A study of the ultrastructure of Fragile-X-related proteins

Fragile-X-related proteins form a family implicated in RNA metabolism. Their sequence is composed of conserved N-terminal and central regions which contain Tudor and KH domains and of a divergent C-terminus with motifs rich in arginine and glycine residues. The most widely studied member of the family is probably FMRP (fragile X mental retardation protein), since absence or mutation of this protein in humans causes fragile X syndrome, the most common cause of inherited mental retardation. Understanding the structural properties of FMRP is essential for correlating it with its functions. The structures of isolated domains of FMRP have been reported, but nothing is yet known with regard to the spatial arrangement of the different modules, partly because of difficulties in producing both the full-length protein and its multidomain fragments in quantities, purities and monodispersity amenable for structural studies. In the present study, we describe how we have produced overlapping recombinant fragments of human FMRP and its paralogues which encompass the evolutionary conserved region. We have studied their behaviour in solution by complementary biochemical and biophysical techniques, identified the regions which promote self-association and determined their overall three-dimensional shape. The present study paves the way to further studies and rationalizes the existing knowledge on the self-association properties of these proteins

Circadian Rhythm-Dependent Alterations of Gene Expression in Drosophila Brain Lacking Fragile X Mental Retardation Protein

Fragile X syndrome is caused by the loss of the FMR1 gene product, fragile X mental retardation protein (FMRP). The loss of FMRP leads to altered circadian rhythm behaviors in both mouse and Drosophila; however, the molecular mechanism behind this phenomenon remains elusive. Here we performed a series of gene expression analyses, including of both mRNAs and microRNAs (miRNAs), and identified a number of mRNAs and miRNAs (miRNA-1 and miRNA-281) with circadian rhythm-dependent altered expression in dfmr1 mutant flies. Identification of these RNAs lays the foundation for future investigations of the molecular pathway(s) underlying the altered circadian rhythms associated with loss of dFmr1

Sketches of Liberia: comprising a brief account of the geography, climate, productions, and diseases, of the republic of Liberia.

Printed wrappers.Mode of access: Internet

Alternative Delivery Styles for Health Training in Rural Settings

Rural hospitals, unlike many other business/industries, lack the resources to educate/upgrade health cam technicians without outside assistance. This paper describes how a university, with an innovative, customized delivery system, was able to provide college level instruction at small, rural hospitals with minimal costs. Using this competency-based programme, all instruction was provided through video, slides/tapes, and programmed learning materials. Daily student supervision/assistance was provided by hospital training supervisors, who usually were full-time departmental supervisors with appropriate licensure. The educational institution provided instructors called Education Specialists who had appropriate healthcare licensure. They provided learning materials on a regular basis, and assessed student progress and program development at each cooperating rural hospital. Successes were measured by (a) the number of hospital employees who were upgraded to new skill levels and their job satisfaction; and (b) the number of semester hours generated for the educational institution

A nonsense mutation in FMR1 causing fragile X syndrome

Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is the expansion of a CGG repeat located in the 5′UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent. Only few patients with intragenic point mutations in FMR1 have been reported and, currently, routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including western blot and DNA sequence analysis of the FMR1 gene should be performed in patients with typical symptoms of fragile X syndrome in whom no CGG repeat expansion is detected