Variation in Array Size, Monomer Composition and Expression of the Macrosatellite DXZ4

Macrosatellites are some of the most polymorphic regions of the human genome, yet many remain uncharacterized despite the association of some arrays with disease susceptibility. This study sought to explore the polymorphic nature of the X-linked macrosatellite DXZ4. Four aspects of DXZ4 were explored in detail, including tandem repeat copy number variation, array instability, monomer sequence polymorphism and array expression. DXZ4 arrays contained between 12 and 100 3.0 kb repeat units with an average array containing 57. Monomers were confirmed to be arranged in uninterrupted tandem arrays by restriction digest analysis and extended fiber FISH, and therefore DXZ4 encompasses 36–288 kb of Xq23. Transmission of DXZ4 through three generations in three families displayed a high degree of meiotic instability (8.3%), consistent with other macrosatellite arrays, further highlighting the unstable nature of these sequences in the human genome. Subcloning and sequencing of complete DXZ4 monomers identified numerous single nucleotide polymorphisms and alleles for the three microsatellite repeats located within each monomer. Pairwise comparisons of DXZ4 monomer sequences revealed that repeat units from an array are more similar to one another than those originating from different arrays. RNA fluorescence in situ hybridization revealed significant variation in DXZ4 expression both within and between cell lines. DXZ4 transcripts could be detected originiating from both the active and inactive X chromosome. Expression levels of DXZ4 varied significantly between males, but did not relate to the size of the array, nor did inheritance of the same array result in similar expression levels. Collectively, these studies provide considerable insight into the polymorphic nature of DXZ4, further highlighting the instability and variation potential of macrosatellites in the human genome

Social Media, Professional Media, and Mobilization in Contemporary Britain:Explaining the Strengths and Weaknesses of the Citizens’ Movement 38 Degrees

This article was published in the journal Political Studies [SAGE © The Author(s)] and the definitive version is available at: https://doi.org/10.1177/0032321716631350Digital media continue to reshape political activism in unexpected ways. Within a period of a few years, the internet-enabled UK citizens’ movement 38 Degrees has amassed a membership of 3 million and now sits alongside similar entities such as America’s MoveOn, Australia’s GetUp! and the transnational movement Avaaz. In this article, we contribute to current thinking about digital media and mobilisation by addressing some of the limitations of existing research on these movements and on digital activism more generally. We show how 38 Degrees’ digital network repertoires coexist interdependently with its strategy of gaining professional news media coverage. We explain how the oscillations between choreographic leadership and member influence and between digital media horizontalism and elite media-centric work constitute the space of interdependencies in which 38 Degrees acts. These delicately balanced relations can quickly dissolve and be replaced by simpler relations of dependence on professional media. Yet despite its fragility, we theorise about how 38 Degrees may boost individuals’ political efficacy, irrespective of the outcome of individual campaigns. Our conceptual framework can be used to guide research on similar movements

‘Shape-Up’, a Modified Cognitive-Behavioural Community Programme for Weight Management: Real-World Evaluation as an Approach for Delivering Public Health Goals

Obesity is widespread, with serious health consequences; addressing it requires considerable effort at a public health level, incorporating prevention and management along with policies to support implementation. Behavioural weight-management programmes are widely used by public health bodies to address overweight and obesity. Shape-Up is an evidence-based programme combining a structured behavioural intervention (targeting nutrition and physical activity behaviours) within a peer-learning framework. This study was a service-evaluation of Shape-Up, as delivered in Rotherham by a local leisure provider, and included a secondary analysis of data collected in the community by service providers. The RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) framework was used to explore programme effectiveness, implementation, and whom it reached. A total of 141 participants were included. Compared to local demographics, participants were older, at 48.9 (SD 14.47) years, with a lower employment rate (41% employed) and greater proportion female (67% female). Mean BMI was 38.0 (SD 7.54) kg/m2. Mean weight-change between baseline and endpoint (12 weeks, 10 group sessions) was −4.4 (SD 3.38) kg, and degree of weight change was associated with session attendance (F (9, 131) = 6.356, p < 0.0005). There were positive effects on participants’ weight, health-related behaviours, and quality of life. The intervention content (including the focus of nutritional recommendations) and structure were adapted during implementation to better suit national guidelines and local population needs. RE-AIM was found to be a useful framework for evaluating and adapting an existing evidence-based weight management programme in line with local population needs. This could be a more cost-effective approach, compared to developing new programmes, for delivering public health goals relating to obesity, nutrition, and physical activity

Use and evaluation of assistive technologies for upper limb function in tetraplegia

Context More than half of all spinal cord injuries (SCI) occur at the cervical level leading to loss of upper limb function, restricted activity and reduced independence. Several technologies have been developed to assist with upper limb functions in the SCI population. Objective There is no clear clinical consensus on the effectiveness of the current assistive technologies for the cervical SCI population, hence this study reviews the literature in the years between 1999 and 2019. Methods A systematic review was performed on the state-of-the-art assistive technology that supports and improves the function of impaired upper limbs in cervical SCI populations. Combinations of terms, covering assistive technology, SCI, and upper limb, were used in the search, which resulted in a total of 1770 articles. Data extractions were performed on the selected studies which involved summarizing details on the assistive technologies, characteristics of study participants, outcome measures, and improved upper limb functions when using the device. Results A total of 24 articles were found and grouped into five categories, including neuroprostheses (invasive and non-invasive), orthotic devices, hybrid systems, robots, and arm supports. Only a few selected studies comprehensively reported characteristics of the participants. There was a wide range of outcome measures and all studies reported improvements in upper limb function with the devices. Conclusions This study highlighted that assistive technologies can improve functions of the upper limbs in SCI patients. It was challenging to draw generalizable conclusions because of factors, such as heterogeneity of recruited participants, a wide range of outcome measures, and the different technologies employed

Flight of the dragonflies and damselflies

This work is a synthesis of our current understanding of the mechanics, aerodynamics and visually mediated control of dragonfly and damselfly flight, with the addition of new experimental and computational data in several key areas. These are: the diversity of dragonfly wing morphologies, the aerodynamics of gliding flight, force generation in flapping flight, aerodynamic efficiency, comparative flight performance and pursuit strategies during predatory and territorial flights. New data are set in context by brief reviews covering anatomy at several scales, insect aerodynamics, neuromechanics and behaviour. We achieve a new perspective by means of a diverse range of techniques, including laser-line mapping of wing topographies, computational fluid dynamics simulations of finely detailed wing geometries, quantitative imaging using particle image velocimetry of on-wing and wake flow patterns, classical aerodynamic theory, photography in the field, infrared motion capture and multi-camera optical tracking of free flight trajectories in laboratory environments. Our comprehensive approach enables a novel synthesis of datasets and subfields that integrates many aspects of flight from the neurobiology of the compound eye, through the aeromechanical interface with the surrounding fluid, to flight performance under cruising and higher-energy behavioural modes

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention

Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter