a more sustainable pesticide use: the case of smallholders in Boyacá, Colombia

The present paper investigates pesticide application types adopted by smallholder potato producers in the Department of Boyacá , Colombia. In this region, environmental, health and adverse economic effects due to pesticide mis- or over-use respectively have been observed. Firstly, pesticide application types were identified based on input-effectiveness. Secondly, their determinants of adoption were investigated. Finally suggestions were given to develop intervention options for transition towards a more sustainable pesticide use. Three application types were identified for fungicide and insecticide. The types differed in terms of input (intensity of pesticide application), effect (damage control), frequency of application, average quantity applied per application, chemical class, and productivity. Then, the determinants of different pesticide application types were investigated with a multinomial logistic regression approach and applying the integrative agent centred (IAC) framework. The area of the plot, attendance at training sessions and educational and income levels were among the most relevant determinants. The analysis suggested that better pesticide use could be fostered to reduce pesticide-related risks in the region. Intervention options were outlined, which may help in targeting this issue. They aim not only at educating farmers, but to change their social and institutional context, by involving other agents of the agricultural system (i.e. pesticide producers), facilitating new institutional settings (i.e. cooperatives) and targeting social dynamics (i.e. conformity to social norms).

Exploring social barriers to adaptation: insights from Western Nepal

As the challenges and opportunities posed by climate change become increasingly apparent, the need for facilitating successful adaptation and enhancing adaptive capacity within the context of sustainable development is clear. With adaptation high on the agenda, the notion of limits and barriers to adaptation has recently received much attention within both academic and policymaking spheres. While emerging literature has been quick to depict limits and barriers in terms of natural, financial, or technologic processes, there is a clear shortfall in acknowledging social barriers to adaptation. It is against such a backdrop that this paper sets out to expose and explore some of the underlying features of social barriers to adaptation, drawing on insights from two case studies in the Western Nepal. This paper exposes the significant role of cognitive, normative and institutional factors in both influencing and prescribing adaptation. It explores how restrictive social environments can limit adaptation actions and influence adaptive capacity at the local level, particularly for the marginalised and socially excluded. The findings suggest a need for greater recognition of the diversity and complexity of social barriers, strategic planning and incorporation at national and local levels, as well as an emphasis on tackling the underlying drivers of vulnerability and social exclusion.

Winners and losers from industry reforms in the developing world: experiences from the electricity and mining sectors

The reform of previously state-owned and operated industries in many Less Developed Countries (LDCs) provide contrary experiences to those in the developed world, which have generally had more equitable distributional impacts. The economic reform policies proposed by the so-called 'Washington Consensus' state that privatisation provides governments with opportunities to raise revenues through the sale of under-performing and indebted state industries, thereby reducing significant fiscal burdens, and, at the same time, facilitating influxes of foreign capital, skills and technology, with the aim of improving operations and a "trickle-down" of benefits. However, experiences in many LDCs over the last 15-20 years suggest that reform has not solved the problem of chronic public-sector debt, and that poverty and socio-economic inequalities have increased during this period of 'neo-liberal' economics. This paper does not seek to challenge the policies themselves, but rather argues that the context in which reform has often taken place is of fundamental significance. The industry-centric policy advice provided by the IFIs typically causes a 'lock-in' of inequitably distributed 'efficiency gains', providing minimal, if any, benefits to impoverished groups. These arguments are made using case study analysis from the electricity and mining sectors.

Defining user perception of distributed multimedia quality

This article presents the results of a study that explored the human side of the multimedia experience. We propose a model that assesses quality variation from three distinct levels: the network, the media and the content levels; and from two views: the technical and the user perspective. By facilitating parameter variation at each of the quality levels and from each of the perspectives, we were able to examine their impact on user quality perception. Results show that a significant reduction in frame rate does not proportionally reduce the user's understanding of the presentation independent of technical parameters, that multimedia content type significantly impacts user information assimilation, user level of enjoyment, and user perception of quality, and that the device display type impacts user information assimilation and user perception of quality. Finally, to ensure the transfer of information, low-level abstraction (network-level) parameters, such as delay and jitter, should be adapted; to maintain the user's level of enjoyment, high-level abstraction quality parameters (content-level), such as the appropriate use of display screens, should be adapted.

Can microgrids make a major contribution to UK energy supply?

Almost all the electricity currently produced in the UK is generated as part of a centralised power system designed around large fossil fuel or nuclear power stations. This power system is robust and reliable but the efficiency of power generation is low, resulting in large quantities of waste heat. The principal aim of this paper is to investigate an alternative concept: the energy production by small scale generators in close proximity to the energy users, integrated into microgrids. Microgrids—de-centralised electricity generation combined with on-site production of heat—bear the promise of substantial environmental benefits, brought about by a higher energy efficiency and by facilitating the integration of renewable sources such as photovoltaic arrays or wind turbines. By virtue of good match between generation and load, microgrids have a low impact on the electricity network, despite a potentially significant level of generation by intermittent energy sources. The paper discusses the technical and economic issues associated with this novel concept, giving an overview of the generator technologies, the current regulatory framework in the UK, and the barriers that have to be overcome if microgrids are to make a major contribution to the UK energy supply. The focus of this study is a microgrid of domestic users powered by small Combined Heat and Power generators and photovoltaics. Focusing on the energy balance between the generation and load, it is found that the optimum combination of the generators in the microgrid- consisting of around 1.4 kWp PV array per household and 45% household ownership of micro-CHP generators- will maintain energy balance on a yearly basis if supplemented by energy storage of 2.7 kWh per household. We find that there is no fundamental technological reason why microgrids cannot contribute an appreciable part of the UK energy demand. Indeed, an estimate of cost indicates that the microgrids considered in this study would supply electricity at a cost comparable with the present electricity supply if the current support mechanisms for photovoltaics were maintained. Combining photovoltaics and micro-CHP and a small battery requirement gives a microgrid that is independent of the national electricity network. In the short term, this has particular benefits for remote communities but more wide-ranging possibilities open up in the medium to long term. Microgrids could meet the need to replace current generation nuclear and coal fired power stations, greatly reducing the demand on the transmission and distribution network.

Analysis of the intermediate housing market mechanism in the UK

Government policies have backed intermediate housing market mechanisms like shared equity, intermediate rented and shared ownership (SO) as potential routes for some households, who are otherwise squeezed between the social housing and the private market. The rhetoric deployed around such housing has regularly contained claims about its social progressiveness and role in facilitating socio-economic mobility, centring on a claim that SO schemes can encourage people to move from rented accommodation through a shared equity phase and into full owner-occupation. SO has been justified on the grounds of it being transitional state, rather than a permanent tenure. However SO buyers may be laden with economic cost-benefit structures that do not stack up evenly and as a consequence there may be little realistic prospect of ever reaching a preferred outcome. Such behaviours have received little empirical attention as yet despite, the SO model arguably offers a sub-optimal solution towards homeownership, or in terms of wider quality of life. Given the paucity of rigorous empirical work on this issue, this paper delineates the evidence so far and sets out a research agenda. Our analysis is based on a large dataset of new shared owners, observing an information base that spans the past decade. We then set out an agenda to further examine the behaviours of the SO occupants and to examine the implications for future public policy based on existing literature and our outline findings. This paper is particularly opportune at a time of economic uncertainty and an overriding ‘austerity’ drive in public funding in the UK, through which SO schemes have enjoyed support uninterruptedly thus far.