PubMed Health⌕ Search

Biomedical subjects

Paul O'Neill

Publications and source records attributed to Paul O'Neill.

6 recordsLinked to original sources
PubMed2004

Nogo and Nogo-66 receptor in human and chick: implications for development and regeneration.

Antibodies to the myelin protein Nogo increase axonal regrowth after central nervous system injury. We have investigated whether Nogo expression contributes to loss of regenerative potential during development by using chick embryos, which regenerate their spinal cord until embryonic day (E) 13, when myelination begins. We show that Nogo-A and the Nogo receptor (NgR) are developmentally regulated both in chick and human embryos, are first detected at developmental stages when the chick spinal cord regenerates, and are not down-regulated after injury at permissive stages for regeneration. Therefore, expression of Nogo-A and NgR in pre-E13 chick spinal cords is not sufficient to inhibit regeneration. Nogo-A expression in the chick early embryo is primarily observed in axons, whereas NgR is mainly located on neuronal cell bodies, both in spinal cord and eye, and in striated muscle including the heart. With the onset of myelination, there is down-regulation of Nogo-A expression in neurons. Therefore, loss of regenerative potential might be linked to changes in its cellular localization. The possibility that only Nogo expressed in mature oligodendrocytes can exercise inhibitory effects would reconcile the lack of inhibition we observe in developing chick spinal cords before the onset of myelination with evidence from other laboratories on the inhibitory effects of Nogo in mature central nervous system. The distinctive and complementary patterns of Nogo-A and NgR expression and their conservation throughout evolution support the view that Nogo signaling represents a key pathway in nervous system and striated muscle development. Its putative role in target innervation and establishment of neural circuitry is discussed.

Amino Acid Sequence↗
PubMed2003

Changes in spinal cord regenerative ability through phylogenesis and development: lessons to be learnt.

Lower vertebrates, such as fish and amphibians, and developing higher vertebrates can regenerate complex body structures, including significant portions of their central nervous system. It is still poorly understood why this potential is lost with evolution and development and becomes very limited in adult mammals. In this review, we will discuss the current knowledge on the cellular and molecular changes after spinal cord injury in adult tailed amphibians, where regeneration does take place, and in developing chick and mammalian embryos at different developmental stages. We will focus on the recruitment of progenitor cells to repair the damage and discuss possible roles of changes in early response to injury, such as cell death by apoptosis, and of myelin-associated proteins, such as Nogo, in the transition between regeneration-competent and regeneration-incompetent stages of development. A better understanding of the mechanisms underlying spontaneous regeneration of the spinal cord in vivo in amphibians and in the chick embryo will help to devise strategies for restoring function to damaged or diseased nervous tissues in mammals.

Animals↗
PubMed2003

Improved processing of microarray data using image reconstruction techniques.

Spotted cDNA microarray data analysis suffers from various problems such as noise from a variety of sources, missing data, inconsistency, and, of course, the presence of outliers. This paper introduces a new method that dramatically reduces the noise when processing the original image data. The proposed approach recreates the microarray slide image, as it would have been with all the genes removed. By subtracting this background recreation from the original, the gene ratios can be calculated with more precision and less influence from outliers and other artifacts that would normally make the analysis of this data more difficult. The new technique is also beneficial, as it does not rely on the accurate fitting of a region to each gene, with its only requirement being an approximate coordinate. In experiments conducted, the new method was tested against one of the mainstream methods of processing spotted microarray images. Our method is shown to produce much less variation in gene measurements. This evidence is supported by clustering results that show a marked improvement in accuracy.

Algorithms↗
PubMed2002

Building confidence for work as house officers: student experience in the final year of a new problem-based curriculum.

INTRODUCTION: Newly qualified doctors require an appropriate level of confidence for their new roles. Development of this confidence was a key objective in the final year of a new integrated course with an emphasis on student self-direction. CONTEXT: There are 5 placements in the final year course. Students use a Learning Planner to help them choose suitable placements and objectives to serve their learning needs. Educational supervision focuses on helping students determine their objectives and assessing them against these. METHODS: Course evaluation was by means of a questionnaire during final assessments. Cohorts of 310 and 316 students in successive years completed the evaluation. The interrelationship between variables was explored using logistic regression. RESULTS: 220/310 students in the 2000 cohort and 214/316 in the 2001 cohort agreed they felt confident with their prospective role as a pre-registration house officer (PRHO). Confidence was significantly associated with confidence in their clinical skills, belief in their ability to cope with uncertainty and feeling able to work as a team member. The experience of the 2 hospital placements and (in 2000 only) the elective was associated with increased confidence. In all placements helpful educational supervision and the achievement of the self-directed learning plan was associated with increased confidence as a potential doctor. CONCLUSION: Students perceive a relationship between learning experiences in the final year of a self-directed course and development of confidence for their future role. Whilst further elucidation of the nature of this relationship is required, this provides encouragement to curriculum planners to promote self-direction.

Clinical Competence↗