The use of β-cell transcription factors in engineering artificial β cells from non-pancreatic tissue

Type 1 diabetes results from the autoimmune destruction of the insulin-producing pancreatic beta (β) cells. Patients with type 1 diabetes control their blood glucose levels using several daily injections of exogenous insulin; however, this does not eliminate the long-term complications of hyperglycaemia. Currently, the only clinically viable treatments for type 1 diabetes are whole pancreas and islet transplantation. As a result, there is an urgent need to develop alternative therapies. Recently, cell and gene therapy have shown promise as a potential cure for type 1 diabetes through the genetic engineering of 'artificial' β cells to regulate blood glucose levels without adverse side effects and the need for immunosuppression. This review compares putative target cells and the use of pancreatic transcription factors for gene modification, with the ultimate goal of engineering a glucose-responsive 'artificial' β cell that mimics the function of pancreatic β cells, while avoiding autoimmune destruction

A new model of cosmogenic production of radiocarbon 14C in the atmosphere

We present the results of full new calculation of radiocarbon 14C production in the Earth atmosphere, using a numerical Monte-Carlo model. We provide, for the first time, a tabulated 14C yield function for the energy of primary cosmic ray particles ranging from 0.1 to 1000 GeV/nucleon. We have calculated the global production rate of 14C, which is 1.64 and 1.88 atoms/cm2/s for the modern time and for the pre-industrial epoch, respectively. This is close to the values obtained from the carbon cycle reservoir inventory. We argue that earlier models overestimated the global 14C production rate because of outdated spectra of cosmic ray heavier nuclei. The mean contribution of solar energetic particles to the global 14C is calculated as about 0.25% for the modern epoch. Our model provides a new tool to calculate the 14C production in the Earth's atmosphere, which can be applied, e.g., to reconstructions of solar activity in the past.Comment: Published in EPSL, 337, 114, 201

Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi.

BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen-activated protein (MAP) kinase pathway. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. Here we report frequent somatic mutations in the heterotrimeric G protein alpha-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the Ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention

Developing a comparative marine socio-economic framework for the European Atlantic Area

Availability and easy access to a wide range of natural and human-activity data on the oceans and coastal regions of Europe is the basis for strategic decision-making on coastal and marine policy. Strategies within Europe’s Integrated Maritime Policy, including the Maritime Strategy for the Atlantic Area, Blue Growth, Maritime Spatial Planning and Marine Data and Knowledge, require coherent and comparable socio-economic data across European countries. Similarly, the Marine Strategy Framework Directive requires member states to carry out economic and social analysis of their waters and the reformed Common Fisheries Policy includes a social dimension requiring socio-economic data. However, the availability of consistent, accessible marine socio-economic data for the European Atlantic Arc regions is limited. Ocean economy studies have been undertaken in some countries (for example, Ireland, France, and UK) but timescales and methodologies are not necessarily comparable. Marnet is an EU transnational co-operation project involving eight partners from five member states of the Atlantic Area (Ireland, Spain, UK, France and Portugal). Marnet has developed a methodology to collate comparable marine socio-economic data across the Atlantic regions. The comparative marine socio-economic information system developed by Marnet could provide a template for other European States to follow that could potentially facilitate the construction of a Europe-wide marine economic information system as envisaged under the EU Integrated Maritime Policy

Axonal Preservation in Deep Subcortical White Matter Lesions in the Ageing Brain

Cerebral white matters lesions (WML) are seen in 94% of the population aged 64 and over and are associated with cognitive decline and depression. We used immunohistochemistry and stereological methods on post mortem brain samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort to investigate the axonal density within deep subcortical lesions. There was no significant difference between the lesional and control white matter, therefore, we conclude that there is axonal preservation within these lesions that are characterized by demyelination

You’ll never walk alone: supportive social relations in a football and mental health project

Football can bring people together in acts of solidarity and togetherness. This spirit is most evocatively illustrated in the world renowned football anthem You’ll Never Walk Alone (YNWA). In this paper we argue that this spirit can be effectively harnessed in nursing and mental health care. We draw on data from qualitative interviews undertaken as part of evaluating a football and mental health project to explore the nature of supportive social relations therein. We use some of the lyrics from YNWA as metaphor to frame our thematic analysis. We are especially interested in the interactions between the group facilitators and group members, but also address aspects of peer support within the groups. A contrast is drawn between the flexible interpersonal boundaries and self-disclosure evident in the football initiative and the reported more distant relations with practitioners in mainstream mental health services. Findings suggest scope for utilising more collective, solidarity enhancing initiatives and attention to alliances and boundaries to maximise engagement and therapeutic benefits within routine practice

高効率線形送信法におけるPWM包絡線発生法の研究

電気通信大学200

Insulin trafficking in a glucose responsive engineered human liver cell line is regulated by the interaction of ATP-sensitive potassium channels and voltage- gated calcium channels

Type I diabetes is caused by the autoimmune destruction of pancreatic beta (â) cells [1]. Current treatment requires multiple daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate, the onset of diabetic complications, which greatly reduce the quality and longevity of life for patients. Transplantation of pancreatic tissue as a treatment is restricted by the scarcity of donors and the requirement for lifelong immunosuppression to preserve the graft, which carries adverse side-effects. This is of particular concern as Type 1 diabetes predominantly affects children. Lack of glucose control could be overcome by genetically engineering "an artificial â-cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The donor cell type must be readily accessible and capable of being engineered to synthesise, process, store and secrete insulin under physiological conditions