Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening

Background: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics an

How Australian and New Zealand schools of optometry prepare students for culturally competent practice

Background: This study is an investigation of how Australian and New Zealand schools of optometry prepare students for culturally competent practice. The aims are: (1) to review how optometric courses and educators teach and prepare their students to work with culturally diverse patients; and (2) to determine the demographic characteristics of current optometric students and obtain their views on cultural diversity. Methods: All Australian and New Zealand schools of optometry were invited to participate in the study. Data were collected with two surveys: a curriculum survey about the content of the optometric courses in relation to cultural competency issues and a survey for second year optometry students containing questions in relation to cultural awareness, cultural sensitivity and attitudes to cultural diversity. Results: Four schools of optometry participated in the curriculum survey (Deakin University, Flinders University, University of Melbourne and University of New South Wales). Sixty-three students (22.3 per cent) from these four schools as well as the University of Auckland participated in the student survey. Cultural competency training was reported to be included in the curriculum of some schools, to varying degrees in terms of structure, content, teaching method and hours of teaching. Among second year optometry students across Australia and New Zealand, training in cultural diversity issues was the strongest predictor of cultural awareness and sensitivity after adjusting for school, age, gender, country of birth and language other than English. Conclusion: This study provides some evidence that previous cultural competency-related training is associated with better cultural awareness and sensitivity among optometric students. The variable approaches to cultural competency training reported by the schools of optometry participating in the study suggest that there may be opportunity for further development in all schools to consider best practice training in cultural competency. © 2014 Optometrists Association Australia

A comparative study of ovarian follicular dynamics and IGF-1 concentrations during an oestrus cycle in two genotypes of lactating Holstein-Friesian cows, offered pasture or a total mixed ration

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