Cell-Type Specific Translational Profiling in Huntington\u27s Disease Mouse Models

Medium spiny neurons (MSNs) are among the most vulnerable cell populations in Huntington’s Disease (HD). Within this population, striatopallidal MSNs are more vulnerable than striatonigral MSNs, which may explain the typical progression in HD of chorea to hypokinesis. The biological basis for this differential vulnerability is unknown, although differences in transcriptional dysfunction caused by mutant huntingtin (mhtt) have been proposed as a possible mechanism. In order to determine the differences in gene expression caused by mhtt in these two populations, we selectively isolated translated mRNAs from striatopallidal and striatonigral MSNs in the R6-2 and YAC128 HD mouse models at pre- and post-symptomatic time points using the BACTRAP technique (Heiman et al, 2008). We re-characterized the behavioral phenotype of the HD model mice on the D1 and D2 TRAP backgrounds and found many changes in the translated mRNA profiles of these two classes of medium spiny neurons, including known changes in the literature as well as novel pathways. One novel pathway was sphingosine-1-phosphate (S1P) signaling. Because the S1P-receptor G-protein coupled receptor 6 (GPR6) is enriched in striatopallidal cells, we hypothesized that changes in this pathway might play a role in striatopallidal medium spiny neuron vulnerability. Using mass spectrometry, we have shown that S1P levels, as well as other complex sphingolipid species, are decreased in the striatum of R6-2 mice early in disease progression. We have preliminary evidence to suggest Sphk2 and Sgpl1, the enzymes responsible for the production and degradation of S1P, are altered in HD mouse models in patterns that might explain the changes in S1P levels. We have shown that S1P can have pro-survival effects in an in vitro model of striatal origin. Together, these results implicate alterations in S1P signaling in the pathogenesis of Huntington’s Disease and offer an approach for moving from clinical observations of a disease toward the beginning of a mechanistic understanding of the underlying causes of specific cell vulnerability in other diseases

Toward the total synthesis of spirastrellolide A. Part 3: Intelligence gathering and preparation of a ring-expanded analogue

Different methods for the formation of the C.25–C.26 bond of spirastrellolide A (1) are evaluated that might qualify for the end game of the projected total synthesis, with emphasis on metathetic ways to forge the macrocyclic frame

Measurement of Carotid Plaque Volume by 3-Dimensional Ultrasound

Background and Purpose-Measurement of carotid plaque volume and its progression are important tools for research and patient management. In this study, we investigate the observer variability in the measurement of plaque volume as determined by 3-dimensional (3D) ultrasound (US). We also investigate the effect of interslice distances (ISD) and repeated 3D US scans on measurement variability. Materials and Methods-Forty 3D US patient images of plaques (range, 37.43 to 604.1 mm3) were measured by manual planimetry. We applied ANOVA to determine plaque volume measurement variability and reliability. Plaque volumes were measured with 9 ISDs to determine the effect of ISD on measurement variability. Additional plaque volumes were also measured from multiple 3D US scans to investigate repeated scan acquisition variability. Results-Intraobserver and interobserver measurement reliabilities were 94% and 93.2%, respectively. Plaque volume measurement variability decreased with increasing plaque volume (range, 27.1% to 2.2%). Measurement precision was constant for ISDs between 1.0 and 3.0 mm, whereas plaque volume measurement variability increased with ISD. Repeated 3D US scan measurements were not different from single-scan measurements (P=0.867). Conclusions-The coefficient of variation in the measurement of plaque volume decreased with plaque size. The volumetric change that must be observed to establish with 95% confidence that a plaque has undergone change is ≈20% to 35% for plaques \u3c100 mm3 and ≈10% to 20% for plaques \u3e100 mm3. Measurement precision was unchanged for ISDs \u3e3.0 mm, whereas measurement variability increased with ISD. Repeated 3D US scans did not affect plaque volume measurement variability

Weed Control for Reduced Tillage Systems

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EC58-123 Questions and Answers about Stubble Mulching

Extension Circular 58-123 provides questions and answers about Stubble Mulch farming

EC58-123 Questions and Answers about Stubble Mulching

Extension Circular 58-123 provides questions and answers about Stubble Mulch farming

Date of Planting Studies of Winter Wheat and Winter Barley in Relation to Root and Crown Rot Grain Yields and Quality

This study was undertaken to determine the nature of root and crown rot of wheat and to ascertain the proper time to plant winter wheat so as to conserve moisture, minimize root and crown rot and thereby maximize yield. Studies conducted for 15 years at several locations in western Nebraska reveal that planting date is a significant factor for higher yields, particularly in certain years

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening.We thank the National Institutes of Health KU Chemical Methodologies and Library Development Center of Excellence (P50 GM069663) for funding. We are indebted to Dr. Conrad Santini and Ben Neuenswander for help in library production and purification

Analysis of carotid lumen surface morphology using three-dimensional ultrasound imaging

Carotid plaque surface irregularity and ulcerations play an important role in the risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular surface morphology, exposes thrombogenic materials to the bloodstream, possibly leading to life- or brain-threatening thrombosis and embolization. Therefore, the quantification of plaque surface irregularity is important to identify high-risk plaques that would likely lead to vascular events. Although a number of studies have characterized plaque surface irregularity using subjective classification schemes with two or more categories, only a few have quantified surface irregularity using an objective and continuous quantity, such as Gaussian or mean curvature. In this work, our goal was to use both Gaussian and mean curvatures for identifying ulcers from 3D carotid ultrasound (US) images of human subjects. Before performing experiments using patient data, we verified the numerical accuracy of the surface curvature computation method using discrete spheres and tori with different sampling intervals. We also showed that three ulcers of the vascular phantom with 2 mm, 3 mm and 4 mm diameters were associated with high Gaussian and mean curvatures, and thus, were easily detected. Finally, we demonstrated the application of the proposed method for detecting ulcers on luminal surfaces, which were segmented from the 3D US images acquired for two human subjects

Quantification of carotid vessel wall and plaque thickness change using 3D ultrasound images

Quantitative measurements of carotid plaque burden progression or regression are important in monitoring patients and in evaluation of new treatment options. 3D ultrasound (US) has been used to monitor the progression or regression of carotid artery plaques. This paper reports on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US. The technique used is evaluated using manual segmentations of the arterial wall and lumen from 3D US images acquired in two imaging sessions. To reduce the effect of segmentation variability, segmentation was performed five times each for the wall and lumen. The mean wall and lumen surfaces, computed from this set of five segmentations, were matched on a point-by-point basis, and the distance between each pair of corresponding points served as an estimate of the combined thickness of the plaque, intima, and media (vessel-wall-plus-plaque thickness or VWT). The VWT maps associated with the first and the second US images were compared and the differences of VWT were obtained at each vertex. The 3D VWT and VWT-Change maps may provide important information for evaluating the location of plaque progression in relation to the localized disturbances of flow pattern, such as oscillatory shear, and regression in response to medical treatments