271 research outputs found

    RNA dysregulation in models of frontotemporal dementia and amyotrophic lateral sclerosis

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    Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) are two rare but devastating neurodegenerative diseases that share pathological features and genetic factors. A central question in both diseases is the role of the RNA-binding proteins transactive response DNA-binding protein 43kDa (TDP-43) and fused in sarcoma (FUS). These proteins play a vital role in RNA regulation in all cells but in diseased neurons they alter their cellular localisation to form potentially pathogenic aggregates. This process can be linked to rare genetic mutations in the TARDBP and FUS genes, although most cases of ALS and FTD have no known genetic cause. My work uses the revolutionary technology of RNA sequencing to measure and compare gene expression and RNA splicing in different cellular and animal models of sporadic and genetic disease. Here I present the results of four studies that investigate the biology of TDP-43 and FUS, assessing both their normal cellular roles and the impact of rare disease-causing mutations. In these projects I analyse RNA sequencing data to discover novel gene expression and RNA splicing phenomena. This includes the repression of cryptic splicing by TDP-43 but not FUS, the progressive downregulation of mitochondrial and ribosomal transcripts in a mouse model of FUS ALS, a gain of splicing function by TDP-43 mutations affecting constitutive exon splicing, and widespread changes in intron retention caused by FUS knockout or aggressive FUS mutations. I also discover a novel mechanism for how FUS might regulate its own translation. This work expands on what is currently known about the roles in RNA regulation for TDP- 43 and FUS and provides new avenues for understanding both the causes and progression of ALS and FTD

    Indiana Students Deserve High-Rated School Libraries

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    According to William Bainbridge, president of School Match, a firm that helps individuals and corporations evaluate 15,892 public school systems and 14,855 private schools; the level of expenditures for library and media services has the highest correlation with student achievement (New Jersey School Board Association Newsletter, 1995). Keith Curry Lance (2004) of the Colorado State Library found that schools with higher rated libraries have 10 to 18 percent better test scores than schools with lower rated libraries

    Special Educators and Mathematics Phobia: An Initial Qualitative Investigation

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    Special educators are uniquely challenged to be content experts in all curricular areas, including mathematics, since students in their case loads may require academic instruction in any area. However, special educators with math phobia may be limited in their ability to provide effective instruction to their students with mathematical deficits and/or needs, and may experience additional challenges in their professional and personal lives. This qualitative study sought to better understand the nature of math phobia in two special educators through extensive interviews, journaling, and observations in math experiences, with a number of primary themes identified. Several potential resolutions for the issues emerging from math phobia in special educators are identified and discussed

    Photographic Study of Combustion in a Rocket Engine I : Variation in Combustion of Liquid Oxygen and Gasoline with Seven Methods of Propellant Injection

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    Motion pictures at camera speeds up to 3000 frames per second were taken of the combustion of liquid oxygen and gasoline in a 100-pound-thrust rocket engine. The engine consisted of thin contour and injection plates clamped between two clear plastic sheets forming a two-dimensional engine with a view of the entire combustion chamber and nozzle. A photographic investigation was made of the effect of seven methods of propellant injection on the uniformity of combustion. From the photographs, it was found that the flame front extended almost to the faces of the injectors with most of the injection methods, all the injection systems resulted in a considerable nonuniformity of combustion, and luminosity rapidly decreased in the divergent part of the nozzle. Pressure vibration records indicated combustion vibrations that approximately corresponded to the resonant frequencies of the length and the thickness of the chamber. The combustion temperature divided by the molecular weight of the combustion gases as determined from the combustion photographs was about 50 to 70 percent of the theoretical value

    Mentors Increasing Special Education Retention

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    Lack of effective professional mentoring and minimal ongoing support programs have been suggested as two primary contributors to the chronic shortages of special education teachers. Few programs have been designed to address these specific causes. In this article we describe TATERS, a partnership between a university special educator preparation program, a state Department of Education, and district level administrations designed to (a) develop effective mentoring systems, and (b) strengthen training and recruitment of preservice and new special education teachers, especially in rural areas
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