Evidence of widespread degradation of gene control regions in hominid genomes

Although sequences containing regulatory elements located close to protein-coding genes are often only weakly conserved during evolution, comparisons of rodent genomes have implied that these sequences are subject to some selective constraints. Evolutionary conservation is particularly apparent upstream of coding sequences and in first introns, regions that are enriched for regulatory elements. By comparing the human and chimpanzee genomes, we show here that there is almost no evidence for conservation in these regions in hominids. Furthermore, we show that gene expression is diverging more rapidly in hominids than in murids per unit of neutral sequence divergence. By combining data on polymorphism levels in human noncoding DNA and the corresponding human¿chimpanzee divergence, we show that the proportion of adaptive substitutions in these regions in hominids is very low. It therefore seems likely that the lack of conservation and increased rate of gene expression divergence are caused by a reduction in the effectiveness of natural selection against deleterious mutations because of the low effective population sizes of hominids. This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees

Activity-regulated RNA editing in select neuronal subfields in hippocampus

RNA editing by adensosine deaminases is a widespread mechanism to alter genetic information in metazoa. In addition to modifications in non-coding regions, editing contributes to diversification of protein function, in analogy to alternative splicing. However, although splicing programs respond to external signals, facilitating fine tuning and homeostasis of cellular functions, a similar regulation has not been described for RNA editing. Here, we show that the AMPA receptor R/G editing site is dynamically regulated in the hippocampus in response to activity. These changes are bi-directional, reversible and correlate with levels of the editase Adar2. This regulation is observed in the CA1 hippocampal subfield but not in CA3 and is thus subfield/celltype-specific. Moreover, alternative splicing of the flip/flop cassette downstream of the R/G site is closely linked to the editing state, which is regulated by Ca(2+). Our data show that A-to-I RNA editing has the capacity to tune protein function in response to external stimuli

Evaluation of readability and accuracy of information leaflets in general practice for patients with asthma

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A war for principle? Shifting memories of the Union cause in Iowa, 1865-1916

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Are GPs under-investigating older patients presenting with symptoms of ovarian cancer? Observational study using General Practice Research Database

Background: Recent studies suggest that older patients in the United Kingdom are not benefiting as much from improvements in cancer treatments as their younger counterparts. We investigate whether this might be partly due to differential referral rates using ovarian cancer as an example. Methods: From the General Practice Research Database (GPRD), we identified all women aged 40–80 years on 1 June 2002 with a Read code for ovarian cancer between 1 June 2002 and 31 May 2007. Using these records, we compared the GPRD incidence of ovarian cancer with rates compiled from the UK cancer registries and investigated the relationship between age and coded investigations for suspected ovarian cancer. Results: The GPRD rates peaked earlier, at 70–74, and were lower than registry rates for nearly all ages particularly for patients over 59. The proportion investigated or referred by the GP decreased significantly with age and delays between first coded symptom and investigation showed a U-shaped distribution by age. Conclusions: GPs appear to be less likely to recognise and to refer patients presenting with ovarian cancer as they get older. If our findings extend to other cancers, lack of or delays in referral to secondary care may partly explain poor UK cancer mortality rates of older people

Bullying and school attendance: a case study of senior high school students in Ghana

This paper focuses on senior high school students and the ways that bullying affects their school attendance. Selected items from the 2008 Ghana Global School-based Student Health Survey are analysed first to explore the relationships between the duration and type of bullying and school attendance. Second, we investigate whether having emotional problems, in addition to being bullied, incrementally affects the relationship between bullying and school attendance. Third, we explore the mitigating influence of peer friendships on these relationships. In all cases we provide a gender analysis. The results show that bullying is associated with increased absenteeism for both boys and girls. The analysis of reported emotional problems, however, shows distinct gender differences. For boys, increases in emotional problems are not associated with increased absenteeism for those who are bullied. On the other hand, for girls emotional problems were strongly associated with absenteeism and more so for girls who had not reported being bullied. The third strand of our analysis also showed gender differences in which absenteeism associated with bullying was mitigated by the support of friends for boys but not to the same degree for girls, especially those girls who had reported being psychologically bullied. In addition to the threat to school access caused by bullying, the gender dimensions of the latter two sets of findings suggest a school environment in which peer friendship and emotional well-being are intertwined in complex ways. While there is little or no research within the Ghanaian context, supported by research from elsewhere, we suggest that peer friendships for girls may be comprised of more non-physical, social and verbal interaction within which it might be more difficult to pinpoint bullying. That peer interactions might include a mixture of support and bullying could explain why there is a strong influence on girls’ emotional well-being and hence their school attendance

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

John Rawls, 1921-2002: A chastened but not trivial liberalism

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Making it real: exploring the potential of Augmented Reality for teaching primary school science

The use of Augmented Reality (AR) in formal education could prove a key component in future learning environments that are richly populated with a blend of hardware and software applications. However, relatively little is known about the potential of this technology to support teaching and learning with groups of young children in the classroom. Analysis of teacher-child dialogue in a comparative study between use of an AR virtual mirror interface and more traditional science teaching methods for 10-year-old children, revealed that the children using AR were less engaged than those using traditional resources. We suggest four design requirements that need to be considered if AR is to be successfully adopted into classroom practice. These requirements are: flexible content that teachers can adapt to the needs of their children, guided exploration so learning opportunities can be maximised, in a limited time, and attention to the needs of institutional and curricular requirements