Publications by authors named "Colin Sharpe"

Fish have been highly exposed to radiation in freshwater systems after the Chernobyl Nuclear Power Plant (NPP) accident in 1986 and in freshwater and marine systems after the more recent Fukushima NPP accident in 2011. In the years after the accident, the radioactivity levels rapidly declined due to radioactive decay and environmental processes, but chronic lower dose exposures persisted. To gain insights into the long-term effects of environmental low dose radiation on fish ovaries development, a high-throughput transcriptomic approach including a de novo assembly was applied to different gonad phenotypes of female perch: developed gonads from reference lakes, developed/irradiated from medium contaminated lake, and both developed/irradiated and undeveloped from more highly contaminated lakes.

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The Chernobyl and Fukushima nuclear power plant (NPP) accidents that occurred in 1986 and 2011 respectively have led to many years of chronic radiation exposure of wildlife. However, controversies remain on the dose threshold above which an impact on animal health occurs. Fish have been highly exposed immediately after both accidents in freshwater systems around Chernobyl and in freshwater and marine systems around Fukushima.

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Organismal complexity broadly relates to the number of different cell types within an organism and generally increases across a phylogeny. Whilst gene expression will underpin organismal complexity, it has long been clear that a simple count of gene number is not a sufficient explanation. In this paper, we use open-access information from the Ensembl databases to quantify the functional diversity of human genes that are broadly involved in transcription.

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Vertebrate NCoR-family co-repressors play central roles in the timing of embryo and stem cell differentiation by repressing the activity of a range of transcription factors. They interact with nuclear receptors using short linear motifs (SLiMs) termed co-repressor for nuclear receptor (CoRNR) boxes. Here, we identify the pathway leading to increasing co-repressor diversity across the deuterostomes.

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Pax7 expressing muscle stem cells accompany all skeletal muscles in the body and in healthy individuals, efficiently repair muscle after injury. Currently, the in vitro manipulation and culture of these cells is still in its infancy, yet muscle stem cells may be the most promising route toward the therapy of muscle diseases such as muscular dystrophies. It is often overlooked that muscular dystrophies affect head and body skeletal muscle differently.

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The vertebrate head-trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors.

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Background: Despite strong laboratory evidence that non-steroidal anti-inflammatory drugs (NSAIDs) could prevent prostate cancer, epidemiological studies have so far reported conflicting results. Most studies were limited by lack of information on dosage and duration of use of the different classes of NSAIDs.

Methods: We conducted a nested case-control study using data from Saskatchewan Prescription Drug Plan (SPDP) and Cancer Registry to examine the effects of dose and duration of use of five classes of NSAIDs on prostate cancer risk.

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Article Synopsis
  • Small molecules like retinoic acid use heterodimers of nuclear receptors and RXR to regulate gene expression by binding to DNA and acting as transcription factors.
  • In the absence of signals, these receptors associate with co-repressors like SMRT and NCoR to inhibit gene activity.
  • The study reveals that different isoforms of SMRT, generated through alternative splicing, play distinct roles in interacting with nuclear receptors, enhancing the complexity of gene regulation in cells.
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The corepressor SMRT acts on a range of transcription factors, including the retinoid and thyroid hormone nuclear receptors. The carboxy-terminal region of SMRT contains CoRNR box motifs that mediate these interactions. We have shown, in Xenopus, that SMRT can exist as isoforms containing either two or three CoRNR boxes depending on the alternative splicing of exon 37b.

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Purpose: The present study examined the developmental and tissue expression of the retinitis pigmentosa GTPase regulator (RPGR) gene in Xenopus laevis.

Methods: The cDNA for X. laevis RPGR (XRPGR) was isolated from adult eye mRNA by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends.

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The neurexins are involved in the formation and function of synapses. Each of three genes encodes alpha- and beta-neurexins. Additional diversity (particularly of alpha-neurexins) arises from alternative splicing, resulting in a large number of protein isoforms, the significance of which is currently unclear.

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SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box.

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Silencing mediator for retinoid and thyroid hormone receptor (SMRT) and nuclear receptor corepressor protein (NCoR) are corepressors that interact with a range of transcription factors. They both consist of N-terminal repressor domains that associate with histone deacetylases and C-terminal interaction domains (IDs) that contain CoRNR box motifs. These motifs mediate the interaction between corepressors and nuclear receptors (NRs), such as the retinoid and thyroid hormone receptors.

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Purpose: The aim of this study was to assess the effects of smoking on the risk of colorectal cancer according to anatomic subsite.

Methods: Between 1979 and 1985 a population-based case-control study of cancer at multiple sites was performed in Montréal, which accrued over 4,000 males in total, including cases of colorectal cancer, other cancers, and population controls. The present analysis was restricted to the 585 cases with histologically proven adenocarcinoma of the large bowel, aged 35 to 70 years, who underwent face-to-face interviews and provided adequate smoking histories.

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Objective: To estimate the effects of alcohol consumption on the risk of colorectal cancer according to anatomical subsite.

Methods: Between 1979 and 1985 a population-based case-control study of cancer at multiple sites was carried out in Montreal. This analysis was restricted to the 585 cases with adenocarcinoma of the large bowel, aged 35-70 years, who underwent face-to-face interviews.

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