PAX6 mutations: genotype-phenotype correlations

BACKGROUND: The PAX6 protein is a highly conserved transcriptional regulator that is important for normal ocular and neural development. In humans, heterozygous mutations of the PAX6 gene cause aniridia (absence of the iris) and related developmental eye diseases. PAX6 mutations are archived in the Human PAX6 Allelic Variant Database, which currently contains 309 records, 286 of which are mutations in patients with eye malformations. RESULTS: We examined the records in the Human PAX6 Allelic Variant Database and documented the frequency of different mutation types, the phenotypes associated with different mutation types, the contribution of CpG transitions to the PAX6 mutation spectrum, and the distribution of chain-terminating mutations in the open reading frame. Mutations that introduce a premature termination codon into the open reading frame are predominantly associated with aniridia; in contrast, non-aniridia phenotypes are typically associated with missense mutations. Four CpG dinucleotides in exons 8, 9, 10 and 11 are major mutation hotspots, and transitions at these CpG's account for over half of all nonsense mutations in the database. Truncating mutations are distributed throughout the PAX6 coding region, except for the last half of exon 12 and the coding part of exon 13, where they are completely absent. The absence of truncating mutations in the 3' part of the coding region is statistically significant and is consistent with the idea that nonsense-mediated decay acts on PAX6 mutant alleles. CONCLUSION: The PAX6 Allelic Variant Database is a valuable resource for studying genotype-phenotype correlations. The consistent association of truncating mutations with the aniridia phenotype, and the distribution of truncating mutations in the PAX6 open reading frame, suggests that nonsense-mediated decay acts on PAX6 mutant alleles

Comics and Illustration from the Written; The Conversion of a Story from Prose to Graphic Depiction.

This is a thesis that details the process of writing a short 30 page novel, and then converting the subsequent story into a graphic format via illustrations and into a comic book layout. The story itself deals in reworking our learned assumptions of good and evil, specifically in the supernatural and human possibility for both. The comic book format is an exploration of my reader’s different responses to the written and the graphic

#MeToo Movement: Solutions

Sexual assault and sexual harassment is a prevalent issue that affects women at disproportionate rates on college campuses, in the workplace and in society in general. The #MeToo movement aims to bring discussion around these issues, hold sexual predators accountable for their actions, and provide a support system for survivors of sexual assault and harassment. #MeToo Movement: Solutions analyzes the scope of the problem in the United States, famous cases surrounding sexual assault, and the different solutions colleges, society in general, and legislation have put in place to combat this issue. The #MeToo Movement has made a lot of headway in the loss of many jobs of men in powerful positions and the movement still continues to bring awareness, voice many survivor’s stories and create change in regard to sexual violence

A College Woman\u27s Guide to Self-Discovery

College students often ask big questions: Where do I fit in? What gives my life meaning? How can I make a difference? And where do I begin? Women at this age are on a journey of self-discovery, exploring these and other complex, life-changing issues that don\u27t have easy answers. For this master\u27s project, I created a prototype of a book for college women and recent graduates who are on a journey toward authentic living. It is about helping them identify their unique strengths, values, and abilities; discover and harness their passions; and develop a creative mindset that will help them navigate the unfamiliar, yet exciting places their lives may lead. While it does not offer answers to life\u27s big questions, it does provide thought-provoking essays, journaling prompts, and creative exercises to help them explore these questions on their own. It does so from a uniquely female perspective, with stories and advice from women who have passed this way before them

Use of the score test as a goodness-of-fit measure of the covariance structure in genetic analysis of longitudinal data

Model selection is an essential issue in longitudinal data analysis since many different models have been proposed to fit the covariance structure. The likelihood criterion is commonly used and allows to compare the fit of alternative models. Its value does not reflect, however, the potential improvement that can still be reached in fitting the data unless a reference model with the actual covariance structure is available. The score test approach does not require the knowledge of a reference model, and the score statistic has a meaningful interpretation in itself as a goodness-of-fit measure. The aim of this paper was to show how the score statistic may be separated into the genetic and environmental parts, which is difficult with the likelihood criterion, and how it can be used to check parametric assumptions made on variance and correlation parameters. Selection of models for genetic analysis was applied to a dairy cattle example for milk production

A radio Search for high redshift HI absorption

Ground based optical observations have yielded considerable information on the statistics of damped-lyman alpha systems. In particular these systems are known to be the dominant repository of the observed neutral gas at high redshift. However, particularly at high redshift, there is the possibility that optical observations could be biased due to the exclusion of damped-lyman alpha systems that contain moderate to significant amounts of dust. Independent observational constraints on the neutral hydrogen content at high redshifts and the amount of dust in high redshift systems can be obtained from a radio search against the bright lobes of distant radio galaxies (which is less affected by the presence of dust in foreground damped-lyman alpha systems). We describe here a pilot radio survey along the line of sight to a small sample of high redshift radio galaxies, and also present some preliminary results. The survey uses a novel observing mode at the WSRT which enables one to make sensitive searches of a large redshift interval in a modest amount of telescope time.Comment: A version with figures is available at http://www.nfra.nl/~chengalu/ To appear in "Cold Gas at High Redshift", Eds. M.Bremer et al. (Kluwer, Dordrecht

Research note: Urban street tree density and antidepressant prescription rates—A cross-sectional study in London, UK

This is the author’s version of a work that was accepted for publication in Landscape and Urban Planning. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published at doi:10.1016/j.landurbplan.2014.12.005.Abstract: Growing evidence suggests an association between access to urban greenspace and mental health and wellbeing. Street trees may be an important facet of everyday exposure to nature in urban environments, but there is little evidence regarding their role in influencing population mental health. In this brief report, we raise the issue of street trees in the nature-health nexus, and use secondary data sources to examine the association between the density of street trees (trees/km street) in London boroughs and rates of antidepressant prescribing. After adjustment for potential confounders, and allowing for unmeasured area-effects using Bayesian mixed effects models, we find an inverse association, with a decrease of 1.18 prescriptions per thousand population per unit increase in trees per km of street (95% credible interval 0.00, 2.45). This study suggests that street trees may be a positive urban asset to decrease the risk of negative mental health outcomes.European Regional Development Fund Programme 2007 to 2013 and European Social Fund Convergence Programme for Cornwall and the Isles of Scill