Noncoding Centromeric RNA Expression Impairs Chromosome Stability in Human and Murine Stem Cells

We analyzed the effect of transcribed noncoding RNA centromeric satellites on chromosome segregation in normal human and murine stem and fibrosarcoma cells. The overexpression of different centromeric alphoid DNAs in all cell lines induced a marked increase in chromosome mis-segregation in anaphase. Overexpression of centromeric mouse minor satellite also increased chromosome instability in the murine stem but not in human cells. Analysis of chromosome segregation in vivo showed disturbances in the mitotic progression, which was frequently unresolved. Live cell imaging revealed that overexpression of centromeric satellites resulted in several different chromosomal morphological errors in the cell nuclei. Our findings correlated with other reports that several centromeric noncoding RNAs are detected in different carcinoma cells and their expression resulted in segregation errors. Our study furnishes further insights into a novel source of genomic instability in human and murine cells. It has recently been shown that noncoding centromeric RNAs are present in some form of cancer, and thus, overexpression of several types of centromeric noncoding RNAs may be useful as a specific maker for neoplastic cells

Multigene human artificial chromosome vector delivery with herpes simplex virus 1 amplicons

Gene expression studies and gene therapy require efficient gene delivery into cells. Different technologies by viral and non-viral mechanisms have been used for gene delivery into cells. Small gene vectors transfer across the cell membrane with a relatively high efficiency, but not large genes or entire loci spanning several kilobases, which do not remain intact following introduction. Previously, we developed an efficient delivery system based on herpes virus simplex type 1 (HSV-1) amplicons to transfer large fragments of DNA incorporated in human artificial chromosome (HAC) vectors into the nucleus of human cells. The HSV-1 amplicon lacks the signals for cleavage and replication of its own genome, yet each amplicon has the capacity to incorporate up to 150 kb of exogenous DNA. In this study, we investigated whether the capacity of gene delivery could be increased by simultaneously introducing multiple HSV-1 modified amplicons carrying a gene expressing HAC vector into cells with the aim of generating a single artificial chromosome containing the desired genes. Following co-transduction of two HSV-1 HAC amplicons, artificial chromosomes were successfully generated containing the introduced genes, which were appropriately expressed in different human cell types

Effects of arm weight support training to promote recovery of upper limb function for subacute patients after stroke with different levels of arm impairments

2015-2016 > Academic research: refereed > Publication in refereed journalVersion of RecordSelf-fundedPublishe

Production of Paralytic Shellfish Toxins (PSTs) in toxic alexandrium catenella is intertwined with photosynthesis and energy production

202010 bcmaVersion of RecordPublishe

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Novel approach for anterior chamber angle analysis: Anterior Chamber Angle Detection with Edge Measurement and Identification Algorithm (ACADEMIA)

Objective: To describe a novel approach to measuring anterior chamber angle dimensions and configurations. Methods: Sixty-nine images were selected randomly from the ultrasound biomicroscopic image database to develop the algorithm. Thirty images were selected for further analyses. The value of each pixel of the 8-bit grayscale ultrasound biomicroscopic images was quantized into 0 (black) or 1 (white), and the edge points outlining the angle were detected and fitted with straight lines. The dimensions and profiles of anterior chamber angles were then measured. Results: The algorithm failed to identify the edge points correctly in 8 (11.6%) of 69 images because of strong background noise. Three basic types of angle configuration were identified based on the derived angle profiles: constant, increasing, and decreasing, which corresponded to flat, bowed forward, and bowed backward iris contours, respectively. The angle measurements demonstrated high correlation with trabecular-iris angle and angle opening distance 500 (calculated as the distance from the corneal endothelium to the anterior iris surface perpendicular to a line drawn at 500 μm from the scleral spur). The strongest association was found between the averaged angle derived from the angle profile and the angle opening distance 500 (r=0.91). Conclusion: The proposed algorithm has high correlations with angle opening distance and trabecular-iris angle with the added advantages of being fully automated, reproducible, and able to capture the characteristic angle configurations. However, good-quality ultrasound biomicroscopic images with high signal-to-noise ratio are required to identify the edge points correctly. ©2006 American Medical Association. All rights reserved.link_to_subscribed_fulltex