DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

Cognitive Analytic Therapy in People with Learning Disability: An investigation into the common reciprocal roles found within this client group

Developments over the last twenty years have shown that, contrary to previous opinion, people with learning disabilities can benefit from psychotherapy (Sinason 1992; Kroese, Dagnan & Loumidia, 1997). Cognitive Analytic Therapy (CAT) has been adapted for use with a learning disability population (Ryle 2002). CAT collaboratively examines the Reciprocal Roles (RRs) a client plays in relationships. These are impacted by clients’ experiences of the world. The aim of this research is to identify which RRs may become apparent in working with people with learning disabilities. The therapy notes of participants (n=16) who had undergone CAT were examined and analysed using content analysis. Twenty-two different RRs were found. Four common Reciprocal Roles and two common idealised Reciprocal Roles were identified. Other observations about the data are presented. The limitations and clinical implications of the study are discussed

Semisimple types for p -adic classical groups

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UK Biobank Urban Morphometric Platform (UKBUMP): a nationwide resource for evidence-based healthy city planning and public health interventions

The built environment (BE) has emerged as one of the ‘first causes’ of chronic disease, capable of explaining its socio-spatial variation. There is an increasing need for objective, detailed and precise measurements of attributes of BE that may influence our lifestyle, behaviour and hence physical and mental health. In this paper, we report the UK Biobank Urban Morphometric Platform (UKBUMP), the first ever very large sample size high resolution spatial database of urban morphological metrics (morphometrics), being developed for half-a-million participants of the UK Biobank Prospective study spatially distributed across 22 UK cities. Large-scale objective assessment of the BE was conducted employing state-of-the-art spatial and network analyses upon multiple national-level spatial data-sets. Prospective large-scale objective assessment of the BE enables the development of BE-health modelling studies that have the potential to identify causal pathways from specific attributes of the BE to various complex chronic health outcomes as well as well-being. The UKBUMP will act as a national resource, providing a platform for evidence-based healthy city planning and interventions for the first half of the twenty-first century.postprin

Morphometric analysis of the built environment in UL Biobank: Data analyses and specification manual

UK Biobank Built Environment Project - UKB WalesAvailable at: http://biobank.ctsu.ox.ac.uk/showcase/docs/ard-1195_UKBBuiltEnvWales.pd

Exploring associations between urban green, built environment configuration and walking: results from the Greater London boroughs

The Conference abstracts' website is located at https://www.icuh2014.com/Charter 3. Urban Planning and Architecture - Session title: Small are research for improving urban health - Ref: 621 OralIn recent years, lack of requisite physical activity has been identified as a key determinant of obesity and associated chronic diseases. In this paper, we examine the associations between objectively measured urban green and walking behaviour and how such associations are mediated by built environment configuration and street-level physical accessibility. The dwelling locations of the respondents of London Travel Demand Survey were geocoded and individual walking behaviour was extracted from the travel diary. The UK Map data was employed to calculate accessibility to urban green; expressed in terms of density of natural green, agricultural and anthropogenic green as well as street trees within defined buffers. A 0.5 metre resolution normalized difference vegetation index was employed to operationalize the degree of greenness. A network model of street-level physical accessibility was developed using spatial Domain Network Analysis (sDNA). A two-part multi-level regression model was employed with individuals nested within census-defined lower super output areas. The results show a significant influence of both urban green and street-level accessibility highlighting the need for targeted intervention strategies in the activity-friendly planning and design of urban built environment.postprin

Time to revise our dialogue : how flat is the paediatric flatfoot?

A recent systematic review of measures of foot development used the medial longitudinal arch profile as its primary indicator of development. A comparative analysis of existing studies was undertaken. This work confirmed changes with arch profile were age-dependent, although the age at which foot development ceased remains unknown. This work also highlighted the abundance of clinical measures used in existing research and outlined the challenges with drawing consensus from available data. There is a clear need to move this debate forward and, to do so, it is essential that scientific and clinical communities unite. It is time to abandon ill-defined measures of foot position, look beyond the medial longitudinal arch as a sole parameter of foot development and re-focus our perspective(s) on the paediatric foot in order to make advances with clinical practice and research

Stochastic generation of complex crystal structures combining group and graph theory with application to carbon

A method is introduced to stochastically generate crystal structures with defined structural characteristics. Reasonable quotient graphs for symmetric crystals are constructed using a random strategy combined with space group and graph theory. Our algorithm enables the search for large-size and complex crystal structures with a specified connectivity, such as three-fold sp2 carbons, four-fold sp3 carbons, as well as mixed sp2-sp3 carbons. To demonstrate the method we randomly construct initial structures adhering to space groups from No.75 to No.230 and a range of lattice constants, and we identify 281 new sp3 carbon crystals. First-principles optimization of these structures show that most of them are dynamically and mechanically stable and are energetically comparable to those previously proposed. Some of the new structures can be considered as candidates to explain the experimental cold compression of graphite