Spinocerebellar Ataxia 8 (SCA8) appears unique among triplet repeat expansion-induced neurodegenerative diseases because the predicted gene product is a noncoding RNA. Little is currently known about the normal function of SCA8 in neuronal survival or how repeat expansion contributes to neurodegeneration. To investigate the molecular context in which SCA8 operates, we have expressed the human S...

Euglenoid flagellates have striped surface structures comprising pellicles, which allow the cell shape to vary from rigid to flexible during the characteristic movement of the flagellates. In Euglena gracilis, the pellicular strip membranes are covered with paracrystalline arrays of a major integral membrane protein, IP39, a putative four-membrane-spanning protein with the conserved sequence mo...

Tau pathology in Alzheimer's disease is intimately linked to the deposition of proteinacious filaments, which akin to infectious prions, have been proposed to spread via seeded conversion. Here we use double electron-electron resonance (DEER) spectroscopy in combination with extensive computational analysis to show that filaments of three- (3R) and four-repeat (4R) tau are conformationally dist...

Transmissible spongiform encephalopathies often are caused by peripheral uptake of infectious prions, and the peripheral nervous system is involved in prion spread to the brain. Although the cellular prion protein is subjected to fast axonal transport, the mechanism of intranerval transport of infectious prions is unclear. Here we administered prions intranervally to transgenic mice overexpress...

OBJECTIVE Although suicidal behavior is a major public health concern, understanding of individually sensitive suicide risk mechanisms is limited. In this study, the authors investigated, for the first time, the utility of defeat and entrapment in predicting repeat suicidal behavior in a sample of suicide attempters. METHOD Seventy patients hospitalized after a suicide attempt completed a ran...

BACKGROUND Framingham risk equations are widely used to predict cardiovascular disease based on health information from a single time point. Little is known regarding use of information from repeat risk assessments and temporal change in estimated cardiovascular risk for prediction of future cardiovascular events. This study was aimed to compare the discrimination and risk reclassification of a...

In Alzheimer's disease and frontotemporal dementias, the microtubule-associated protein Tau forms intracellular paired helical filaments. The filaments can form not only by the full-length human Tau protein, but also by the three repeated (K19) or four repeated (K18) Tau segments. However, of interest, experimentally, K19 can seed K18, but not vice versa. To obtain insight into the cross-seedin...

We have investigated a method to individualize the planning target volume (PTV) for deformable targets in radiotherapy by combining a computer tomography (CT) scan with multiple cone beam (CB)CT scans. All combinations of the CT and up to five initial CBCTs were considered. To exclude translational motion, the clinical target volumes (CTVs) in the CBCTs were matched to the CTV in the CT. PTVs i...

Molecular diagnosis of von Willebrand disease (VWD) has been hampered by the large size and complex genomic characteristics of the gene involved. For this reason, indirect methods using intragenic polymorphic markers described along the von Willebrand factor (VWF) gene are valuable tools for gene monitoring and linkage analysis. Several studies have demonstrated the four commonly utilized short...