BCIT Citations Collection | BCIT Institutional Repository

BCIT Citations Collection

Pages

Schwann cells generated from neonatal skin-derived precursors or neonatal peripheral nerve improve functional recovery after acute transplantation into the partially injured cervical spinal cord of the rat
The transplantation of Schwann cells (SCs) holds considerable promise as a therapy for spinal cord injury, but the optimal source of these cells and the best timing for intervention remains debatable. Previously, we demonstrated that delayed transplantation of SCs generated from neonatal mouse skin-derived precursors (SKP-SCs) promoted repair and functional recovery in rats with thoracic contusions. Here, we conducted two experiments using neonatal rat cells and an incomplete cervical injury model to examine the efficacy of acute SKP-SC transplantation versus media control (Experiment 1) and versus nerve-derived SC or dermal fibroblast (Fibro) transplantation (Experiment 2). Despite limited graft survival, by 10 weeks after injury, rats that received SCs from either source showed improved functional recovery compared with media- or fibroblast-treated animals. Compared with media treatment, SKP-SC-transplanted rats showed enhanced rubrospinal tract (RST) sparing/plasticity in the gray matter (GM) rostral to injury, particularly in the absence of immunosuppression. The functional benefits of SC transplantations over fibroblast treatment correlated with the enhanced preservation of host tissue, reduced RST atrophy, and/or increased RST sparing/plasticity in the GM. In summary, our results indicate that: (1) early transplantation of neonatal SCs generated from skin or nerve promotes repair and functional recovery after incomplete cervical crush injury; (2) either of these cell types is preferable to Fibros for these purposes; and (3) age-matched SCs from these two sources do not differ in terms of their reparative effects or functional efficacy after transplantation into the injured cervical spinal cord., Peer-reviewed article, Published.Received March 17, 2014; revised March 18, 2015; accepted March 21, 2015.
Shaped 3D singular spectrum analysis for quantifying gene expression, with application to the early zebrafish embryo
Recent progress in microscopy technologies, biological markers, and automated processing methods is making possible the development of gene expression atlases at cellular-level resolution over whole embryos. Raw data on gene expression is usually very noisy. This noise comes from both experimental (technical/methodological) and true biological sources (from stochastic biochemical processes). In addition, the cells or nuclei being imaged are irregularly arranged in 3D space. This makes the processing, extraction, and study of expression signals and intrinsic biological noise a serious challenge for 3D data, requiring new computational approaches. Here, we present a new approach for studying gene expression in nuclei located in a thick layer around a spherical surface. The method includes depth equalization on the sphere, flattening, interpolation to a regular grid, pattern extraction by Shaped 3D singular spectrum analysis (SSA), and interpolation back to original nuclear positions. The approach is demonstrated on several examples of gene expression in the zebrafish egg (a model system in vertebrate development). The method is tested on several different data geometries (e.g., nuclear positions) and different forms of gene expression patterns. Fully 3D datasets for developmental gene expression are becoming increasingly available; we discuss the prospects of applying 3D-SSA to data processing and analysis in this growing field., Peer-reviewed article, Published. Received 8 February 2015; Accepted 1 May 2015.
Shaped singular spectrum analysis for quantifying gene expression, with application to the early drosophila embryo
In recent years, with the development of automated microscopy technologies, the volume and complexity of image data on gene expression have increased tremendously. The only way to analyze quantitatively and comprehensively such biological data is by developing and applying new sophisticated mathematical approaches. Here, we present extensions of 2D singular spectrum analysis (2D-SSA) for application to 2D and 3D datasets of embryo images. These extensions, circular and shaped 2D-SSA, are applied to gene expression in the nuclear layer just under the surface of the Drosophila (fruit fly) embryo. We consider the commonly used cylindrical projection of the ellipsoidal Drosophila embryo. We demonstrate how circular and shaped versions of 2D-SSA help to decompose expression data into identifiable components (such as trend and noise), as well as separating signals from different genes. Detection and improvement of under- and overcorrection in multichannel imaging is addressed, as well as the extraction and analysis of 3D features in 3D gene expression patterns., Peer-reviewed article, Published. Received 4 July 2014; Revised 10 September 2014; Accepted 10 September 2014.
Sharp borders from fuzzy gradients
Critical boundaries in the early Drosophila embryo are set by morphogenetic gradients. A new quantitative study shows that the placement of one such boundary is more accurate than the gradient thought to set it. Genetic analysis of the accuracy of the process implicates a gene not previously thought to be involved., Peer-reviewed article, Published.
Single-laboratory validation of a method for the detection and/or quantification of select alkaloids in goldenseal supplements and raw materials by reversed-phase high-performance liquid chromatography
Quality of botanical products and raw materials is important to manufacturers, regulators, researchers, and consumers. Many modern botanical quality-assurance schemes set specifications for select phytochemicals and measure against those specifications as one determinant of quality. While numerous publications describe procedures for determining compounds of interest in plant species, few methods have been systematically evaluated for accuracy, precision, or reliability, and often the analysis of finished products is not within the scope of the method. Hydrastis canadensis L., commonly referred to as Goldenseal, is an economically important North American medicinal plant that has been subject to adulteration in commerce. The phytochemicals of interest in the plant are the alkaloids hydrastine, berberine, and canadine. Of interest is also palmatine, an alkaloid found in potential adulterant species but not in goldenseal. In this study, goldenseal materials in raw, capsule, and tablet form, including an Echinacea/ Goldenseal combination product, were extracted with acidified water and acetonitrile and their hydrastine, berberine, canadine, and palmitine content determined by HPLC. The analytical method was optimized and evaluated in a single-laboratory validation study. Calibration curves for hydrastine and berberine were linear from 10 to 150 μ g/mL. The limits of detection for palmatine and canadine were determined to be 0.5 μ g/mL, which translates to detection of levels of 0.004% w/w in test samples. Chromatographic resolution was achieved for all analytes in an isocratic 12.5-min chromatographic run employing a binary mobile phase. Triplicate determinations performed on 10 test materials by two analysts on 3 days resulted in relative standard deviations ranging from 0.9% to 3.4%., Peer-reviewed article, Published.
The Smartphone Peer Physical Activity Counseling (SPPAC) program for manual wheelchair users
Physical activity (PA) must be performed regularly to accrue health benefits. However, the majority of manual wheelchair users do not meet PA recommendations. Existing community-based PA programs for manual wheelchair users appear to work, but effect sizes are small and retention is low. Existing PA programs may not fully implement some psychosocial factors that are strongly linked with PA (eg, autonomy). The use of peers and mobile phone technology in the Smartphone Peer PA Counseling (SPPAC) program represents a novel approach to cultivating a PA-supportive environment for manual wheelchair users., Peer-reviewed article, Published.
Spatial bistability generates hunchback expression sharpness in the drosophila embryo
During embryonic development, the positional information provided by concentration gradients of maternal factors directs pattern formation by providing spatially dependent cues for gene expression. In the fruit fly, Drosophila melanogaster, a classic example of this is the sharp on-off activation of the hunchback (hb) gene at midembryo, in response to local concentrations of the smooth anterior-posterior Bicoid (Bcd) gradient. The regulatory region for hb contains multiple binding sites for the Bcd protein as well as multiple binding sites for the Hb protein. Some previous studies have suggested that Bcd is sufficient for properly sharpened Hb expression, yet other evidence suggests a need for additional regulation. We experimentally quantified the dynamics of hb gene expression in flies that were wild-type, were mutant for hb self-regulation or Bcd binding, or contained an artificial promoter construct consisting of six Bcd and two Hb sites. In addition to these experiments, we developed a reaction-diffusion model of hb transcription, with Bcd cooperative binding and hb self-regulation, and used Zero Eigenvalue Analysis to look for multiple stationary states in the reaction network. Our model reproduces the hb developmental dynamics and correctly predicts the mutant patterns. Analysis of our model indicates that the Hb sharpness can be produced by spatial bistability, in which hb self-regulation produces two stable levels of expression. In the absence of self-regulation, the bistable behavior vanishes and Hb sharpness is disrupted. Bcd cooperative binding affects the position where bistability occurs but is not itself sufficient for a sharp Hb pattern. Our results show that the control of Hb sharpness and positioning, by hb self-regulation and Bcd cooperativity, respectively, are separate processes that can be altered independently. Our model, which matches the changes in Hb position and sharpness observed in different experiments, provides a theoretical framework for understanding the data and in particular indicates that spatial bistability can play a central role in threshold-dependent reading mechanisms of positional information., Peer-reviewed article, Published. Received October 16, 2007; Accepted August 13, 2008; Published September 26, 2008.
Spinal cord injury influences psychogenic as well as physical components of female sexual ability
Study Design: Secure, web-based survey. Objectives: Elicit specific information about sexual function from women with spinal cord injuries (SCI). Setting: World-wide web. Methods: Individuals 18 years or older living with SCI obtained a pass code to enter a secure website and then answered survey questions. Results: Bladder and/or bowel incontinence during sexual activity and/or sexual intercourse were significant concerns and prevented some women from seeking sexual activity. Autonomic dysreflexia (AD) during sexual activity was interpreted negatively by many and was found to interfere with sexual activity. Most subjects reported difficulty becoming psychologically aroused as well as physically aroused, which were both correlated with feeling that their SCI had altered their sexual sense of self. An inverse relationship existed between developing new areas of arousal above the level of lesion and not having sensation or movement below the lesion. The most commonly reported sexual stimulation leading to the best arousal involved stimulation of the head/neck and torso areas. The majority of subjects reported having experienced intercourse postinjury. Most participants reported difficulty with positioning during foreplay and intercourse, vaginal lubrication, and spasticity during intercourse. Almost half reported experiencing orgasm postinjury and this was positively associated with the presence of genital sensation. Conclusion: SCI significantly impairs psychological and physical aspects of female sexual arousal. In addition, bladder and bowel incontinence as well as AD negatively impact sexual activity and intercourse., Peer-reviewed article, Published.
Storage and the shift to low carbon energy
This work looks at the impact of assumptions made regarding efficiency of storage systems used with variable energy resources and how this applies to a solar PV installation. To find the optimal storage system to work with the cyclic solar output, a linear optimization model is implemented using OSeMOSYS. With 100% efficient, free storage, with no capacity restrictions, it is possible to get down to almost 5 GW of required solar installed capacity, but it requires 1.1 TWh of 100% efficient storage. Existing pumped hydro storage facilities have efficiencies between 70 and 80%, which increase these numbers to 7 GW and 1.2 TWh. With a storage model based on the worlds largest pumped hydro facility between 20 and 25 GW of installed solar capacity are required plus between 15 and 30 GWh of storage capacity to meet the 1 GW load. The capital infrastructure required to allow a solar installation to meet that of a baseload plant is therefore around an order of magnitude larger than what is commonly assumed. A shift away from fossil fuels to renewable/variable energy resources will require more infrastructure than indicated by simply considering the capacity factor of the energy source., Peer-reviewed article, Published. Manuscript received September 30, 2014; revised January 18, 2015.
Suppression of positional errors in biological development
Cells in developing embryos behave according to their positions in the organism, and therefore seem to be receiving `positional information'. A widespread view of the mechanism for this is that each cell responds locally to the concentration level of some extracellular chemical which is distributed in a spatial gradient. For molecules conveying and receiving the positional signal, concentrations are likely to be low enough that, per individual cell, only a few thousand molecules may be involved. Fluctuations to be expected in these numbers (Poisson distribution) could readily lead to errors up to a few percent of embryo length in the reading of position. This is an intolerable level of error for some developmental pattern-forming events. Embryos must have means of suppressing such errors. We maintain that this requires communication between cells, and illustrate this by using the reaction part of two well-known Turing-type reaction–diffusion models as the local gradient reader. We show that switching on diffusion in these models leads to adequate suppression of positional errors., Peer-reviewed article, Published. Received 31 December 1997, Revised 20 July 1998, Accepted 21 July 1998, Available online 24 March 1999.
Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates
Several molecules inhibit axonal growth cones and may account for the failure of central nervous system regeneration, including myelin proteins and various chondroitan sulfate proteoglycans expressed at the site of injury. Axonal growth inhibition by myelin and chondroitan sulfate proteoglycans may in part be controlled by Rho-GTPase, which mediates growth cone collapse. Here, we tested in vitro whether pharmacological inhibition of a major downstream effector of Rho, Rho-kinase, promotes axonal outgrowth from dorsal root ganglia grown on aggrecan. Aggrecan substrates stimulated Rho activity and were inhibitory to axonal growth. Y-27632 treatment promoted the growth of axons by 5- to 10-fold and induced “steamlined” growth cones with longer filopodia and smaller lamellipodia. Interestingly, more actin bundles reminiscent of stress fibers in the central domain of the growth cone were observed when grown on aggrecan compared to laminin. In addition, Y-27632 significantly promoted axonal growth on both myelin and adult rat spinal cord cryosections. Our data suggest that suppression of Rho-kinase activity may enhance axonal regeneration in the central nervous system., Peer-reviewed article, Published. Received 2 July 2002; Revised 24 October 2002; Accepted 28 October 2002; Available online 23 March 2003.
Synthesis of galactofuranosyl-containing oligosaccharides corresponding to the glycosylinositolphospholipid of Trypanosomacruzi
The oligosaccharide β-d-Galf-(1→3)-α-d-Manp-(1→2)-[β-d-Galf-(1→3)]-α-d-Manp-(1→2)-α-d-Manp corresponds to the terminal end of the glycosylinositolphospholipid oligosaccharide of the protozoan Trypanosomacruzi, the causative agent of Chagas’ disease. Syntheses of methyl or ethylthio glycosides of the terminal disaccharide, trisaccharide, tetrasaccharide, and pentasaccharide corresponding to this structure are described. These syntheses employ the selective activation of a phenyl 1-selenogalactofuranoside or a phenyl 1-selenomannopyranoside donor over ethyl 1-thioglycoside acceptors with NIS–TfOH., Peer-reviewed article, Published. Received 8 December 1999; Accepted 14 December 1999; Available online 19 April 2000.

Pages