Polyglutamine Genes Interact to Modulate the Severity and Progression of Neurodegeneration in Drosophila

The expansion of polyglutamine tracts in a variety of proteins causes devastating, dominantly inherited neurodegenerative diseases, including six forms of spinal cerebellar ataxia (SCA). Although a polyglutamine expansion encoded in a single allele of each of the responsible genes is sufficient for the onset of each disease, clinical observations suggest that interactions between these genes may affect disease progression. In a screen for modifiers of neurodegeneration due to SCA3 in Drosophila, we isolated atx2, the fly ortholog of the human gene that causes a related ataxia, SCA2. We show that the normal activity of Ataxin-2 (Atx2) is critical for SCA3 degeneration and that Atx2 activity hastens the onset of nuclear inclusions associated with SCA3. These activities depend on a conserved protein interaction domain of Atx2, the PAM2 motif, which mediates binding of cytoplasmic poly(A)-binding protein (PABP). We show here that PABP also influences SCA3-associated neurodegeneration. These studies indicate that the toxicity of one polyglutamine disease protein can be dramatically modulated by the normal activity of another. We propose that functional links between these genes are critical to disease severity and progression, such that therapeutics for one disease may be applicable to others

The InterLACE study: design, data harmonization and characteristics across 20 studies on women's health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE

A cross-sectional study of the number and frequency of terms used to refer to knowledge translation in a body of health literature in 2006: a Tower of Babel?

<p/> <p>Background</p> <p>The study of implementing research findings into practice is rapidly growing and has acquired many competing names (<it>e.g</it>., dissemination, uptake, utilization, translation) and contributing disciplines. The use of multiple terms across disciplines pose barriers to communication and progress for applying research findings. We sought to establish an inventory of terms describing this field and how often authors use them in a collection of health literature published in 2006.</p> <p>Methods</p> <p>We refer to this field as knowledge translation (KT). Terms describing aspects of KT and their definitions were collected from literature, the internet, reports, textbooks, and contact with experts. We compiled a database of KT and other articles by reading 12 healthcare journals representing multiple disciplines. All articles published in these journals in 2006 were categorized as being KT or not. The KT articles (all KT) were further categorized, if possible, for whether they described KT projects or implementations (KT application articles), or presented the theoretical basis, models, tools, methods, or techniques of KT (KT theory articles). Accuracy was checked using duplicate reading. Custom designed software determined how often KT terms were used in the titles and abstracts of articles categorized as being KT.</p> <p>Results</p> <p>A total of 2,603 articles were assessed, and 581 were identified as KT articles. Of these, 201 described KT applications, and 153 included KT theory. Of the 100 KT terms collected, 46 were used by the authors in the titles or abstracts of articles categorized as being KT. For all 581 KT articles, eight terms or term variations used by authors were highly discriminating for separating KT and non-KT articles (p < 0.001): implementation, adoption, quality improvement, dissemination, complex intervention (with multiple endings), implementation (within three words of) research, and complex intervention. More KT terms were associated with KT application articles (n = 13) and KT theory articles (n = 18).</p> <p>Conclusions</p> <p>We collected 100 terms describing KT research. Authors used 46 of them in titles and abstracts of KT articles. Of these, approximately half discriminated between KT and non-KT articles. Thus, the need for consolidation and consistent use of fewer terms related to KT research is evident.</p

A broadly implementable research course in phage discovery and genomics for first-year undergraduate students

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students\u27 interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training

Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys

Abstract BACKGROUND: The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data. METHODS: Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes). CONCLUSIONS: The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

A Broadly Implementable Research Course in Phage Discovery and Genomics for First-Year Undergraduate Students

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students’ interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training