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Introduction
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Publications (69)
Carrying out research means being innovative, which requires novelty. Novelty is an important source of scientific breakthroughs and has great technological impact. Research institutions stand to benefit from fostering innovation. Here, we outline what academic institutions can do to help their scientists become more innovative.
Purpose:
We previously identified three microRNAs (miRNAs) with significantly increased expression in the serum of patients with age-related macular degeneration (AMD) compared with healthy controls. Our objective was to identify potential functional roles of these upregulated miRNAs (miR-19a, miR-126, and miR-410) in AMD, using computational tool...
Introduction
An understanding of how dentists develop patient support techniques for use with adults with intellectual developmental disorders (IDD) may lead to a better understanding of how these techniques can be taught. In this study we explored how skilled dentists developed non‐physical, non‐pharmacological patient support techniques (nPSTs) f...
Purpose:
To identify circulating microRNAs (miRNA) associated with age-related macular degeneration (AMD). Thus differentially expressed serum miRNA could be used as AMD biomarkers.
Methods:
This study involved total RNA isolation from sera from patients with atrophic AMD (n = 10), neovascular AMD (n = 10), and age- and sex-matched controls (n =...
As scientific research has advanced so too has the complexity of the questions addressed. Cross‐disciplinary collaborations are often the most efficient route to managing that complexity and require effective communication across boundaries. To continue driving science forward and be able to tackle global challenges, the art of good interdisciplina...
This essay argues how practical spirituality involves the art and science of conscious living. Conscious living involves silencing the continuous chatter of the mind in a relaxed playful manner and looking within to connect with what is going inside us. At the same time being in touch with what is happening outside. Then putting together both these...
A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence...
Survivin (Birc5) is the smallest member of the inhibitor of apoptosis (IAP) protein family, which regulates the cell cycle/apoptosis balance. The purpose of this study was to examine Survivin expression in the embryonic chick lens, in chick lens epithelial cell cultures, and in the postnatal mouse lens.
Survivin expression was examined using a comb...
Hirschsprung's disease is characterised by the absence of ganglion cells in the distal bowel, a process which is controlled by complex genetic pathways. Homeobox genes have a major role in gut development and this is depicted by the enteric Hox code which describes the different spatial and temporal expression of Hox genes. Hoxa9 and Hoxa13 mutatio...
To investigate the developmental and ocular expression of Opa3 in a mouse model of 3-methylglutaconicaciduria type III and the effect of mutation on protein localization and mitochondrial morphology.
The B6 C3-Opa3(L122P) mouse carrying a missense mutation in exon 2 (c.365T>C; p.L122P) of Opa3, which displays features of recessive 3-methylglutaconi...
Millions are rendered blind or exhibit visual impairment due to pathologies of the lens of the eye. Lens research therefore addresses the direct need to gain insights into the cellular and molecular basis of disease, but, moreover, serves as a valuable experimental system to answer fundamental biological questions. This themed issue showcases the s...
The programmed removal of organelles from differentiating lens fibre cells contributes towards lens transparency through formation of an organelle-free zone (OFZ). Disruptions in OFZ formation are accompanied by the persistence of organelles in lens fibre cells and can contribute towards cataract. A great deal of work has gone into elucidating the...
In the present paper, gene expression analysis of mouse embryonic stem (ES) cells levitated in a novel ultrasound standing wave trap (USWT) (Bazou et al. 2005a) at variable acoustic pressures (0.08-0.85 MPa) and times (5-60 min) was performed. Our results showed that levitation of ES cells at the highest employed acoustic pressure for 60 min does n...
Apoptosis, is the main type of cell death that occurs in ageing and neurodegenerative disease, such as glaucoma. This study therefore characterises the expression profile of caspases (pro-apoptosis) and inhibitors of apoptosis (IAPs; anti-apoptosis) during maturation of the Brown Norway rat retina between 6 weeks and >24 weeks and also examines con...
Recently, the zebrafish (Danio rerio) has been shown to be an excellent model for human paediatric research. Advantages over other models include its small size, externally visually accessible development and ease of experimental manipulation. The enteric nervous system (ENS) consists of neurons and enteric glia. Glial cells permit cell bodies and...
Glaucoma is characterised by the preferential death of retinal ganglion cells (RGCs). However, mammalian models indicate that neurons pass through a period in which they manifest signs of neuronal damage, but have yet to fully commit to death. Mounting evidence suggests that one of the clearest indications of this process is the reduction in RGC de...
Evidence is emerging for apoptosis gene expression in the lens during development. Therefore, here we used a filter array to assess expression of 243 apoptosis-related genes in the developing postnatal mouse lens using (33)P labelled cDNA synthesized from p7 and p14 mouse lenses. We demonstrated that 161 apoptosis-related genes were expressed at le...
Magnetic resonance imaging (MRI) is a powerful tool for generating 3-dimensional structural and functional image data. MRI has already proven valuable in creating atlases of mouse and quail development. Here, we have exploited high resolution MRI to determine the parameters necessary to acquire images of the chick embryo eye. Using a 9.4 Tesla (400...
Phosphoimage of an array hybridised with P7 radiolabelled RNA. Examples of positive spots are provided, including genomic DNA spots for orientation of the array as well as housekeeping genes and apoptosis genes (caspase-7 and 14-3-3 eta).
Reproducibility of array results. Scatter plots (A–E) were produced by plotting the normalised signal intensities from one array against another. Array results were compared between arrays that had been treated identically (i.e. fresh array compared with a fresh array, or a stripped array compared with a stripped array) or that had been treated dif...
Graphical representations of representative Western blots using densitometry normalised against the actin control at each stage examined for chick Mdm2, Mdm4/X and p53. Error bars represent standard deviation of the mean for a minimum of 3 replicates in each case. (A) The Mdm2-positive band at 55 kDa was faint at embryonic day (ED)6-ED8, peaked in...
RT-PCRs reveal expression of Mdm2, Mdm4/X and p53 during embryonic stages of mouse lens development. PCRs were also carried out on cDNA prepared as described in Materials and Methods from E12.5 pooled mouse embryo whole eyes and on pooled lenses from E14.5, E16.5 as well as the post-natal stages examined previously. All three genes were differentia...
Graphical representations of representative Western blots using densitometry normalised against the actin control at each stage examined for mouse Mdm2, Mdm4/X and p53. Error bars represent standard deviation of the mean for a minimum of 3 replicates in each case. (A) Mdm2 expression at approximately 55 kDa was detected in the Nb lens, peaked at p7...
Standard curves for semi-quantitative PCR of chicken embryo lens. Standard curves were completed for three genes expressed at relatively high (GAPDH), intermediate (13-3-3 eta) and low levels (Mdm2) to determine the number of cycles to be used to ensure the PCR was in the linear phase of the reaction. The increase in band intensity with increasing...
Graphical representations of representative Western blots using densitometry normalised against the actin control at each stage examined for mouse Axl-1 and Mcl-1. Error bars represent standard deviation of the mean for a minimum of 3 replicates in each case. (A) Axl expression peaked at Nb and had a constant low level of expression thereafter to 4...
Understanding the mechanisms controlling stem cell differentiation is the key to future advances in tissue and organ regeneration. Embryonic stem (ES) cell differentiation can be triggered by embryoid body (EB) formation, which involves ES cell aggregation in suspension. EB growth in the absence of leukaemia inhibitory factor (LIF) leads EBs to mim...
This table lists names and primer sequences of genes that were identified by both array experiments, but not confirmed.
Q-PCR confirmation of expression patterns of Hspa8 and BG063737 and comparison with semi-quantitative PCR results. Q-PCR confirmation of expression patterns of Hspa8 and BG063737 and comparison with semi-quantitative PCR results. Q-PCR was carried out using an MJ-Research Peltier Thermal Cycler PTC-200 PCR machine and results were analysed using MJ...
Purpose Evidence is emerging for haemoglobin (Hb) expression outside the vascular system. We previously demonstrated Hb expression in the mouse lens during post‐natal development and cataract progression. Here, we extended this work by carrying out a comprehensive spatio‐temporal analysis of Hb subunit expression during mouse lens development and m...
Expectations of entry-level students at a traditional research-led UK university were
compared to staff perceptions of student attitudes. Questionnaires were organised around five
themes: factors affecting choice of degree scheme; proficiency in key-skills; effectiveness of
teaching methods; effectiveness of assessment methods; and usefulness of ed...
Opa3 mRNA is expressed in all tissues examined to date, but currently the function of the OPA3 protein is unknown. Intriguingly, various mutations in the OPA3 gene lead to two similar diseases in humans: autosomal dominant inherited optic atrophy and cataract (ADOAC) and a metabolic condition; type 3-methylglutaconic aciduria (MGA). Early onset bil...
We investigated the spatio-temporal profile of hemoglobin subunit expression in developing avascular tissues. Significant up-regulation of hemoglobin subunits was identified in microarray experiments comparing blastocyst inner cell masses with undifferentiated embryonic stem (ES) cells. Hemoglobin expression changes were confirmed using embryoid bo...
DefinitionThe 5 region of the mRNA that is not translated into protein. It extends from the transcription start site to the translation ATG start site, and contains regulatory sequences that control mRNA stability and translation efficiency.
Proteases have important roles in development and in disease. Here, the recent literature pertaining to the role of proteases in lens development (including lens fiber cell organelle loss) and cataract progression is reviewed. Families of proteases reviewed include caspases, calpains, cathepsins, the ubiquitin proteasome pathway and matrix metallop...
The eye is one of the classical systems in developmental biology. Furthermore, diseases of the eye, many of which have a developmental basis, have devastating effects that often result in blindness. Proteases have diverse roles in ocular physiology and pathophysiology. Here, a broad overview is provided of the recent literature pertaining to the in...
Sparc/osteonectin is a hydroxyapatite, calcium and, collagen binding protein, implicated in tissue morphogenesis, cell proliferation, and repair. Sparc null mice develop sub-cortical posterior cataract with eventual rupture of the lens. We wished to correlate genotype with phenotype in these mice via analysis of gene expression pattern changes lead...
Defects in the development and physiology of the lens can result in cataracts (opacification of the lens), which are currently treatable only by surgical removal. The lens is also an excellent system for understanding fundamental biological processes such as cellular differentiation and ageing. Here, microarrays have been used to gain insights into...
The Rancourt EST Database (RED) is a web-based system for the analysis, management, and dissemination of expressed sequence tags (ESTs). RED represents a flexible template DNA sequence database that can be easily manipulated to suit the needs of other laboratories undertaking mid-size sequencing projects.
Availability: http://www.ucalgary.ca/~ranco...
Zinc finger transcription factors play essential roles in neural crest cell development. Even subtle disruptions of the function of these genes could contribute significantly to complex developmental phenotypes such as the multigenic disorder Hirschsprung disease (HSCR), a congenital failure of enteric neurogenesis. Although germline mutations in t...
Transcription factors play important roles in development and homeostasis. We have completed an embryonic stem cell-based neural differentiation screen, which was carried out with a view to isolating early regulators of neurogenesis. Fifty eight of the expressed sequence tags isolated from this screen represent known transcription factors or sequen...
We have used a method for synchronously differentiating murine embryonic stem (ES) cells into functional neurons and glia in culture. Using subtractive hybridization we isolated approximately 1200 cDNA clones from ES cell cultures at the neural precursor stage of neural differentiation. Pilot studies indicated that this library is a good source of...
The lens represents an ideal model system for studying many of the cellular and molecular events of differentiation. It is composed of two ectodermally-derived cell types: the lens epithelial cells and the lens fibre cells, which are derived from the lens epithelial cells by differentiation. Programmed removal of nuclei and other organelles from th...
Neurodegenerative diseases cost the economies of the developed world billions of dollars per annum. Given ageing population profiles and the increasing extent of this problem, there has been a surge of interest in neural stem cells and in neural differentiation protocols that yield neural cells for therapeutic transplantation. Due to the oncogenic...
The optical clarity of the lens is ensured by the programmed removal of nuclei and other organelles from the lens fibre cells during development. The morphology of the degenerating nuclei is similar to that observed during apoptosis and is accompanied by DNA fragmentation. Proteins encoded by the bcl-2 proto-oncogene family are important in either...
DNA fragmentation in lens fibre cell nuclei undergoing programmed degeneration was identified by terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL). Lens epithelial cells in culture were induced to differentiate into lens fibre-like clumps of cells (lentoids) by insulin and it was shown that the TUNEL method...
We have examined the expression of TNF-alpha and its receptors, TNFR1 and TNFR2, during gastrulation in the chick embryo, and have investigated the possible role of this factor in the control of cell death at this early stage of development. TNF-alpha, immunoreactive at approximately 17 kD, was found both in vivo and in vitro, most intensely associ...
We review the evidence for a role for transforming growth factor-beta (TGF-beta) and for tumor necrosis factor-alpha (TNF-alpha) in the development of the avian embryo. Transforming growth factor-beta is expressed in a number of locations in the early embryo with a distribution consistent with a function in epithelial-mesenchymal transformation and...
In this paper, the more recent literature pertaining to differentiation in the developing vertebrate lens is reviewed in relation to previous work. The literature reviewed reveals that the developing lens has been, and will continue to be, a useful model system for the examination of many fundamental processes occurring during embryonic development...
We describe an ultrastructural adaptation of the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) for the identification of DNA fragmentation. Thin sections of tissue embedded in hydrophilic resin were nick end labelled with biotinylated dUTP which was subsequently labelled with avidin conjugated to go...
Thesis (Ph. D.)--University of Alberta, Spring 1996. Includes bibliographical references (leaves 46-73, 84-92, 123-128, 153-157, 191-208, 246-248, 262-266). Photocopy.
Although cell death has long been recognized to be a significant element in the process of embryonic morphogenesis, its relationships to differentiation and its mechanisms are only now becoming apparent. This new appreciation has come about not only through advances in the understanding of cell death in parallel immunological and pathological situa...
This paper reviews the evidence indicating possible roles for tumour necrosis factor-alpha (TNF alpha) in development. It is proposed that TNF alpha may have essentially three major roles during embryonic development, which may be analogous to its roles in the immune system and during inflammation: a role in programmed cell death; a role as a cellu...
Early chick embryos have previously been shown to express tumor necrosis factor-alpha-cross-reactive proteins (TNF alpha-CRPs) in a developmentally regulated manner, thus implicating these proteins in programmed cell death and in tissue remodeling. In this study, cells undergoing DNA fragmentation have been identified, using terminal deoxynucleotid...
We have used an antibody against a TGF beta peptide fragment to localize this growth factor in the early chick embryo from laying to the ten-somite stage of development. Western blotting showed that the antibody reacted with both mammalian TGF beta 1 and chicken TGF beta 3. By immunocytochemistry we find that at the earliest developmental stage (st...
We have investigated the expression of tumor necrosis factor-alpha (TNF alpha)-cross-reactive proteins during the early development of the chick embryo from day 1 to day 6 (H-H stages 5-29) using a polyclonal antibody and two monoclonal antibodies to recombinant mouse TNF alpha. We have confirmed the cross-reactivity of the antibodies with chicken...
Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a hi...
Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a hi...